Liver AMP/ATP ratio and fructokinase expression are related to gender differences in AMPK activity and glucose intolerance in rats ingesting liquid fructose

Vilà, Laia; Roglans, Núria; Perna, Victoria; Sánchez, Rosa María Galán; Vázquez‐Carrera, Manuel; Alegret, Marta; Laguna, Juan C.

doi:10.1016/j.jnutbio.2010.06.005

Cited by 87 publications

(79 citation statements)

References 44 publications

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“…It is interesting to note that fructose modulation of AMPK may be confounded by gender. The expression of KHK and the activity of G-6-Pase were significantly enhanced via AMPK phosphorylation in the liver of female adult rats (52) and in the female offspring from fructose-fed dams (37). However, AMPK has also been shown to repress hepatic gluconeogenesis (31).…”

Section: R505 Fructose Regulates Fructolytic and Gluconeogenic Genesmentioning

confidence: 99%

“…Intestinal AMPK activation by 5-aminoimidazole-4-carboxamide ribonucleotide increases GLUT5 expression in the small intestine of perfused rats (Patel and Ferraris, unpublished observations). Moreover, fructose-induced activation of hepatic AMPK requires KHK (52). It is interesting to note that fructose modulation of AMPK may be confounded by gender.…”

Section: R505 Fructose Regulates Fructolytic and Gluconeogenic Genesmentioning

confidence: 99%

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Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK

Patel

Douard

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Patel C, Douard V, Yu S, Tharabenjasin P, Gao N, Ferraris RP. Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK. Am J Physiol Regul Integr Comp Physiol 309: R499 -R509, 2015. First published June 17, 2015; doi:10.1152/ajpregu.00128.2015.-Marked increases in fructose consumption have been tightly linked to metabolic diseases. One-third of ingested fructose is metabolized in the small intestine, but the underlying mechanisms regulating expression of fructose-metabolizing enzymes are not known. We used genetic mouse models to test the hypothesis that fructose absorption via glucose transporter protein, member 5 (GLUT5), metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein in brain 11a (Rab11a)-dependent endosomes are required for the regulation of intestinal fructolytic and gluconeogenic enzymes. Fructose feeding increased the intestinal mRNA and protein expression of these enzymes in the small intestine of adult wild-type (WT) mice compared with those gavage fed with lysine or glucose. Fructose did not increase expression of these enzymes in the GLUT5 knockout (KO) mice. Blocking intracellular fructose metabolism by KHK ablation also prevented fructose-induced upregulation. Glycolytic hexokinase I expression was similar between WT and GLUT5-or KHK-KO mice and did not vary with feeding solution. Gavage feeding with the fructose-specific metabolite glyceraldehyde did not increase enzyme expression, suggesting that signaling occurs before the hydrolysis of fructose to three-carbon compounds. Impeding GLUT5 trafficking to the apical membrane using intestinal epithelial cell-specific Rab11a-KO mice impaired fructose-induced upregulation. KHK expression was uniformly distributed along the villus but was localized mainly in the basal region of the cytosol of enterocytes. The feedforward upregulation of fructolytic and gluconeogenic enzymes specifically requires GLUT5 and KHK and may proactively enhance the intestine's ability to process anticipated increases in dietary fructose concentrations. fructolysis; glyceraldehyde; gluconeogenesis; glucose transporter protein, member 5; ketohexokinase; Ras-related protein in brain 11a; mice; small intestine

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Section: R505 Fructose Regulates Fructolytic and Gluconeogenic Genesmentioning

confidence: 99%

Section: R505 Fructose Regulates Fructolytic and Gluconeogenic Genesmentioning

confidence: 99%

Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK

Patel

Douard

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…We have modified the sentence, and added some discussion on fructose effects at 7 days (pg 16, ln [18][19][20] of the new version of the manuscript).…”

Section: -In the First Paragraph The Authors Stated That "Here We Dmentioning

confidence: 99%

“…It is probably due to higher ACC expression leading to malonyl-CoA production, which inhibits L-CPT1 and therefore reduces beta oxidation activity. We have included this in the Discussion section in the new version of the manuscript (page 16, ln [18][19][20]. We are not certain about the mechanisms by which the expression and activity of PPARα at 7 days is increased.…”

mentioning

confidence: 99%

“…Please be more précised as this was shown only after 14-day fructose supplementation. We have modified the sentence, and added some discussion on fructose effects at 7 days (pg 16, ln [18][19][20] of the new version of the manuscript). -Page 16: Please rephrase following statement: "Thus, we were disappointed that fructose incubation of FaO cells, despite reducing PPARα expression, did not reduce SIRT1 and NAMPT.…”

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confidence: 99%

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Liquid fructose downregulates Sirt1 expression and activity and impairs the oxidation of fatty acids in rat and human liver cells

Rebollo

Roglans

Baena

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Fructose ingestion is associated with the production of hepatic steatosis and hypertriglyceridaemia. For fructose to attain these effects in rats, simultaneous induction of fatty acid synthesis and inhibition of fatty acid oxidation is required. We aimed to determine the mechanism involved in the inhibition of fatty acid oxidation by fructose and whether this effect occurs also in human liver cells. Female rats were supplemented or not with liquid fructose (10% w/v) for 7 or 14 days; rat (FaO) and human (HepG2) hepatoma cells, and human hepatocytes were incubated with fructose 25 mM for 24 hours. The expression and activity of the enzymes and transcription factors relating to fatty acid betaoxidation were evaluated. Fructose inhibited the activity of fatty acid beta-oxidation only in livers of 14-day fructose-supplemented rats, as well as the expression and activity of peroxisome proliferator activated receptor alpha (PPARalpha). Similar results were observed in FaO and ownregulation was not due to an osmotic effect or to an increase in protein-phosphatase 2A activity caused by fructose. Rather, it was related to increased content in liver of inactive, acetylated peroxisome proliferator activated receptor gamma coactivator 1alpha, due to a reduction in sirtuin 1 expression and activity. In conclusion, fructose inhibits liver fatty acid oxidation by reducing PPARalpha expression and activity, both in rat and human liver cells, by a mechanism involving sirtuin 1 down-regulation.Response to Reviewers: Reviewer #1: Major points: 1.In order for the reader to comprehend the nutritional setting in which the changes are being observed, far more detail needs to be included to support/strengthen table 1. Details on the nutritional content of the diet must be included (% calories from fat etc..). In the same sense, it would be useful to see the data presented as total calories consumed from diet vs fructose in drinking water. In this study the rats received a regular diet (Teklad Global 2018 Rodent Diet, fromHarlan Teklad), that provided 18% calories from fat, 24% from protein and 58% from carbohydrate. This information has been included in the new version of the manuscript (Materials and Methods section, pg 5, ln 22-23). Regarding the calories consumed from diet or from fructose, we calculated the data from the area under the curve of food or drink consumption in g or ml/days/cage (containing two rats). Our results are the following: As we already stated in our first version of the manuscript, "rats increased their calorie intake in a similar way at 7 (x1.24-fold) and 14 days (x1.27-fold), mainly due to an increase in fructose calories (x1.37 and x1.39-fold at 7 and 14 days, respectively), which was not compensated by a reduction in the ingestion of solid food". Perhaps it was not clear enough, so we have rephrased the sentence (pg 11, ln 8-13): "rats increased their calorie intake in a similar way, from 726.4 to 904.4 kcal/7days/2 rats (increase of 1.24-fold) and from 1609.6 to 2052.4 kcal/14days/2 rats (x1.27...

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Effect of fructose on the phosphorylation of AMP‐activated protein kinase and acetyl‐CoA carboxylase in HepG2 cells stimulated with placental lactogen

Mukai

Hoshi

Sato

2016

Birth Defects Research Pt B

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Liver AMP/ATP ratio and fructokinase expression are related to gender differences in AMPK activity and glucose intolerance in rats ingesting liquid fructose

Cited by 87 publications

References 44 publications

Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK

Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK

Liquid fructose downregulates Sirt1 expression and activity and impairs the oxidation of fatty acids in rat and human liver cells

Effect of fructose on the phosphorylation of AMP‐activated protein kinase and acetyl‐CoA carboxylase in HepG2 cells stimulated with placental lactogen

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