Matus-Ortega, Romero-Aguilar, González, Guerra Sánchez, Matus-Ortega, Castillo-Falconi, and Pardo: The Randle cycle, the precarious link between sugars and fats



Introduction

In accordance with data from the World Health Organization (WHO), diseases associated with obesity have become one of the main health problems worldwide. The number of overweight people in almost every region of the world (except in certain sub-Saharan African regions and some Asian areas) has been increasing at a constant annual rate of 0.7% since 1975 to the end of the second decade of the 21st century (World Health Organization, 2018) Using the body mass index (BMI) scale, the WHO pointed out that in 2016, more than 39% of people older than 18 years old (more than 1,900 million) were overweight, while 13% of the world’s population (more than 650 million people) was diagnosed with obesity. Among children and teenagers within the age interval of 5-19 years and children under 5 years old, 18% (over 340 million) and 6% (more than 113 million children) were overweight, respectively (Murray, 2019; Pearlman, Obert & Casey, 2017; Stanhope, 2016) . This worldwide phenomenon in which there are more overweight than underweight people was recognized since the last third of the 20th century, indicating that two out of the three countries in North America (namely, México and the United States), and many countries of the European Union, had the most affected population by this health crisis (Hruby & Hu, 2015; Ogden, Yanovski, Carroll & Flegal, 2007; Pereira et al., 2020; Smith & Smith, 2016).

It is generally stated that the main cause of obesity is related to an imbalance between the calories consumed and the calories expended. In accordance with WHO experts (World Health Organization, 2018), obesity problems can be explained considering that “there is an increased intake of energy-dense foods that are high in fat, along with an increase in physical inactivity due to the increasingly sedentary nature of many forms of work, changing modes of transportation, and increasing urbanization”.

However, to prevent and treat the obesity problem, experts need to clearly understand lipogenesis and lipolysis, as well as the processes that determine the formation of adipose tissue derived from both sugar-rich foods, whose main ingredient is fructose, and foods high in fat (Moran & Ladenheim, 2016; Priyadarshini & Anuradha, 2017). In other words, it is essential to understand the glucose-fatty acid cycle, also known as the Randle cycle, to recognize the causes of obesity and propose preventive and effective measures (Randle, Garland, Hales & Newsholme, 1963).

Likewise, the general population should be aware of the seventy different names given to sugar that are included in processed foods, in order to keep track of excessive carbohydrate consumption (Gómez Candela & Palma Milla, 2013; Rodríguez Delgado, 2017). It is estimated that sugar-sweetened beverages (soft drinks, juices, nectars, teas, energy drinks, yogurts, among others) are the main sources of sugar in the diet, accounting for more than 15% of the daily caloric intake. Besides, many people do not even realize that their consumption of sugar-sweetened beverages and low-nutrient density foods is much more frequent than they think (Jensen et al., 2018; Rodríguez Delgado, 2017).

This increase in sugar consumption has been associated with pathologies such as liver steatosis, type 2 diabetes mellitus, simple and combined hyperlipidemias (hypertriglyceridemia and hypercholesterolemia), cardiovascular diseases (hypertension, and heart failure) and dental caries, the latter originally described as the only disorder due to sugar consumption. Therefore, in this review we updated the information regarding the Randle cycle, proposed in 1963 (Randle et al., 1963), and the balance between the formation of acylglycerols and their breakdown (lipogenesis/lipolysis).

The Randle cycle and its association with the balance between lipogenesis and lipolysis

Postprandial state

Under hyperglycemic conditions, such as the postprandial state, insulin induces an increase in the expression of glycolytic regulatory enzymes (glucokinase; phosphofructokinase 1, PFK-1; and pyruvate kinase) and the glucose transporter GLUT 4 (Figure 1). Insulin also activates genes that code for enzymes involved in the Randle cycle (Table I), leading to an increase in the glycolytic and Krebs cycle fluxes and the stimulation of anabolic pathways, such as lipogenesis, β-reduction [synthesis of fatty acids in the cytosol catalyzed by the Fatty Acid Synthase (FAS)], phospholipogenesis and cholesterogenesis (Marcelino et al., 2013; Nakamura, Yudell & Loor, 2014; Palomer, Salvado, Barroso & Vázquez-Carrera, 2013; Possik, Madiraju & Prentki, 2017).

Figure 1

Metabolic pathways involved in the extended Randle cycle. Abbreviations: GK: Glucokinase; PFK-1: Phosphofructokinase-1; PK: Pyruvate Kinase; PDC: Pyruvate Dehydrogenase Complex; PEPCK: Phosphoenolpyruvate Carboxykinase; PCmt: mitochondrial Pyruvate Carboxylase; ACC: Acetyl-CoA Carboxylase; HMGCoA reductase: Hydroxymethylglutaryl-CoA reductase; acyl-ACP: acyl-acyl-carrier protein; LPL: Lipoprotein Lipase; HSL: Hormone-Sensitive Lipase; CAT1: Carnitine Acyltransferase 1; Chol: Cholesterol; TAG: Triacylglycerol; DAG: Diacylglycerol; FABP: Fatty Acid Binding Protein; FATP: Fatty Acid Transporter Protein; FAT/CD36: Fatty Acid Transporter. Enzymes and pathways stimulated by insulin are highlighted in black; enzymes and pathways activated by glucagon and norepinephrine are highlighted in blue. Black boxes without color frames indicate enzymes whose overexpression increases in the postprandial state; blue boxes indicate enzymes up-regulated by fasting (glucagon and epinephrine). Black boxes with yellow frames indicate the main pathways promoted in the postprandial state. Blue boxes with a green frame highlight the main pathways activated during hypoglycemia resulting from fasting. * Reactions that take place in the mitochondrial matrix. Modified from Nelson & Cox, 2017; Aguilar et al. 2017.

1405-888X-tip-23-e270-gf1.png

Table I

Enzymes involved in the Randle cycle. Insulin increases the entry of glucose into the cells, the rate of glycolysis, the pentose phosphate pathway, as well as some anabolic pathways that are fed by the carbon skeletons derived from glucose. Some examples concerning these pathways are β-reduction and lipogenesis. Modified from Nelson & Cox, 2017.

Increased expression Metabolic pathway
Hexokinase II Glycolysis
Hexokinase IV Glycolysis
Phosphofructokinase-1 Glycolysis
Pyruvate kinase Glycolysis
Phosphofructokinase-2/Fructose-2,6-bisphosphatase Glycolysis/gluconeogenesis regulation
Glucose 6-phosphate dehydrogenase Phosphopentose pathway
6-phosphogluconate dehydrogenase Phosphopentose pathway
Pyruvate dehydrogenase complex Krebs cycle entry
Acetil-CoA carboxylase β-reduction
Malic enzyme β-reduction
Citrate lyase cytosolic β-reduction
Fatty acid synthase β-reduction
Acyl-CoA-glycerol transferase Lipogenesis
Decreased expression Metabolic pathway
Phosphoenolpyruvate carboxykinase Gluconeogenesis
Glucose 6-phosphatase Glycemic regulation

In terms of metabolic pathways, it can be inferred that a sugar overload in glycolysis will drive some of the glucose carbons towards dihydroxyacetone phosphate (DHAP) (Figure 1), which is involved in the formation of acylglycerols (lipogenesis) and phospholipids (phospholipogenesis) (Song, Xiaoli & Yang, 2018) (Figure 1). Therefore, glycolytic flux and anaplerotic pathways are activated in the presence of insulin (Ameer, Scandiuzzi, Hasnain, Kalbacher, & Zaidi, 2014; Bartelt et al., 2013; Summermatter et al., 2009).

Carbon overload in glycolysis is also associated with the transfer of citrate from mitochondria to the cytosol, where oxaloacetate (OAA) and acetyl-CoA are produced by the ATP citrate lyase (Figure 1). The first of these metabolites can be reduced or transaminated and returned to the mitochondrial matrix, forming part of the malate-aspartate shuttle.

Acetyl-CoA can take two pathways in the cytosol: the formation of fatty acids or the synthesis of cholesterol (Figure 1). Fatty acid formation is controlled by the FAS and the presence of allosteric regulators of the acetyl-CoA carboxylase (ACC) (Figure 1). In the presence of insulin, β-oxidation (the mitochondrial catabolic process of breaking down fatty acids) is inhibited by malonyl-CoA, stopping the transport of fatty acids into the mitochondrial matrix mediated by the fatty acid transporter Carnitine Acyltransferase 1 (CAT1) (Figure 1).

Regarding cholesterol formation, the pathway is regulated by the hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase). The fate of acetyl-CoA’s carbons can be defined as tissue-dependent, and regulated by the formation of malonyl-CoA and mevalonate metabolites, which control the rate of β-reduction and cholesterogenesis, respectively (Barbosa & Siniossoglou, 2017; Kory, Farese Jr. & Walther, 2016; Mottillo et al., 2014; Rambold, Cohen & Lippincott-Schwartz, 2015).

Insulin also increases the expression of lipoprotein lipase (LPL) in the postprandial state. This allows the hydrolysis of plasma triacylglycerol (TAG) from exogenous sources (diet), found in chylomicrons, and endogenous sources (hepatic), present in the Very Low Density Lipoproteins (VLDL) (Figure 1). Proper LPL functioning is associated with adapter proteins that stabilize and activate LPL (Quiroga & Lehner, 2012), such as apoprotein C-II on the smooth and skeletal muscles, and adipose tissue (Figure 1). Also, hydrolysis of TAG is more efficient when apoprotein C-V is active.

Fasting conditions

Under fasting or starvation conditions, lipolysis in white adipocytes is increased by hormones, such as glucagon (Pereira et al., 2020) and norepinephrine, which activate the hormone-sensitive lipase (Figure 1), and decrease the activity of the enzymes that control lipid anabolism, such as HMG-CoA reductase, ACC, and LPL (Hilton, Karpe & Pinnick, 2015; Quiroga & Lehner, 2018; Rambold et al., 2015). Due to their hydrophobic character, free fatty acids exported to the blood plasma are transported by albumin toward the muscle and liver tissues. Uptake of fatty acids into the liver or muscle cells is carried out by Fatty Acid Binding Protein (FABP), Fatty Acid Transporter Protein (FATP), and Fatty Acid Transporter (FAT-CD36) (Figure 1). Intracellular fatty acids are then activated in the form of acyl-CoA in hepatocytes and muscle cells and subsequently translocated into the mitochondrial matrix by the fatty acid transporter CAT1 and degraded by β-oxidation (Figure 1).

Acetyl-CoA overproduction by β-oxidation of fatty acids causes the allosteric inhibition of the pyruvate dehydrogenase complex (Figure 1). This allows the production of OAA from pyruvate, and thus the beginning of hepatic gluconeogenesis (Figure 1) (Fuchs et al., 2012; Sánchez-Gurmaches et al., 2018). Glycerol obtained from TAG degradation is incorporated at the level of DHAP, feeding the gluconeogenesis in the liver (Figure 1). Glycerol is the most efficient gluconeogenic substrate, compared to alanine, lactate, and other carbon skeletons of some gluconeogenic amino acids (Figure 1). In energy terms, the synthesis of one molecule of glucose from glycerol requires two ATP molecules, instead of six ATP equivalents if gluconeogenesis begins from pyruvate (Fry & Carter, 2019; Pietrocola et al., 2017).

Hepatic metabolism of fructose

Fructose, obtained from fruits and honey, is an intense-flavor sweetener that is added to most processed foods (Bray, 2013; Feinman & Fine, 2013). Fructose presentations include free fructose, sucrose, polysaccharides (fructans) in syrups and nectars, among others (Choo et al., 2018). The rise in fructose consumption has been associated with the increase in obesity and the onset of the metabolic syndrome (Elliott, Keim, Stern, Teff & Havel, 2002; Sievenpiper et al., 2014) (Figure 2). This type of sugar is metabolized largely by hepatocytes, and its assimilation takes place in parallel with the catabolism of other hexoses in glycolysis (Ter Horst & Serlie, 2017). Glut 2 mediates the transport of fructose into the hepatocytes, and the monosaccharide is phosphorylated by fructokinase C, also known as ketohexokinase. Glyceraldehyde and DHAP are produced from fructose 1-phosphate by aldolase B, which allows the integration of fructose into the middle part of glycolysis (Figure 2).

Figure 2

Metabolic pathways involved in the assimilation of fructose. Abbreviations: TAG, Triacylglycerol; DAG, Diacylglycerol; MAG, Monoacylglycerol; IMP; Inosine monophosphate; AMP; Adenosine monophosphate. Modified from Nelson & Cox, 2017.

1405-888X-tip-23-e270-gf2.png

Fructose is a highly lipogenic sugar in comparison with other monosaccharides (Loza-Medrano et al., 2019; Mai & Yan, 2019), because it enters the glycolytic pathway without any allosteric or hormonal control of the fructokinase C. For instance, hexokinases and PFK-1 prevent an accelerated rate of ATP consumption and avoid the overproduction of ADP and trioses that feed lipogenesis (Abdelmalek et al., 2012; Mock, Lateef, Benedito & Tou, 2017).

The increase in the formation of DHAP derived from fructose metabolism, augments the synthesis of fatty acids and the accumulation of triacylglycerol deposits that can progress to steatosis (Figure 2), along with an increase in VLDL and a decrease in High-Density Lipoproteins (HDL) (Ishimoto et al., 2013; Roglans et al., 2007).

At the molecular level, frequent fructose intake increases the production of mRNAs for FAS and the stearoyl-CoA desaturase 1 (SCD1), which stimulates the synthesis of triacylglycerols and the introduction of the first double bond to the saturated fatty acids, respectively (Basaranoglu, Basaranoglu, Sabuncu & Senturk, 2013). In addition, fructose increases the mRNA of the Carbohydrate-Responsive Element-Binding Proteins (ChREBP) and the mRNA of proteins that participate in the STAT3 pathway involved in the release of leptin (Roglans et al., 2007). It has been stated that ChREBP is a transcription factor that regulates the synthesis of enzymes participating in glycolysis, fructolysis and gluconeogenesis. Also, ChREBP is involved in the de novo synthesis of triacylglycerols and cholesterol, regardless of insulin activation (Ter Horst & Serlie, 2017).

Frequent fructose intake is associated with hypertension, insulin resistance, steatosis and hypertriglyceridemia, and causes non-alcoholic fatty liver disease in people with obesity, in which the nuclear receptor PPARαɣ and its target NF-κβ participate in the decrease of the rate of β- oxidation under gluconeogenesis conditions (Costa Gil & Spinedi, 2017; Laughlin et al., 2014; Roglans et al., 2002). High fructose intake is also related to the onset of gout disease (Figure 1). As a consequence of the increase in fructokinase C activity and the associated high rate of ATP consumption, there is a rise in the concentrations of ADP and AMP that causes a higher production of uric acid and inflammation of some joints (Mai & Yan, 2019). The link between fructose intake and gout arthritis has been observed in various animal models within minutes after the ingestion of fructose (Jensen et al., 2018).

In addition, the increase of uric acid levels results in the activation of cytosolic NADPH oxidase that translocates to the mitochondria, generating oxidative stress and the inhibition of the aconitase 2, and resulting in the accumulation of citrate in the mitochondrial matrix (Jamnik et al., 2016; Jensen et al., 2018). This causes the export of citrate to the cytoplasm and the stimulation of lipogenesis and cholesterogenesis (Figure 1). The oxidative stress in mitochondria spreads to the endoplasmic reticulum, activating the Sterol Regulatory Element-Binding transcription factor 1 (SREBP-1), which in turn increases the transcript levels of genes involved in lipogenesis and cholesterol synthesis (Jensen et al., 2018; Lustig, 2010; Samuel, 2011) (Figure 1).

Control of Randle cycle by mTORC1 and AMPK

The mammalian target of rapamycin (mTOR) is a kinase that forms two complexes in mammals: mTORC1 and mTORC2. mTORC1 is activated by amino acids (Chen, Wei, Liu & Guan, 2014; Cheng & Saltiel, 2006), growth factors and hormones, such as insulin (Baena et al., 2015; Verges, 2018). mTORC2 is also regulated by growth factors and is involved in cytoskeleton remodeling and sphingolipid synthesis (Figure 3). During the postprandial state, insulin stimulates phosphoinositide-dependent kinase 1 (PDK1), which leads to the activation of PKB/Akt signaling pathway, inhibition of the TSC1/TSC2 complex (tuberous sclerosis complex 1 and 2), and activation of mTORC1, which promotes lipogenesis, glycolysis, and glycogen synthesis (Asati, Mahapatra & Bharti, 2016; Jiang et al., 2008; Kumar et al., 2010; Naito, Kuma & Mizushima, 2013; Verges, 2018). On the contrary, the AMP-dependent Kinase (AMPK) is hormonally downregulated under the hyperglycemia status and activated during fasting or exercise conditions. Activation of the AMPK depends on the stimulation of both the AMPc-dependent protein kinase (PKA) and the human tumor suppressor liver kinase 1 (LKB1), and the increase in the concentration of AMP (Kim & He, 2013). Along with the stimulation of PKA and AMPK there is a decrease in the main lipogenic pathways, such as fatty acid synthesis, triacylglycerol accumulation and cholesterogenesis, and activation of gluconeogenesis (Hasenour et al., 2017), glycogen degradation, lipolysis and mitochondrial β-oxidation, thereby increasing ketogenesis in the liver (Cardaci, Filomeni, & Ciriolo, 2012). AMPK, through the phosphorylation of ACC and HMG-CoA reductase, inhibits the synthesis of fatty acids and cholesterol, respectively.

Figure 3

Functional relationships between mTORC1 and the AMP activated protein kinase (AMPK) in the Randle cycle. Abbreviations: AMPK: AMP-Activated Protein Kinase; mTORC1: mammalian Target of Rapamycin Complex 1; PIP2: phosphatidylinositol (4,5)-bisphosphate; PI3K: phosphoinositide 3 kinase; PIP3: phosphatidylinositol (3,4,5)-trisphosphate; PDK1: 3-phosphoinositide-dependent kinase-1; PKB/Akt: protein kinase B/Akt; TSC1-TSC2: 1-2 tuberous sclerosis complex (or hamartin-tuberin complex); PKA: Protein Kinase A; LKB1: Liver Kinase B1. Modified from Yoon, 2017.

1405-888X-tip-23-e270-gf3.png

In short, triacylglycerol accumulation in white fat deposits, liver tissue, and between fiber bundles is caused by hypercaloric diets rich in fast-digesting carbohydrates, along with the sedentary lifestyle habits of Western societies (Perera & Turner, 2016). Hypertriglyceridemia and hypercholesterolemia are involved in the pathophysiology of health problems, such as high blood pressure, diabetes mellitus 2, atherosclerosis and obesity, among other diseases (Ke, Xu, Li, Luo & Huang, 2018; Nakamura et al., 2014; Palomer et al., 2013; Possik et al., 2017).

Conclusions

There is a metabolic relationship between sugar consumption and fat accumulation. In the specific case of fructose, the excessive consumption of this sugar causes depletion of cellular ATP, steatosis, obesity, metabolic syndrome, and an increase in the production of uric acid. These adverse metabolic effects are the consequence of the lack of regulatory mechanisms for the incorporation of fructose into the glycolytic pathway. A new addition to the Randle cycle is the incorporation of mTORC1 and the antagonistic effect of the AMPK to ensure an efficient regulation of lipogenesis and lipolysis, respectively. In terms of public policy, authorities of health institutes should advise against the abuse of carbohydrate consumption.

Acknowledgments

This work was supported by the Universidad Nacional Autónoma de México (UNAM), Programa de Apoyo a Proyectos de Investigación Tecnológica [PAPIIT IN222117]; Consejo Nacional de Ciencia y Tecnología, CONACYT [254904-JPP] and [256520-GGS]. Instituto Politécnico Nacional- Secretaría de Investigación y Posgrado, [IPN-SIP 20190200]. We are grateful to Oscar Iván Luqueño Bocardo for the design of Figure 1.

References

1 

Abdelmalek, M. F, Lazo, M., Horska, A., Bonekamp, S., Lipkin, E. W., Balasubramanyam, A., Bantle, J. P., Johnson, R. J., Diehl, A. M. & Clark, J. M. Fatty Liver Subgroup of Look AHEAD Research Group. (2012). Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes. Hepatology, 56(3), 952-960. DOI: 10.1002/hep.25741

M. F Abdelmalek M. Lazo A. Horska S. Bonekamp E. W. Lipkin A. Balasubramanyam J. P. Bantle R. J. Johnson A. M. Diehl J. M. Clark Fatty Liver Subgroup of Look AHEAD Research Group 2012Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetesHepatology56(3)95296010.1002/hep.25741

2 

Aguilar, L. R. , Pardo, J. P., Lomelí, M. M., Bocardo, O. I. L., Juárez Oropeza, M. A. & Guerra Sánchez, G. (2017). Lipid droplets accumulation and other biochemical changes induced in the fungal pathogen Ustilago maydis under nitrogen-starvation. Arch. Microbiol., 199(8):1195-1209. DOI: 10.1007/s00203-017-1388-8

L. R. Aguilar J. P. Pardo M. M. Lomelí O. I. L. Bocardo M. A. Juárez Oropeza G. Guerra Sánchez 2017Lipid droplets accumulation and other biochemical changes induced in the fungal pathogen Ustilago maydis under nitrogen-starvationArch. Microbiol.199(8)1195120910.1007/s00203-017-1388-8

3 

Ameer, F., Scandiuzzi, L., Hasnain, S., Kalbacher, H. & Zaidi, N. (2014). De novo lipogenesis in health and disease. Metabolism, 63 (7), 895-902. DOI: 10.1016/j.metabol.2014.04.003

F. Ameer L. Scandiuzzi S. Hasnain H. Kalbacher N. Zaidi 2014De novo lipogenesis in health and diseaseMetabolism63(7)89590210.1016/j.metabol.2014.04.003

4 

Asati, V., Mahapatra, D. K. & Bharti, S. K. (2016). PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives. Eur. J. Med. Chem., 109, 314-341. DOI: 10.1016/j.ejmech.2016.01.012

V. Asati D. K. Mahapatra S. K. Bharti 2016PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectivesEur. J. Med. Chem.10931434110.1016/j.ejmech.2016.01.012

5 

Baena, M., Sanguesa, G., Hutter, N., Sánchez, R. M., Roglans, N., Laguna, J. C. & Alegret, M. (2015). Fructose supplementation impairs rat liver autophagy through mTORC activation without inducing endoplasmic reticulum stress. Biochim. Biophys. Acta, 1851(2), 107-116. DOI: 10.1016/j.bbalip.2014.11.003

M. Baena G. Sanguesa N. Hutter R. M. Sánchez N. Roglans J. C. Laguna M. Alegret 2015Fructose supplementation impairs rat liver autophagy through mTORC activation without inducing endoplasmic reticulum stressBiochim. Biophys. Acta1851(2)10711610.1016/j.bbalip.2014.11.003

6 

Barbosa, A. D. & Siniossoglou, S. (2017). Function of lipid droplet-organelle interactions in lipid homeostasis. Biochim. Biophys. Acta Mol. Cell Res., 1864(9), 1459-1468. DOI: 10.1016/j.bbamcr.2017.04.001

A. D. Barbosa S. Siniossoglou 2017Function of lipid droplet-organelle interactions in lipid homeostasisBiochim. Biophys. Acta Mol. Cell Res.1864(9)1459146810.1016/j.bbamcr.2017.04.001

7 

Bartelt, A., Weigelt, C., Cherradi, M. L., Niemeier, A., Todter, K., Heeren, J. & Scheja, L. (2013). Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browning. Biochim Biophys Acta, 1831(5), 934-942. DOI: 10.1016/j.bbalip.2012.11.011

A. Bartelt C. Weigelt M. L. Cherradi A. Niemeier K. Todter J. Heeren L. Scheja 2013Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browningBiochim Biophys Acta1831(5)93494210.1016/j.bbalip.2012.11.011

8 

Basaranoglu, M., Basaranoglu, G., Sabuncu, T. & Senturk, H. (2013). Fructose as a key player in the development of fatty liver disease. World J. Gastroenterol., 19(8), 1166-1172. DOI: 10.3748/wjg.v19.i8.1166

M. Basaranoglu G. Basaranoglu T. Sabuncu H. Senturk 2013Fructose as a key player in the development of fatty liver diseaseWorld J. Gastroenterol.19(8)1166117210.3748/wjg.v19.i8.1166

9 

Bray, G. A. (2013). Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some people. Adv. Nutr., 4(2), 220-225. DOI: 10.3945/an.112.002816

G. A. Bray 2013Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some peopleAdv. Nutr.4(2)22022510.3945/an.112.002816

10 

Cardaci, S., Filomeni, G. & Ciriolo, M. R. (2012). Redox implications of AMPK-mediated signal transduction beyond energetic clues. J. Cell Sci., 125(Pt 9), 2115-2125. DOI: 10.1242/jcs.095216

S. Cardaci G. Filomeni M. R. Ciriolo 2012Redox implications of AMPK-mediated signal transduction beyond energetic cluesJ. Cell Sci.125(Pt9)2115212510.1242/jcs.095216

11 

Chen, Y., Wei, H., Liu, F. & Guan, J. L. (2014). Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) promotes breast cancer progression through enhancing glucose starvation-induced autophagy and Akt signaling. J. Biol. Chem., 289(2), 1164-1173. DOI: 10.1074/jbc.M113.526335

Y. Chen H. Wei F. Liu J. L. Guan 2014Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) promotes breast cancer progression through enhancing glucose starvation-induced autophagy and Akt signalingJ. Biol. Chem.289(2)1164117310.1074/jbc.M113.526335

12 

Cheng, A. & Saltiel, A. R. (2006). More TORC for the gluconeogenic engine. Bioessays, 28(3), 231-234. DOI: 10.1002/bies.20375

A. Cheng A. R. Saltiel 2006More TORC for the gluconeogenic engineBioessays28(3)23123410.1002/bies.20375

13 

Choo, V. L., Viguiliouk, E., Blanco Mejia, S., Cozma, A. I., Khan, T.A., Ha, V., Wolever, T. M. S., Leiter, L. A., Vuksan, V., Kendall, C. W. C., de Souza, R. J., Jenkins, D. J. A. & Sievenpiper, J. L. (2018). Food sources of fructose-containing sugars and glycaemic control: systematic review and meta-analysis of controlled intervention studies. BMJ, 363, k4644. DOI: 10.1136/bmj.k4644

V. L. Choo E. Viguiliouk S. Blanco Mejia A. I. Cozma T.A. Khan V. Ha T. M. S. Wolever L. A. Leiter V. Vuksan C. W. C. Kendall R. J. de Souza D. J. A. Jenkins J. L. Sievenpiper 2018Food sources of fructose-containing sugars and glycaemic control: systematic review and meta-analysis of controlled intervention studiesBMJ363k4644k464410.1136/bmj.k4644

14 

Costa Gil, J. E. & Spinedi, E. (2017). La tormentosa relación entre las grasas y el desarrollo de la diabetes mellitus de tipo 2: actualizado. Parte I. Revista Argentina de Endocrinología y Metabolismo, 54, 109-123. DOI: 10.1016/j.raem.2017.06.001

J. E. Costa Gil E. Spinedi 2017La tormentosa relación entre las grasas y el desarrollo de la diabetes mellitus de tipo 2: actualizadoParte IRevista Argentina de Endocrinología y Metabolismo5410912310.1016/j.raem.2017.06.001

15 

Elliott, S. S., Keim, N. L., Stern, J. S., Teff, K. & Havel, P. J. (2002). Fructose, weight gain, and the insulin resistance syndrome. Am. J. Clin. Nutr., 76(5), 911-922. DOI: 10.1093/ajcn/76.5.911

S. S. Elliott N. L. Keim J. S. Stern K. Teff P. J. Havel 2002Fructose, weight gain, and the insulin resistance syndromeAm. J. Clin. Nutr.76(5)91192210.1093/ajcn/76.5.911

16 

Feinman, R. D. & Fine, E. J. (2013). Fructose in perspective. Nutr. Metab. (Lond.), 10(1), 45. DOI: 10.1186/1743-7075-10-45

R. D. Feinman E. J. Fine 2013Fructose in perspectiveNutr. Metab. (Lond.)10(1)454510.1186/1743-7075-10-45

17 

Fry, B. & Carter, J. F. (2019). Stable carbon isotope diagnostics of mammalian metabolism, a high-resolution isotomics approach using amino acid carboxyl groups. PLoS One, 14(10), e0224297. DOI: 10.1371/journal.pone.0224297

B. Fry J. F. Carter 2019Stable carbon isotope diagnostics of mammalian metabolism, a high-resolution isotomics approach using amino acid carboxyl groupsPLoS One14(10)e022429710.1371/journal.pone.0224297

18 

Fuchs, C. D., Claudel, T., Kumari, P., Haemmerle, G., Pollheimer, M. J., Stojakovic, T., Scharnagl, H., Halilbasic, E., Gumhold, J., Silbert, D., Koefeler, H. & Trauner, M. (2012). Absence of adipose triglyceride lipase protects from hepatic endoplasmic reticulum stress in mice. Hepatology, 56(1), 270-280. DOI: 10.1002/hep.25601

C. D. Fuchs T. Claudel P. Kumari G. Haemmerle M. J. Pollheimer T. Stojakovic H. Scharnagl E. Halilbasic J. Gumhold D. Silbert H. Koefeler M. Trauner 2012Absence of adipose triglyceride lipase protects from hepatic endoplasmic reticulum stress in miceHepatology56(1)27028010.1002/hep.25601

19 

Gómez Candela, C. & Palma Milla, S. (2013). Una visión global, actualizada y crítica del papel del azúcar en nuestra alimentación. Nutrición Hospitalaria, 28, 1-4.

C. Gómez Candela S. Palma Milla 2013Una visión global, actualizada y crítica del papel del azúcar en nuestra alimentaciónNutrición Hospitalaria2814

20 

Hasenour, C. M., Ridley, D. E., James, F. D., Hughey, C. C., Donahue, E. P., Viollet, B., Foretz, M., Young, J. D. & Wasserman, D. H. (2017). Liver AMP-Activated Protein Kinase Is Unnecessary for Gluconeogenesis but Protects Energy State during Nutrient Deprivation. PLoS One, 12(1), e0170382. DOI: 10.1371/journal.pone.0170382

C. M. Hasenour D. E. Ridley F. D. James C. C. Hughey E. P. Donahue B. Viollet M. Foretz J. D. Young D. H. Wasserman 2017Liver AMP-Activated Protein Kinase Is Unnecessary for Gluconeogenesis but Protects Energy State during Nutrient DeprivationPLoS One12(1)e017038210.1371/journal.pone.0170382

21 

Hilton, C., Karpe, F. & Pinnick, K. E. (2015). Role of developmental transcription factors in white, brown and beige adipose tissues. Biochim. Biophys. Acta, 1851(5), 686-696. DOI: 10.1016/j.bbalip.2015.02.003

C. Hilton F. Karpe K. E. Pinnick 2015Role of developmental transcription factors in white, brown and beige adipose tissuesBiochim. Biophys. Acta1851(5)68669610.1016/j.bbalip.2015.02.003

22 

Hruby, A. & Hu, F. B. (2015). The Epidemiology of Obesity: A Big Picture. Pharmacoeconomics, 33(7), 673-689. DOI: 10.1007/s40273-014-0243-x

A. Hruby F. B. Hu 2015The Epidemiology of Obesity: A Big PicturePharmacoeconomics33(7)67368910.1007/s40273-014-0243-x

23 

Ishimoto, T., Lanaspa, M. A., Rivard, C. J., Roncal-Jimenez, C. A., Orlicky, D. J., Cicerchi, C., McMahan, R. H., Abdelmalek, M. F., Rosen, H. R., Jackman, M. R., MacLean, P. S., Diggle, C. P., Asipu, A., Inaba, S., Kosugi, T., Sato, W., Maruyama, S., Sánchez-Lozada, L. G., Sautin, Y.Y ., Hill, J. O., Bonthron, D. T. & Johnson, R. J. (2013). High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase. Hepatology, 58(5), 1632-1643. DOI: 10.1002/hep.26594

T. Ishimoto M. A. Lanaspa C. J. Rivard C. A. Roncal-Jimenez D. J. Orlicky C. Cicerchi R. H. McMahan M. F. Abdelmalek H. R. Rosen M. R. Jackman P. S. MacLean C. P. Diggle A. Asipu S. Inaba T. Kosugi W. Sato S. Maruyama L. G. Sánchez-Lozada Y.Y . Sautin J. O. Hill D. T. Bonthron R. J. Johnson 2013High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinaseHepatology58(5)1632164310.1002/hep.26594

24 

Jamnik, J., Rehman, S., Blanco Mejia, S., de Souza, R. J, Khan, T. A., Leiter, L. A., Wolever, T. M., Kendall, C. W., Jenkins, D. J. & Sievenpiper, J. L. (2016). Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studies. BMJ Open, 6(10), e013191. DOI: 10.1136/bmjopen-2016-013191

J. Jamnik S. Rehman S. Blanco Mejia R. J de Souza T. A. Khan L. A. Leiter T. M. Wolever C. W. Kendall D. J. Jenkins J. L. Sievenpiper 2016Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studiesBMJ Open6(10)e01319110.1136/bmjopen-2016-013191

25 

Jensen, T., Abdelmalek, M. F., Sullivan, S., Nadeau, K. J., Green, M., Roncal, C., Nakagawa, T., Kuwabara, M., Sato, Y., Kang, D. H., Tolan, D. R., Sanchez-Lozada, L. G., Rosen, H. R, Lanaspa, M. A., Diehl, A. M. & Johnson, R. J. (2018). Fructose and sugar: A major mediator of non-alcoholic fatty liver disease. J. Hepatol., 68(5), 1063-1075. DOI: 10.1016/j.jhep.2018.01.019

T. Jensen M. F. Abdelmalek S. Sullivan K. J. Nadeau M. Green C. Roncal T. Nakagawa M. Kuwabara Y. Sato D. H. Kang D. R. Tolan L. G. Sanchez-Lozada H. R Rosen M. A. Lanaspa A. M. Diehl R. J. Johnson 2018Fructose and sugar: A major mediator of non-alcoholic fatty liver diseaseJ. Hepatol.68(5)1063107510.1016/j.jhep.2018.01.019

26 

Jiang, X., Kenerson, H., Aicher, L., Miyaoka, R., Eary, J., Bissler, J. & Yeung, R. S. (2008). The tuberous sclerosis complex regulates trafficking of glucose transporters and glucose uptake. Am. J. Pathol., 172(6), 1748-1756. DOI: 10.2353/ajpath.2008.070958

X. Jiang H. Kenerson L. Aicher R. Miyaoka J. Eary J. Bissler R. S. Yeung 2008The tuberous sclerosis complex regulates trafficking of glucose transporters and glucose uptakeAm. J. Pathol.172(6)1748175610.2353/ajpath.2008.070958

27 

Ke, R., Xu, Q., Li, C., Luo, L. & Huang, D. (2018). Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism. Cell Biol. In.. 42(4), 384-392. DOI: 10.1002/cbin.10915

R. Ke Q. Xu C. Li L. Luo D. Huang 2018Mechanisms of AMPK in the maintenance of ATP balance during energy metabolismCell Biol. In.42(4)38439210.1002/cbin.10915

28 

Kim, I. & He, Y. Y. (2013). Targeting the AMP-Activated Protein Kinase for Cancer Prevention and Therapy. Front. Oncol., 3, 175. DOI: 10.3389/fonc.2013.00175

I. Kim Y. Y. He 2013Targeting the AMP-Activated Protein Kinase for Cancer Prevention and TherapyFront. Oncol.317517510.3389/fonc.2013.00175

29 

Kory, N., Farese, R. V., Jr. & Walther, T. C. (2016). Targeting Fat: Mechanisms of Protein Localization to Lipid Droplets. Trends Cell Biol., 26(7), 535-546. DOI: 10.1016/j.tcb.2016.02.007

N. Kory R. V. Farese Jr T. C. Walther 2016Targeting Fat: Mechanisms of Protein Localization to Lipid DropletsTrends Cell Biol.26(7)53554610.1016/j.tcb.2016.02.007

30 

Kumar, A., Lawrence, J. C. Jr. , Jung, D.Y., Ko, H. J., Keller, S. R., Kim, J. K., Magnuson, M. A. & Harris, T. E. (2010). Fat cell-specific ablation of rictor in mice impairs insulin-regulated fat cell and whole-body glucose and lipid metabolism. Diabetes, 59(6), 1397-1406. DOI: 10.2337/db09-1061

A. Kumar J. C. Lawrence Jr. D.Y. Jung H. J. Ko S. R. Keller J. K. Kim M. A. Magnuson T. E. Harris 2010Fat cell-specific ablation of rictor in mice impairs insulin-regulated fat cell and whole-body glucose and lipid metabolismDiabetes59(6)1397140610.2337/db09-1061

31 

Laughlin, M. R., Bantle, J. P., Havel, P. J., Parks, E., Klurfeld, D. M., Teff, K. & Maruvada, P. (2014). Clinical research strategies for fructose metabolism. Adv. Nutr., 5(3), 248-259. DOI: 10.3945/an.113.005249

M. R. Laughlin J. P. Bantle P. J. Havel E. Parks D. M. Klurfeld K. Teff P. Maruvada 2014Clinical research strategies for fructose metabolismAdv. Nutr.5(3)24825910.3945/an.113.005249

32 

Loza-Medrano, S. S., Baiza-Gutman, L. A., Manuel-Apolinar, L., García-Macedo, R., Damasio-Santana, L., Martínez-Mar, O. A., Sánchez-Becerra, M. C., Cruz-López, M., Ibáñez-Hernández, M. A. & Díaz-Flores, M. (2019). High fructose-containing drinking water-induced steatohepatitis in rats is prevented by the nicotinamide-mediated modulation of redox homeostasis and NADPH-producing enzymes. Mol. Biol. Rep., 47(1), 337-351. DOI: 10.1007/s11033-019-05136-4

S. S. Loza-Medrano L. A. Baiza-Gutman L. Manuel-Apolinar R. García-Macedo L. Damasio-Santana O. A. Martínez-Mar M. C. Sánchez-Becerra M. Cruz-López M. A. Ibáñez-Hernández M. Díaz-Flores 2019High fructose-containing drinking water-induced steatohepatitis in rats is prevented by the nicotinamide-mediated modulation of redox homeostasis and NADPH-producing enzymesMol. Biol. Rep.47(1)33735110.1007/s11033-019-05136-4

33 

Lustig, R. H. (2010). Fructose: metabolic, hedonic, and societal parallels with ethanol. J. Am. Diet. Assoc., 110(9), 1307-1321. DOI: 10.1016/j.jada.2010.06.008

R. H. Lustig 2010Fructose: metabolic, hedonic, and societal parallels with ethanolJ. Am. Diet. Assoc.110(9)1307132110.1016/j.jada.2010.06.008

34 

Mai, B. H. & Yan, L. J. (2019). The negative and detrimental effects of high fructose on the liver, with special reference to metabolic disorders. Diabetes Metab. Syndr. Obes., 12, 821-826. DOI: 10.2147/DMSO.S198968

B. H. Mai L. J. Yan 2019The negative and detrimental effects of high fructose on the liver, with special reference to metabolic disordersDiabetes Metab. Syndr. Obes.1282182610.2147/DMSO.S198968

35 

Marcelino, H., Veyrat-Durebex, C., Summermatter, S., Sarafian, D., Miles-Chan, J., Arsenijevic, D., Zani, F., Montani, J. P., Seydoux, J., Solinas, G., Rohner-Jeanrenaud, F. & Dulloo, A. G. (2013). A role for adipose tissue de novo lipogenesis in glucose homeostasis during catch-up growth: a Randle cycle favoring fat storage. Diabetes, 62(2), 362-372. DOI: 10.2337/db12-0255

H. Marcelino C. Veyrat-Durebex S. Summermatter D. Sarafian J. Miles-Chan D. Arsenijevic F. Zani J. P. Montani J. Seydoux G. Solinas F. Rohner-Jeanrenaud A. G. Dulloo 2013A role for adipose tissue de novo lipogenesis in glucose homeostasis during catch-up growth: a Randle cycle favoring fat storageDiabetes62(2)36237210.2337/db12-0255

36 

Mock, K., Lateef, S., Benedito, V. A. & Tou, J. C. (2017). High-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulation. J. Nutr. Biochem., 39, 32-39. DOI: 10.1016/j.jnutbio.2016.09.010

K. Mock S. Lateef V. A. Benedito J. C. Tou 2017High-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulationJ. Nutr. Biochem.39,323910.1016/j.jnutbio.2016.09.010

37 

Moran, T. H. & Ladenheim, E. E. (2016). Physiologic and Neural Controls of Eating. Gastroenterol. Clin. North. Am., 45(4), 581-599. DOI: 10.1016/j.gtc.2016.07.009

T. H. Moran E. E. Ladenheim 2016Physiologic and Neural Controls of EatingGastroenterol. Clin. North. Am.45(4)58159910.1016/j.gtc.2016.07.009

38 

Mottillo, E. P., Balasubramanian, P., Lee, Y. H., Weng, C., Kershaw, E. E. & Granneman, J. G. (2014). Coupling of lipolysis and de novo lipogenesis in brown, beige, and white adipose tissues during chronic beta3-adrenergic receptor activation. J. Lipid. Res., 55(11), 2276-2286. DOI: 10.1194/jlr.M050005

E. P. Mottillo P. Balasubramanian Y. H. Lee C. Weng E. E. Kershaw J. G. Granneman 2014Coupling of lipolysis and de novo lipogenesis in brown, beige, and white adipose tissues during chronic beta3-adrenergic receptor activationJ. Lipid. Res.55(11)2276228610.1194/jlr.M050005

39 

Murray, R. D. (2019). 100% Fruit Juice in Child and Adolescent Dietary Patterns. J. Am. Coll. Nutr., 39(2), 122-127. DOI: 10.1080/07315724.2019.1615013

R. D. Murray 2019100% Fruit Juice in Child and Adolescent Dietary PatternsJ. Am. Coll. Nutr.39(2)12212710.1080/07315724.2019.1615013

40 

Naito, T., Kuma, A. & Mizushima, N. (2013). Differential contribution of insulin and amino acids to the mTORC1-autophagy pathway in the liver and muscle. J. Biol. Chem., 288(29), 21074-21081. DOI: 10.1074/jbc.M113.456228

T. Naito A. Kuma N. Mizushima 2013Differential contribution of insulin and amino acids to the mTORC1-autophagy pathway in the liver and muscleJ. Biol. Chem.288(29)210742108110.1074/jbc.M113.456228

41 

Nakamura, M. T., Yudell, B. E. & Loor, J. J. (2014). Regulation of energy metabolism by long-chain fatty acids. Prog. Lipid. Res., 53, 124-144. DOI: 10.1016/j.plipres.2013.12.001

M. T. Nakamura B. E. Yudell J. J. Loor 2014Regulation of energy metabolism by long-chain fatty acidsProg. Lipid. Res.53,12414410.1016/j.plipres.2013.12.001

42 

Nelson, D. L. & Cox, M. (2017). Lehninger principles of biochemistry. W.H. Freeman. New York.

D. L. Nelson M. Cox 2017Lehninger principles of biochemistryW.H. FreemanNew York

43 

Ogden, C. L., Yanovski, S. Z., Carroll, M. D. & Flegal, K. M. (2007). The epidemiology of obesity. Gastroenterology, 132(6), 2087-2102. DOI: 10.1053/j.gastro.2007.03.052

C. L. Ogden S. Z. Yanovski M. D. Carroll K. M. Flegal 2007The epidemiology of obesityGastroenterology132(6)2087210210.1053/j.gastro.2007.03.052

44 

Palomer, X., Salvado, L., Barroso, E. & Vazquez-Carrera, M. (2013). An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy. Int. J. Cardiol., 168(4), 3160-3172. DOI: 10.1016/j.ijcard.2013.07.150

X. Palomer L. Salvado E. Barroso M. Vazquez-Carrera 2013An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathyInt. J. Cardiol.168(4)3160317210.1016/j.ijcard.2013.07.150

45 

Pearlman, M., Obert, J. & Casey, L. (2017). The Association Between Artificial Sweeteners and Obesity. Curr. Gastroenterol. Rep., 19(12), 64. DOI: 10.1007/s11894-017-0602-9

M. Pearlman J. Obert L. Casey 2017The Association Between Artificial Sweeteners and ObesityCurr. Gastroenterol. Rep.19(12)646410.1007/s11894-017-0602-9

46 

Pereira, M. J., Thombare, K., Sarsenbayeva, A., Kamble, P. G., Almby, K., Lundqvist, M. & Eriksson, J. W. (2020). Direct effects of glucagon on glucose uptake and lipolysis in human adipocytes. Mol. Cell Endocrinol., 503, 110696. DOI: 10.1016/j.mce.2019.110696

M. J. Pereira K. Thombare A. Sarsenbayeva P. G. Kamble K. Almby M. Lundqvist J. W. Eriksson 2020Direct effects of glucagon on glucose uptake and lipolysis in human adipocytesMol. Cell Endocrinol.50311069610.1016/j.mce.2019.110696

47 

Perera, N. D. & Turner, B. J. (2016). AMPK Signalling and Defective Energy Metabolism in Amyotrophic Lateral Sclerosis. Neurochemical Research, 41(3), 544-553. DOI: 10.1007/s11064-015-1665-3

N. D. Perera B. J. Turner 2016AMPK Signalling and Defective Energy Metabolism in Amyotrophic Lateral SclerosisNeurochemical Research41(3)54455310.1007/s11064-015-1665-3

48 

Pietrocola, F., Demont, Y., Castoldi, F., Enot, D., Durand, S., Semeraro, M., Baracco, E. E., Pol, J., Bravo-San Pedro, J. M., Bordenave, C., Levesque, S., Humeau, J., Chery, A., Métivier, D., Madeo, F., Maiuri, M. C. & Kroemer, G. (2017). Metabolic effects of fasting on human and mouse blood in vivo. Autophagy, 13(3), 567-578. DOI: 10.1080/15548627.2016.1271513

F. Pietrocola Y. Demont F. Castoldi D. Enot S. Durand M. Semeraro E. E. Baracco J. Pol J. M. Bravo-San Pedro C. Bordenave S. Levesque J. Humeau A. Chery D. Métivier F. Madeo M. C. Maiuri G. Kroemer 2017Metabolic effects of fasting on human and mouse blood in vivoAutophagy,13(3)56757810.1080/15548627.2016.1271513

49 

Possik, E., Madiraju, S. R. M. & Prentki, M. (2017). Glycerol-3-phosphate phosphatase/PGP: Role in intermediary metabolism and target for cardiometabolic diseases. Biochimie, 143, 18-28. DOI: 10.1016/j.biochi.2017.08.001

E. Possik S. R. M. Madiraju M. Prentki 2017Glycerol-3-phosphate phosphatase/PGP: Role in intermediary metabolism and target for cardiometabolic diseasesBiochimie143182810.1016/j.biochi.2017.08.001

50 

Priyadarshini, E. & Anuradha, C. V. (2017). Glucocorticoid Antagonism Reduces Insulin Resistance and Associated Lipid Abnormalities in High-Fructose-Fed Mice. Can. J. Diabetes, 41(1), 41-51. DOI: 10.1016/j.jcjd.2016.06.003

E. Priyadarshini C. V. Anuradha 2017Glucocorticoid Antagonism Reduces Insulin Resistance and Associated Lipid Abnormalities in High-Fructose-Fed MiceCan. J. Diabetes41(1)415110.1016/j.jcjd.2016.06.003

51 

Quiroga, A. D. & Lehner, R. (2012). Liver triacylglycerol lipases. Biochim. Biophys. Acta, 1821(5), 762-769. DOI:10.1016/j.bbalip.2011.09.007

A. D. Quiroga R. Lehner 2012Liver triacylglycerol lipasesBiochim. Biophys. Acta1821(5)76276910.1016/j.bbalip.2011.09.007

52 

Quiroga, A. D. & Lehner, R. (2018). Pharmacological intervention of liver triacylglycerol lipolysis: The good, the bad and the ugly. Biochem. Pharmacol., 155, 233-241. DOI: 10.1016/j.bcp.2018.07.005

A. D. Quiroga R. Lehner 2018Pharmacological intervention of liver triacylglycerol lipolysis: The good, the bad and the uglyBiochem. Pharmacol.15523324110.1016/j.bcp.2018.07.005

53 

Rambold, A. S., Cohen, S. & Lippincott-Schwartz, J. (2015). Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev. Cell, 32(6), 678-692. DOI: 10.1016/j.devcel.2015.01.029

A. S. Rambold S. Cohen J. Lippincott-Schwartz 2015Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamicsDev. Cell32(6)67869210.1016/j.devcel.2015.01.029

54 

Randle, P. J., Garland, P. B., Hales, C. N. & Newsholme, E. A. (1963). The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet, 1(7285), 785-789. DOI: 10.1016/s0140-6736(63)91500-9

P. J. Randle P. B. Garland C. N. Hales E. A. Newsholme 1963The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitusLancet1(7285)78578910.1016/s0140-6736(63)91500-9

55 

Rodríguez Delgado, J. (2017). Azúcares... ¿los malos de la dieta? Pediatría Atención Primaria, 19, 69-75.

J. Rodríguez Delgado 2017Azúcares... ¿los malos de la dieta?Pediatría Atención Primaria196975

56 

Roglans, N., Sanguino, E., Peris, C., Alegret, M., Vázquez, M., Adzet, T., Díaz, C., Hernández, G., Laguna, J. C. & Sánchez, R. M. (2002). Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats. J. Pharmacol. Exp. Ther., 302(1), 232-239. DOI: 10.1124/jpet.302.1.232

N. Roglans E. Sanguino C. Peris M. Alegret M. Vázquez T. Adzet C. Díaz G. Hernández J. C. Laguna R. M. Sánchez 2002Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed ratsJ. Pharmacol. Exp. Ther.302(1)23223910.1124/jpet.302.1.232

57 

Roglans, N., Vila, L., Farre, M., Alegret, M., Sánchez, R. M., Vázquez-Carrera, M. & Laguna, J. C. (2007). Impairment of hepatic Stat-3 activation and reduction of PPARalpha activity in fructose-fed rats. Hepatology, 45(3), 778-788. DOI: 10.1002/hep.21499

N. Roglans L. Vila M. Farre M. Alegret R. M. Sánchez M. Vázquez-Carrera J. C. Laguna 2007Impairment of hepatic Stat-3 activation and reduction of PPARalpha activity in fructose-fed ratsHepatology45(3)77878810.1002/hep.21499

58 

Samuel, V. T. (2011). Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol. Metab., 22(2), 60-65. DOI: 10.1016/j.tem.2010.10.003

V. T. Samuel 2011Fructose induced lipogenesis: from sugar to fat to insulin resistanceTrends Endocrinol. Metab.22(2)606510.1016/j.tem.2010.10.003

59 

Sánchez-Gurmaches, J., Tang, Y., Jespersen, N. Z., Wallace, M., Martinez Calejman, C., Gujja, S., Li, H., Edwards, Y. J. K., Wolfrum, C., Metallo, C. M., Nielsen, S., Scheele, C. & Guertin, D. A. (2018). Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis. Cell Metab., 27(1), 195-209 e196. DOI: 10.1016/j.cmet.2017.10.008

J. Sánchez-Gurmaches Y. Tang N. Z. Jespersen M. Wallace C. Martinez Calejman S. Gujja H. Li Y. J. K. Edwards C. Wolfrum C. M. Metallo S. Nielsen C. Scheele D. A. Guertin 2018Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and ThermogenesisCell Metab.27(1)195209e19610.1016/j.cmet.2017.10.008

60 

Sievenpiper, J. L., de Souza, R. J., Cozma, A. I., Chiavaroli, L., Ha, V. & Mirrahimi, A. (2014). Fructose vs. glucose and metabolism: do the metabolic differences matter? Curr. Opin. Lipidol., 25(1), 8-19. DOI: 10.1097/MOL.0000000000000042

J. L. Sievenpiper R. J. de Souza A. I. Cozma L. Chiavaroli V. Ha A. Mirrahimi 2014Fructose vs. glucose and metabolism: do the metabolic differences matter?Curr. Opin. Lipidol.25(1)81910.1097/MOL.0000000000000042

61 

Smith, K. B. & Smith, M. S. (2016). Obesity Statistics. Primare, 43(1), 121-135, ix. DOI: 10.1016/j.pop.2015.10.001

K. B. Smith M. S. Smith 2016Obesity StatisticsPrimare43(1)121135ix10.1016/j.pop.2015.10.001

62 

Song, Z., Xiaoli, A. M. & Yang, F. (2018). Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues. Nutrients, 10(10). DOI: 10.3390/nu10101383

Z. Song A. M. Xiaoli F. Yang 2018Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose TissuesNutrients10(10)10.3390/nu10101383

63 

Stanhope, K. L. (2016). Sugar consumption, metabolic disease and obesity: The state of the controversy. Crit. Rev. Clin. Lab. Sci., 53(1), 52-67. DOI: 10.3109/10408363.2015.1084990

K. L. Stanhope 2016Sugar consumption, metabolic disease and obesity: The state of the controversyCrit. Rev. Clin. Lab. Sci.53(1)526710.3109/10408363.2015.1084990

64 

Summermatter, S., Marcelino, H., Arsenijevic, D., Buchala, A., Aprikian, O., Assimacopoulos-Jeannet, F., Seydoux, J., Montani, J. P., Solinas, G. & Dulloo, A. G. (2009). Adipose Tissue Plasticity During Catch-Up Fat Driven by Thrifty Metabolism Diabetes, 58(10), 2228-2237. DOI: 10.2337/db08-1793

S. Summermatter H. Marcelino D. Arsenijevic A. Buchala O. Aprikian F. Assimacopoulos-Jeannet J. Seydoux J. P. Montani G. Solinas A. G. Dulloo 2009Adipose Tissue Plasticity During Catch-Up Fat Driven by Thrifty MetabolismDiabetes58(10)2228223710.2337/db08-1793

65 

Ter Horst, K. W. & Serlie, M. J. (2017). Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease. Nutrients, 9(9). DOI: 10.3390/nu9090981

K. W. Ter Horst M. J. Serlie 2017Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver DiseaseNutrients9(9)10.3390/nu9090981

66 

Verges, B. (2018). mTOR and Cardiovascular Diseases: Diabetes Mellitus. Transplantation, 102(2S Suppl 1), S47-S49. DOI: 10.1097/TP.0000000000001722

B. Verges 2018mTOR and Cardiovascular Diseases: Diabetes MellitusTransplantation102(2SSuppl1)S47S4910.1097/TP.0000000000001722

67 

Yoon, M-S. (2017). The Role of Mammalian Target of Rapamycin (mTOR) in Insulin Signaling. Nutrients 2017, 9, 1176. DOI:10.3390/nu9111176

M-S. Yoon 2017The Role of Mammalian Target of Rapamycin (mTOR) in Insulin SignalingNutrients201791176117610.3390/nu9111176

68 

World Health Organization. World Health Statistics (2018): Monitoring Health for the SDGs., 2018.

World Health Organization World Health Statistics (2018): Monitoring Health for the SDGs2018



This display is generated from NISO JATS XML with jats-html.xsl. The XSLT engine is libxslt.

Enlaces refback

  • No hay ningún enlace refback.


Financiado por:

 

Proyecto C-297282

Licencia Creative Commons
TIP Revista Especializada en Ciencias Químico-Biológicas está distribuido bajo una Licencia Creative Commons Atribución-NoComercial-SinDerivar 4.0 Internacional.

TIP REVISTA ESPECIALIZADA EN CIENCIAS QUÍMICO-BIOLÓGICAS, Volumen 24, 2021, es una publicación editada por la Universidad Nacional Autónoma de México, Ciudad Universitaria, Deleg. Coyoacán, C.P. 04510, Ciudad de México, México, a través de la Facultad de Estudios Superiores Zaragoza, Campus I, Av. Guelatao # 66, Col. Ejército de Oriente, Deleg. Iztapalapa, C.P. 09230, Ciudad de México, México, Teléfono: 55.56.23.05.27, http://tip.zaragoza.unam.mx, Correo electrónico revistatip@yahoo.com, Editor responsable: Dra. Martha Asunción Sánchez Rodríguez, Certificado de Reserva de Derechos al Uso Exclusivo del Título No. 04-2014-062612263300-203, ISSN impreso: 1405-888X, ISSN electrónico: 2395-8723, otorgados por el Instituto Nacional del Derecho de Autor, Responsable de la última actualización de este número Claudia Ahumada Ballesteros, Facultad de Estudios Superiores Zaragoza, Av. Guelatao # 66, Col. Ejército de Oriente, Deleg. Iztapalapa, C.P. 09230, Ciudad de México, México, fecha de la última modificación, 4 de febrero de 2021.

Esta página puede ser reproducida con fines no lucrativos, siempre y cuando no se mutile, se cite la fuente completa y su dirección electrónica. De otra forma requiere permiso previo de la institución.