Chardonnay Grape Seed Flour Ameliorates Hepatic Steatosis and Insulin Resistance via Altered Hepatic Gene Expression for Oxidative Stress, Inflammation, and Lipid and Ceramide Synthesis in Diet-Induced Obese Mice

Abstract Background/objectives Visceral adiposity is associated with increased diabetes risk, while expansion of subcutaneous adipose tissue may be protective. However, the visceral compartment contains different fat depots. Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot. Here, we aimed to define PAT functionality in lean and high-fat-diet (HFD)-induced obese mice. Subjects/methods Four adipose tissue depots (inguinal, mesenteric, gonadal, and peripancreatic adipose tissue) from chow- and HFD-fed male mice were compared with respect to adipocyte size (n = 4–5/group), cellular composition (FACS analysis, n = 5–6/group), lipogenesis and lipolysis (n = 3/group), and gene expression (n = 6–10/group). Radioactive tracers were used to compare lipid and glucose metabolism between these four fat depots in vivo (n = 5–11/group). To determine the role of PAT in obesity-associated metabolic disturbances, PAT was surgically removed prior to challenging the mice with HFD. PAT-ectomized mice were compared to sham controls with respect to glucose tolerance, basal and glucose-stimulated insulin levels, hepatic and pancreatic steatosis, and gene expression (n = 8–10/group). Results We found that PAT is a tiny fat depot (~0.2% of the total fat mass) containing relatively small adipocytes and many “non-adipocytes” such as leukocytes and fibroblasts. PAT was distinguished from the other fat depots by increased glucose uptake and increased fatty acid oxidation in both lean and obese mice. Moreover, PAT was the only fat depot where the tissue weight correlated positively with liver weight in obese mice (R = 0.65; p = 0.009). Surgical removal of PAT followed by 16-week HFD feeding was associated with aggravated hepatic steatosis (p = 0.008) and higher basal (p < 0.05) and glucose-stimulated insulin levels (p < 0.01). PAT removal also led to enlarged pancreatic islets and increased pancreatic expression of markers of glucose-stimulated insulin secretion and islet development (p < 0.05). Conclusions PAT is a small metabolically highly active fat depot that plays a previously unrecognized role in the pathogenesis of hepatic steatosis and insulin resistance in advanced obesity.

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Altered Hepatic Gene Expression Profiles Associated with Improved Fatty Liver, Insulin Resistance, and Intestinal Permeability after Hydroxypropyl Methylcellulose (HPMC) Supplementation in Diet-Induced Obese Mice

Journal of Agricultural and Food Chemistry ◽

10.1021/jf400545w ◽

2013 ◽

Vol 61 (26) ◽

pp. 6404-6411 ◽

Cited By ~ 9

Author(s):

Hyunsook Kim ◽

Glenn E. Bartley ◽

Scott A. Young ◽

Kun-Ho Seo ◽

Wallace Yokoyama

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Fatty Liver ◽

Intestinal Permeability ◽

Expression Profiles ◽

Hydroxypropyl Methylcellulose ◽

Gene Expression Profiles ◽

Hepatic Gene Expression ◽

Obese Mice ◽

Liver Insulin Resistance

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Flavonoid-rich Chardonnay grape seed flour supplementation ameliorates diet-induced visceral adiposity, insulin resistance, and glucose intolerance via altered adipose tissue gene expression

Journal of Functional Foods ◽

10.1016/j.jff.2015.06.039 ◽

2015 ◽

Vol 17 ◽

pp. 881-891 ◽

Cited By ~ 15

Author(s):

Kun-Ho Seo ◽

Hyunsook Kim ◽

Jung-Whan Chon ◽

Dong-Hyeon Kim ◽

Seung-Yeol Nah ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Glucose Intolerance ◽

Grape Seed ◽

Visceral Adiposity ◽

Seed Flour ◽

Adipose Tissue Gene Expression ◽

Tissue Gene Expression

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Black rice anthocyanins alleviate hyperlipidemia, liver steatosis and insulin resistance by regulating lipid metabolism and gut microbiota in obese mice

Food & Function ◽

10.1039/d1fo01394g ◽

2021 ◽

Author(s):

Haizhao Song ◽

Xinchun Shen ◽

Yang Zhou ◽

Xiaodong Zheng

Keyword(s):

Insulin Resistance ◽

Lipid Metabolism ◽

Gut Microbiota ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Liver Steatosis ◽

Obese Mice ◽

Black Rice ◽

High Fat ◽

Diet Induced Obesity

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

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Treatment with Lobeglitazone Attenuates Hepatic Steatosis in Diet-Induced Obese Mice

PPAR Research ◽

10.1155/2018/4292509 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Sorim Choung ◽

Kyong Hye Joung ◽

Bo Ram You ◽

Sang Ki Park ◽

Hyun Jin Kim ◽

...

Keyword(s):

Insulin Resistance ◽

Hepatic Steatosis ◽

Plasma Cholesterol ◽

Cholesterol Biosynthesis ◽

Peroxisome Proliferator ◽

Obese Mice ◽

Nonalcoholic Fatty Liver ◽

Hepatic Lipid ◽

Hepatic Expression ◽

Expression Of Genes

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. The peroxisome proliferator-activated receptor (PPAR) activators, thiazolidinediones, (TZDs), are insulin sensitizers used as a treatment for NAFLD. However, TZDs are a controversial treatment for NAFLD because of conflicting results regarding hepatic steatosis and fibrosis. To evaluate a possible effective drug for treatment of NAFLD, we investigated the effects of a newly developed TZD, lobeglitazone, with an emphasis on hepatic lipid metabolism. Lobeglitazone treatment for 4 weeks in high fat diet- (HFD-) induced obese mice (HL group) improved insulin resistance and glucose intolerance compared to HFD-induced obese mice (HU group). The gene levels related to hepatic gluconeogenesis also decreased after treatment by lobeglitazone. The livers of mice in the HL group showed histologically reduced lipid accumulation, with lowered total plasma cholesterol and triglyceride levels. In addition, the HL group significantly decreased the hepatic expression of genes associated with lipid synthesis, cholesterol biosynthesis, and lipid droplet development and increased the hepatic expression of genes associated with fatty acid β-oxidation, thus suggesting that lobeglitazone decreased hepatic steatosis and reversed hepatic lipid dysregulation. Livers with steatohepatitis contained increased levels of PPARγ and phosphorylated PPARγ at serine 273, leading to downregulation of expression of genes associated with insulin sensitivity. Notably, the treatment of lobeglitazone increased the protein levels of PPARα and diminished levels of PPARγ phosphorylated at serine 273, which were increased by a HFD, suggesting that induction of PPARα and posttranslational modification of PPARγ in livers by lobeglitazone might be an underlying mechanism of the improvement seen in NAFLD. Taken together, our data showed that lobeglitazone might be an effective treatment for NAFLD.

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The effects of grape seed on apoptosis-related gene expression and oxidative stress in streptozotocin-induced diabetic rats

Renal Failure ◽

10.3109/0886022x.2014.991996 ◽

2015 ◽

Vol 37 (2) ◽

pp. 192-197 ◽

Cited By ~ 8

Author(s):

Aydın Güçlü ◽

Nilüfer Yonguç ◽

Yavuz Dodurga ◽

Gülşah Gündoğdu ◽

Zuhal Güçlü ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Grape Seed ◽

Diabetic Rats ◽

Related Gene ◽

And Oxidative Stress ◽

Apoptosis Related Gene

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Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

Scientific Reports ◽

10.1038/s41598-019-51196-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Denise E. Lackey ◽

Felipe C. G. Reis ◽

Roi Isaac ◽

Rizaldy C. Zapata ◽

Dalila El Ouarrat ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Target Genes ◽

Obese Mice ◽

Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

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Selenoprotein W deficiency does not affect oxidative stress and insulin sensitivity in the skeletal muscle of high-fat diet-fed obese mice

AJP Cell Physiology ◽

10.1152/ajpcell.00064.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. C1172-C1182 ◽

Cited By ~ 3

Author(s):

Min-Gyeong Shin ◽

Hye-Na Cha ◽

Soyoung Park ◽

Yong-Woon Kim ◽

Jong-Yeon Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

High Fat Diet ◽

Control Diet ◽

In Vivo Studies ◽

Selenoprotein W ◽

Obese Mice ◽

High Fat

Selenoprotein W (SelW) is a selenium-containing protein with a redox motif found abundantly in the skeletal muscle of rodents. Previous in vitro studies suggest that SelW plays an antioxidant role; however, relatively few in vivo studies have addressed the antioxidant role of SelW. Since oxidative stress is a causative factor for the development of insulin resistance in obese subjects, we hypothesized that if SelW plays a role as an antioxidant, SelW deficiency could aggravate the oxidative stress and insulin resistance caused by a high-fat diet. SelW deficiency did not affect insulin sensitivity and H2O2 levels in the skeletal muscle of control diet-fed mice. SelW levels in the skeletal muscle were decreased by high-fat diet feeding for 12 wk. High-fat diet induced obesity and insulin resistance and increased the levels of H2O2 and oxidative stress makers, which were not affected by SelW deficiency. High-fat diet feeding increased the expression of antioxidant enzymes; however, SelW deficiency did not affect the expression levels of antioxidants. These results suggest that SelW does not play a protective role against oxidative stress and insulin resistance in the skeletal muscle of high-fat diet-fed obese mice.

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