Vitamin A status affects weight gain and hepatic glucose metabolism in rats fed a high-fat diet

2019 ◽  
Vol 97 (5) ◽  
pp. 545-553 ◽  
Author(s):  
Heqian Kuang ◽  
Cheng-hsin Wei ◽  
Tiannan Wang ◽  
Jennifer Eastep ◽  
Yang Li ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Vitamin A ◽  
Insulin Receptor ◽  
High Fat Diet ◽  
Glycogen Synthase ◽  
Mitogen Activated Protein Kinase ◽  
High Fat ◽  
Expression Levels ◽  
Hepatic Expression ◽  
Hepatic Glucose

Whether vitamin A (VA) has a role in the development of metabolic abnormalities associated with intake of a high-fat diet (HFD) is unclear. Sprague–Dawley rats after weaning were fed an isocaloric VA sufficient HFD (VAS-HFD) or a VA deficient HFD (VAD-HFD) for 8 weeks. Body mass, food intake, liver and adipose tissue mass, and the hepatic expression levels of key proteins for metabolism were determined. VAD-HFD rats had lower body, liver, and epididymal fat mass than VAS-HFD rats. VAD-HFD rats had lower hepatic protein expression levels of cytochrome P450 26A1, glucokinase, and phosphoenolpyruvate carboxykinase than VAS-HFD rats. VAD-HFD rats had higher protein levels of glycogen synthase kinase (GSK)-3α and lower levels of GSK-3β, but not glycogen synthase, than VAS-HFD rats. VAD-HFD rats had higher hepatic levels of insulin receptor substrate-1 (IRS-1), insulin receptor β-subunit, mitogen-activated protein kinase proteins, and peroxisome proliferator-activated receptor-gamma coactivator 1α mRNA, and lower level of IRS-2 protein than VAS-HFD rats. These results indicate that in a HFD setting, VA deficiency attenuated HFD-induced obesity, and VA status altered the expression levels of proteins required for glucose metabolism and insulin signaling. We conclude that VA status contributes to the regulation of hepatic glucose and lipid metabolism in a HFD setting, and may regulate hepatic carbohydrate metabolism.

Combined Prednisolone Treatment and a High-Fat Diet in Mice Both Induce Hyperglycemia, but Alter Hepatic Glucose Metabolism Differentially

2011 ◽  
pp. P3-390-P3-390
Author(s):  
Anke J Laskewitz ◽  
Theo H van Dijk ◽  
Wim H Dokter ◽  
Marie-Jose van Lierop ◽  
Aldo Grefhorst ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
High Fat Diet ◽  
High Fat ◽  
Hepatic Glucose Metabolism ◽  
Prednisolone Treatment ◽  
Hepatic Glucose

Abstract 15783: Reduction in Hepatic Tristetraprolin Increases Oxidative Metabolism and Protects Against High-Fat Diet Induced Diabetes

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jason S Shapiro ◽  
Konrad T Sawicki ◽  
Sumeyye Yar ◽  
Chunlei Chen ◽  
Hossein Ardehali
Keyword(s):  
Glucose Metabolism ◽  
Oxidative Metabolism ◽  
High Fat Diet ◽  
Glucose Oxidation ◽  
Fold Increase ◽  
Type Ii Diabetes Mellitus ◽  
High Fat ◽  
Hepatic Expression ◽  
Novel Treatments ◽  
Increased Risk

Introduction: Type II diabetes mellitus (T2DM) is a growing health problem affecting over 29 million Americans and individuals with T2DM have increased mortality after myocardial infarction and stroke. Thus, it is imperative to find novel treatments for diabetes to offset the increased risk of cardiovascular disease (CVD) related mortality. Tristetraprolin (TTP) is an mRNA binding protein first identified as an insulin responsive gene. It binds to AU-rich elements (AREs) in the 3’ untranslated region (UTR) of certain transcripts and promotes their degradation. Reduced TTP expression has been observed in human patients with obesity and insulin resistance, and computational analysis suggests that TTP may bind to and degrade the mRNA of key enzymes involved in glucose oxidation. Thus, we hypothesized that downregulation of TTP would increase glucose oxidation and protect against T2DM. Results: We found hepatic expression of TTP to be decreased in diabetic mice. Using an in silico analysis to identify mRNAs that are targeted by TTP and play a role in glucose metabolism, we identified the pyruvate dehydrogenase-E2 subunit (PDH-E2) to contain several conserved TTP binding sites in its 3’ UTR. PDH-E2 expression was significantly increased (mRNA > 1.4-fold; protein > 2-fold) in hepatocytes isolated from liver-specific TTP knockout (KO) mice. Furthermore, measurement of PDH-E2 mRNA stability showed that PDH-E2 mRNA is significantly stabilized with TTP deletion, indicating that TTP regulates PDH-E2 mRNA. We then assessed whether the regulation of PDH-E2 by TTP alters glucose metabolism. Using Seahorse, we found a 1.7-fold increase in oxidative metabolism in TTP KO cells fed with glucose and pyruvate. This increase was reversed with siRNA mediated downregulation of PDH-E2. Systemically, liver-specific TTP KO mice fed a high-fat diet had significantly lower blood glucose levels after glucose tolerance tests and insulin tolerance tests. Conclusion: Our results suggest that a decrease in TTP protects against the development of T2DM by increasing PDH-E2 expression and subsequent glucose oxidation in the liver. Together, these data provide a novel, potential therapeutic target for T2DM, a significant modifiable risk factor contributing to CVD mortality.

scholarly journals Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice

2008 ◽  
Vol 295 (4) ◽  
pp. E904-E912 ◽  
Author(s):  
Galyna Bryzgalova ◽  
Lovisa Lundholm ◽  
Neil Portwood ◽  
Jan-Åke Gustafsson ◽  
Akhtar Khan ◽  
...  
Keyword(s):  
Body Weight ◽  
Glucose Tolerance ◽  
Plasma Levels ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
High Fat ◽  
Expression Levels ◽  
Hepatic Expression

The high-fat diet (HFD)-fed mouse is a model of obesity, impaired glucose tolerance, and insulin resistance. The main objective of this study was to elucidate the molecular mechanisms underlying the antidiabetogenic and weight-lowering effects of 17β-estradiol (E2) in this mouse model. C57BL/6 female mice (8 wk old) were fed on a HFD for 10 mo. E2, given daily (50 μg/kg sc) during the last month of feeding, decreased body weight and markedly improved glucose tolerance and insulin sensitivity. Plasma levels of insulin, leptin, resistin, and adiponectin were decreased. We demonstrated that E2 treatment decreased the expression of genes encoding resistin and leptin in white adipose tissue (WAT), whereas adiponectin expression was unchanged. Furthermore, in WAT we demonstrated decreased expression levels of sterol regulatory element-binding protein 1c (SREBP1c) and its lipogenic target genes, such as fatty acid synthase and stearoyl-CoA desaturase 1 (SCD1). In the liver, the expression levels of transcription factors such as liver X receptor α and SREBP1c were not changed by E2 treatment, but the expression of the key lipogenic gene SCD1 was reduced. This was accompanied by decreased hepatic triglyceride content. Importantly, E2 decreased the hepatic expression of glucose-6-phosphatase (G-6-Pase). We conclude that E2 treatment exerts antidiabetic and antiobesity effects in HFD mice and suggest that this is related to decreased expression of lipogenic genes in WAT and liver and suppression of hepatic expression of G-6-Pase. Decreased plasma levels of resistin probably also play an important role in this context.

scholarly journals Boehmeria niveaStimulates Glucose Uptake by Activating Peroxisome Proliferator-Activated Receptor Gamma in C2C12 Cells and Improves Glucose Intolerance in Mice Fed a High-Fat Diet

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sung Hee Kim ◽  
Mi Jeong Sung ◽  
Jae Ho Park ◽  
Hye Jeong Yang ◽  
Jin-Taek Hwang
Keyword(s):  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Transcriptional Activity ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Levels

We examined the antidiabetic property ofBoehmeria nivea(L.) Gaud. Ethanolic extract ofBoehmeria nivea(L.) Gaud. (EBN) increased the uptake of 2-[N-(nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose in C2C12 myotubes. To examine the mechanisms underlying EBN-mediated increase in glucose uptake, we examined the transcriptional activity and expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), a pivotal target for glucose metabolism in C2C12 myotubes. We found that the EBN increased both the transcriptional activity and mRNA expression levels of PPAR-γ. In addition, we measured phosphorylation and expression levels of other targets of glucose metabolism, such as AMP-activated protein kinase (AMPK) and protein kinase B (Akt/PKB). We found that EBN did not alter the phosphorylation or expression levels of these proteins in a time- or dose-dependent manner, which suggested that EBN stimulates glucose uptake through a PPAR-γ-dependent mechanism. Further, we investigated the antidiabetic property of EBN using mice fed a high-fat diet (HFD). Administration of 0.5% EBN reduced the HFD-induced increase in body weight, total cholesterol level, and fatty liver and improved the impaired fasting glucose level, blood insulin content, and glucose intolerance. These results suggest that EBN had an antidiabetic effect in cell culture and animal systems and may be useful for preventing diabetes.

scholarly journals Effect of a high-fat diet on the hepatic expression of nuclear receptors and their target genes: relevance to drug disposition

2015 ◽  
Vol 113 (3) ◽  
pp. 507-516 ◽  
Author(s):  
Ragia H. Ghoneim ◽  
Emilienne T. Ngo Sock ◽  
Jean-Marc Lavoie ◽  
Micheline Piquette-Miller
Keyword(s):  
Nuclear Receptors ◽  
High Fat Diet ◽  
Target Genes ◽  
Drug Disposition ◽  
Fold Increase ◽  
High Fat ◽  
Expression Levels ◽  
Hepatic Expression ◽  
The Impact ◽  
Fat Feeding

More than 1·4 billion individuals are overweight or obese worldwide. While complications often require therapeutic intervention, data regarding the impact of obesity on drug disposition are scarce. As the influence of diet-induced obesity on drug transport and metabolic pathways is currently unclear, the objective of the present study was to investigate the effect of high fat feeding for 13 weeks in female Sprague–Dawley rats on the hepatic expression of the nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), liver X receptor (LXR) and farnesoid X receptor (FXR) and several of their target genes. We hypothesised that high fat feeding would alter the gene expression of major hepatic transporters through a dysregulation of the expression of the nuclear receptors. The results demonstrated that, along with a significant increase in body fat and weight, a high-fat diet (HFD) induced a significant 2-fold increase in the expression of PXR as well as a 2-, 5- and 2·5-fold increase in the hepatic expression of the PXR target genes Abcc2, Abcb1a and Cyp3a2, respectively (P< 0·05). The expression levels of FXR were significantly increased in rats fed a HFD in addition to the increase in the expression levels of FXR target genes Abcb11 and Abcb4. The expression levels of both LXRα and LXRβ were slightly but significantly increased in rats fed a HFD, and the expression levels of their target genes Abca1 and Abcg5, but not Abcg8, were significantly increased. The expression of the nuclear receptor CAR was not significantly altered between the groups. This suggests that a HFD may induce changes in the hepatobiliary transport and metabolism of endogenous and exogenous compounds.

scholarly journals Obesity and binge alcohol intake are deadly combination to induce steatohepatitis: A model of high-fat diet and binge ethanol intake

2020 ◽  
Vol 26 (4) ◽  
pp. 586-594 ◽  
Author(s):  
Seonghwan Hwang ◽  
Tianyi Ren ◽  
Bin Gao
Keyword(s):  
Liver Injury ◽  
Binge Drinking ◽  
Mouse Models ◽  
High Fat Diet ◽  
Neutrophil Infiltration ◽  
Mitogen Activated Protein Kinase ◽  
High Fat ◽  
Hepatic Expression ◽  
Underlying Mechanisms ◽  
Binge Ethanol

Obesity and binge drinking often coexist and work synergistically to promote steatohepatitis; however, the underlying mechanisms remain obscure. In this mini-review, we briefly summarize clinical evidence of the synergistical effect of obesity and heavy drinking on steatohepatitis and discuss the underlying mechanisms obtained from the study of several mouse models. High-fat diet (HFD) feeding and binge ethanol synergistically induced steatohepatitis and fibrosis in mice with significant intrahepatic neutrophil infiltration; such HFD-plus-ethanol treatment markedly up-regulated the hepatic expression of many chemokines with the highest fold (approximately 30-fold) induction of chemokine (C-X-C motif) ligand 1 (<i>Cxcl1</i>), which contributes to hepatic neutrophil infiltration and liver injury. Furthermore, HFD feeding activated peroxisome proliferator-activated receptor gamma that subsequently inhibited CXCL1 upregulation in hepatocytes, thereby forming a negative feedback loop to prevent neutrophil overaction; whereas binge ethanol blocked this loop and then exacerbated CXCL1 elevation, neutrophil infiltration, and liver injury. Interestingly, inflamed mouse hepatocytes attracted neutrophils less effectively than inflamed human hepatocytes due to the lower induction of CXCL1 and the lack of the interleukin (IL)-8 gene in the mouse genome, which may be one of the reasons for difficulty in development of mouse models of alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH). Hepatic overexpression of <i>Cxcl1</i> and/or IL-8 promoted steatosis-to-NASH progression in HFD-fed mice by inducing neutrophil infiltration, oxidative stress, hepatocyte death, fibrosis, and p38 mitogen-activated protein kinase activation. Collectively, obesity and binge drinking synergistically promote steatohepatitis via the induction of CXCL1 and subsequent hepatic neutrophil infiltration.

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