scholarly journals Lyophilized Maqui (Aristotelia chilensis) Berry Administration Suppresses High-Fat Diet-Induced Liver Lipogenesis through the Induction of the Nuclear Corepressor SMILE

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 637
Author(s):  
Viviana Sandoval ◽  
Hèctor Sanz-Lamora ◽  
Pedro F. Marrero ◽  
Joana Relat ◽  
Diego Haro
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Insulin Response ◽  
High Fat ◽  
Positive Effects ◽  
Triglyceride Accumulation ◽  
Ectopic Lipids ◽  
The Impact

The liver is one of the first organs affected by accumulated ectopic lipids. Increased de novo lipogenesis and excessive triglyceride accumulation in the liver are hallmarks of nonalcoholic fatty liver disease (NAFLD) and are strongly associated with obesity, insulin resistance, and type 2 diabetes. Maqui dietary supplemented diet-induced obese mice showed better insulin response and decreased weight gain. We previously described that these positive effects of maqui are partially due to an induction of a brown-like phenotype in subcutaneous white adipose tissue that correlated with a differential expression of Chrebp target genes. In this work, we aimed to deepen the molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance focusing on liver metabolism. Our results showed that maqui supplementation decreased hepatic steatosis caused by a high-fat diet. Changes in the metabolic profile include a downregulation of the lipogenic liver X receptor (LXR) target genes and of fatty acid oxidation gene expression together with an increase in the expression of small heterodimer partner interacting leucine zipper protein (Smile), a corepressor of the nuclear receptor family. Our data suggest that maqui supplementation regulates lipid handling in liver to counteract the metabolic impact of a high-fat diet.

scholarly journals PKCε contributes to lipid-induced insulin resistance through cross talk with p70S6K and through previously unknown regulators of insulin signaling

2018 ◽  
Vol 115 (38) ◽  
pp. E8996-E9005 ◽  
Author(s):  
Brandon M. Gassaway ◽  
Max C. Petersen ◽  
Yulia V. Surovtseva ◽  
Karl W. Barber ◽  
Joshua B. Sheetz ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Phosphorylation ◽  
Cross Talk ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Large Scale ◽  
Kinase Assay ◽  
Hepatic Insulin Resistance ◽  
High Fat ◽  
The Impact

Insulin resistance drives the development of type 2 diabetes (T2D). In liver, diacylglycerol (DAG) is a key mediator of lipid-induced insulin resistance. DAG activates protein kinase C ε (PKCε), which phosphorylates and inhibits the insulin receptor. In rats, a 3-day high-fat diet produces hepatic insulin resistance through this mechanism, and knockdown of hepatic PKCε protects against high-fat diet-induced hepatic insulin resistance. Here, we employed a systems-level approach to uncover additional signaling pathways involved in high-fat diet-induced hepatic insulin resistance. We used quantitative phosphoproteomics to map global in vivo changes in hepatic protein phosphorylation in chow-fed, high-fat–fed, and high-fat–fed with PKCε knockdown rats to distinguish the impact of lipid- and PKCε-induced protein phosphorylation. This was followed by a functional siRNA-based screen to determine which dynamically regulated phosphoproteins may be involved in canonical insulin signaling. Direct PKCε substrates were identified by motif analysis of phosphoproteomics data and validated using a large-scale in vitro kinase assay. These substrates included the p70S6K substrates RPS6 and IRS1, which suggested cross talk between PKCε and p70S6K in high-fat diet-induced hepatic insulin resistance. These results identify an expanded set of proteins through which PKCε may drive high-fat diet-induced hepatic insulin resistance that may direct new therapeutic approaches for T2D.

Synergistic effect of sea cucumber saponins and EPA-enriched phospholipids on insulin resistance in high-fat diet-induced obese mice

2019 ◽  
Vol 10 (7) ◽  
pp. 3955-3964 ◽  
Author(s):  
Xiu-Qing Han ◽  
Ling-Yu Zhang ◽  
Lin Ding ◽  
Hao-Hao Shi ◽  
Chang-Hu Xue ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Synergistic Effect ◽  
High Fat Diet ◽  
Sea Cucumber ◽  
Insulin Response ◽  
Obese Mice ◽  
High Fat

The combination of sea cucumber saponins (SCS) and EPA-PL contributed to a synergistic effect on alleviating the obesity-related insulin resistance due to the amelioration of an inflammation centric peripheral insulin response.

MiR-425-5p Regulates Glucagon-like Peptide-1 Production and Affects Blood Glucose Levels in High-fat Diet-fed Mice

2021 ◽  
Author(s):  
Lirui Wei ◽  
Xuenan Zhao ◽  
Feng Guo ◽  
Fengjiao Huang ◽  
Yanyan Zhao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Protein Level ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Tolerance Test ◽  
Control Group ◽  
High Fat ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract BackgroundIn modern society, obesity has become a global problem with resulting in metabolic disorders and poses high risk for type 2 diabetes mellitus (T2DM). The glucagon-like peptide-1 (GLP-1) has been taken as an effective drug for the therapy of T2DM and obesity. In the present study, the regulatory roles and molecular mechanisms of miR-425-5p in GLP-1 secretion in high-fat diet (HFD)-induced diabetic mice were explored. MethodsOral glucose tolerance test and insulin tolerance test were performed to assess glucose metabolism and GLP-1 and LPS levels. Quantitative real time polymerase chain reaction (qRT-PCR) was employed to detect the expression of LPS, GLP-1, GLP-1 receptors, miR-425-5p, phosphatase and tensin homology (PTEN), proglucagon, p65 and β-catenin. Western blot was performed to determine the expression of proglucagon, p65, β-catenin and PTEN. ResultsThe results showed that plasma GLP-1 level was negatively correlated with plasma LPS level in HFD-fed mice, and miR-425-5p expression and LPS level were up-regulated in the ileal fluid compared with control groups. LPS injection boosted miR-425-5p expression in ileum. MiR-425-5p ameliorated glucose intolerance and insulin resistance in HFD-fed mice by increasing GLP-1 secretion. Furthermore, p65 protein level in the cytoplasmic and nuclear in the ileum of HFD-fed mice was increased compared with the control group. MiR-425-5p agomir elevated nuclear β-catenin protein level, but reduced PTEN protein level in HFD-fed mice compared with HFD-fed mice treated with the miR-425-5p antagomir. ConclusionsOur results suggest that miR-425-5p promotes GLP-1 secretion and improves glucose tolerance and insulin resistance in high-fat diet-fed mice.

Effect of synbiotic supplementation on asprosin level in high fat diet-induced metabolic disorder in pregnant rats

2021 ◽  
pp. 1-10
Author(s):  
Mehrdad Naghizadeh ◽  
Mansour Karajibani ◽  
Hamed Fanaei ◽  
Farzaneh Montazerifar ◽  
Alireza Dashipour
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Lipid Profile ◽  
Total Cholesterol ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
High Fat ◽  
Pregnant Rats ◽  
Synbiotic Supplementation ◽  
The Impact

Synbiotic supplementation can improve metabolic disorders. The aim of this study was to assess the impact of synbiotic supplementation on the levels of asprosin, lipid profile, glucose, and insulin resistance in pregnant rats fed a high-fat diet (HFD). Rats were divided into three groups: control group (fed base chow), HFD group, and HFD + synbiotic group. Levels of blood glucose, total cholesterol, triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, and asprosin levels were measured. Birth weight of offspring in the HFD + synbiotic group was significantly lower than in the HFD group. Similarly, serum asprosin, insulin, insulin resistance, TG and total cholesterol levels in the HFD + symbiotic group were significantly lower than in the HFD group. Asprosin levels had a significant and positive correlation between food intake in the first ten days of the experiment and gestation period, fasting blood sugar (FBS), TG, and homeostatic model assessment (HOMA) index. Moreover, asprosin levels had a significant and negative correlation with HDL and insulin levels. Results showed, synbiotic supplementation has beneficial effects on obese animals and improves weight gain during pregnancy, pup birth weight, FBS, insulin resistance and lipid profile. These advantages of synbiotic supplementation could be mediated by reducing serum asprosin levels.

scholarly journals Deepure Tea Improves High Fat Diet-Induced Insulin Resistance and Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jing-Na Deng ◽  
Juan Li ◽  
Hong-Na Mu ◽  
Yu-Ying Liu ◽  
Ming-Xia Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Fatty Acid Synthesis ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
High Fat ◽  
The Metabolic Syndrome

This study was to explore the protective effects of Deepure tea against insulin resistance and hepatic steatosis and elucidate the potential underlying molecular mechanisms. C57BL/6 mice were fed with a high fat diet (HFD) for 8 weeks to induce the metabolic syndrome. In the Deepure tea group, HFD mice were administrated with Deepure tea at 160 mg/kg/day by gavage for 14 days. The mice in HFD group received water in the same way over the same period. The age-matched C57BL/6 mice fed with standard chow were used as normal control. Compared to the mice in HFD group, mice that received Deepure tea showed significantly reduced plasma insulin and improved insulin sensitivity. Deepure tea increased the expression of insulin receptor substrate 2 (IRS-2), which plays an important role in hepatic insulin signaling pathway. Deepure tea also led to a decrease in hepatic fatty acid synthesis and lipid accumulation, which were mediated by the downregulation of sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthesis (FAS), and acetyl-CoA carboxylase (ACC) proteins that are involved in liver lipogenesis. These results suggest that Deepure tea may be effective for protecting against insulin resistance and hepatic steatosis via modulating IRS-2 and downstream signaling SREBP-1c, FAS, and ACC.

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 Tofogliflozin Improves Insulin Resistance in Skeletal Muscle and Accelerates Lipolysis in Adipose Tissue in Male Mice

Endocrinology ◽  
2015 ◽  
Vol 157 (3) ◽  
pp. 1029-1042 ◽  
Author(s):  
Atsushi Obata ◽  
Naoto Kubota ◽  
Tetsuya Kubota ◽  
Masahiko Iwamoto ◽  
Hiroyuki Sato ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Glucose Uptake ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
The Body ◽  
High Fat ◽  
Ad Libitum

Abstract Sodium glucose cotransporter 2 inhibitors have attracted attention as they exert antidiabetic and antiobesity effects. In this study, we investigated the effects of tofogliflozin on glucose homeostasis and its metabolic consequences and clarified the underlying molecular mechanisms. C57BL/6 mice were fed normal chow containing tofogliflozin (0.005%) for 20 weeks or a high-fat diet containing tofogliflozin (0.005%) for 8 weeks ad libitum. In addition, the animals were pair-fed in relation to controls to exclude the influence of increased food intake. Tofogliflozin reduced the body weight gain, mainly because of fat mass reduction associated with a diminished adipocyte size. Glucose tolerance and insulin sensitivity were ameliorated. The serum levels of nonesterified fatty acid and ketone bodies were increased and the respiratory quotient was decreased in the tofogliflozin-treated mice, suggesting the acceleration of lipolysis in the white adipose tissue and hepatic β-oxidation. In fact, the phosphorylation of hormone-sensitive lipase and the adipose triglyceride lipase protein levels in the white adipose tissue as well as the gene expressions related to β-oxidation, such as Cpt1α in the liver, were significantly increased. The hepatic triglyceride contents and the expression levels of lipogenic genes were decreased. Pair-fed mice exhibited almost the same results as mice fed an high-fat diet ad libitum. Moreover, a hyperinsulinemic-euglycemic clamp revealed that tofogliflozin improved insulin resistance by increasing glucose uptake, especially in the skeletal muscle, in pair-fed mice. Taken together, these results suggest tofogliflozin ameliorates insulin resistance and obesity by increasing glucose uptake in skeletal muscle and lipolysis in adipose tissue.

scholarly journals Integrated analysis of differentially expressed long noncoding RNAs and mRNAs associated with high-fat diet-induced hepatic insulin resistance in mice

2020 ◽  
Author(s):  
Zengyuan Zhou ◽  
Xue Zhao ◽  
Liang Chen ◽  
Yuzheng Li ◽  
Zhao Chen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Potential Functions ◽  
Long Noncoding Rnas ◽  
Hepatic Insulin Resistance ◽  
Integrated Analysis ◽  
High Fat ◽  
Glycolipid Metabolism

Abstract Background: Hepatic insulin resistance (IR) is an early pathological characteristic of many metabolic diseases, such as type 2 diabetes. Long noncoding RNAs (lncRNAs) have been identified as mediators of IR and related diseases. However, the roles of lncRNAs in hepatic IR remain largely unknown. Method: High-throughput sequencing was performed on ten liver tissue samples from five normal diet (ND)-fed mice and five high-fat diet (HFD)-induced hepatic IR mice, respectively. lncRNAs and mRNAs that were differentially expressed (DE) between the two groups were identified by bioinformatic analyses. Seven DE lncRNAs were validated by quantitative real-time PCR (q-PCR). The potential functions of the DE lncRNAs were predicted by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of target genes. In addition, integrated analysis was performed for the DE lncRNAs and mRNAs to predict their interaction relationships.Results: A total of 232 DE lncRNAs were identified in the HFD-induced hepatic IR mice compared with the ND-fed mice. These DE lncRNAs included 108 upregulated and 124 downregulated lncRNAs, and 7 of the DE lncRNAs were validated by q-PCR. In addition, 291 DE mRNAs including 166 upregulated and 125 downregulated mRNAs were identified in the HFD group. Furthermore, target genes of the DE lncRNAs were predicted, and functional enrichment results showed that the enriched genes were involved in IR- and glycolipid metabolism-related processes. Additionally, the coexpression network was also constructed to further reflect the potential functions of the DE lncRNAs.Conclusion: The study describes the expression profiles of lncRNAs and mRNAs and the functional networks involved in HFD-induced hepatic IR. These findings may provide a new perspective for the study of lncRNAs in hepatic IR- and glycolipid metabolism-related diseases.

scholarly journals Expressing the Human Cholesteryl Ester Transfer Protein Minigene Improves Diet-Induced Fatty Liver and Insulin Resistance in Female Mice

2022 ◽  
Vol 12 ◽  
Author(s):  
Lin Zhu ◽  
Julia An ◽  
Sivaprakasam Chinnarasu ◽  
Thao Luu ◽  
Yasminye D. Pettway ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Target Genes ◽  
Metabolic Adaptation ◽  
Liver Cholesterol ◽  
Wild Type ◽  
High Fat

Mounting evidence has shown that CETP has important physiological roles in adapting to chronic nutrient excess, specifically, to protect against diet-induced insulin resistance. However, the underlying mechanisms for the protective roles of CETP in metabolism are not yet clear. Mice naturally lack CETP expression. We used transgenic mice with a human CETP minigene (huCETP) controlled by its natural flanking region to further understand CETP-related physiology in response to obesity. Female huCETP mice and their wild-type littermates were fed a high-fat diet for 6 months. Blood lipid profile and liver lipid metabolism were studied. Insulin sensitivity was analyzed with euglycemic-hyperinsulinemic clamp studies combined with 3H-glucose tracer techniques. While high-fat diet feeding induced obesity for huCETP mice and their wild-type littermates lacking CETP expression, insulin sensitivity was higher for female huCETP mice than for their wild-type littermates. There was no difference in insulin sensitivity for male huCETP mice vs. littermates. The increased insulin sensitivity in females was largely caused by the better insulin-mediated suppression of hepatic glucose production. In huCETP females, CETP in the circulation decreased HDL-cholesterol content and increased liver cholesterol uptake and liver cholesterol and oxysterol contents, which was associated with the upregulation of LXR target genes in long-chain polyunsaturated fatty acid biosynthesis and PPARα target genes in fatty acid β-oxidation in the liver. The upregulated fatty acid β-oxidation may account for the improved fatty liver and liver insulin action in female huCETP mice. This study provides further evidence that CETP has beneficial physiological roles in the metabolic adaptation to nutrient excess by promoting liver fatty acid oxidation and hepatic insulin sensitivity, particularly for females.

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