Peripancreatic adipose tissue protects against high-fat-diet-induced hepatic steatosis and insulin resistance in 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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The Effects of Poncirus fructus on Insulin Resistance and the Macrophage-Mediated Inflammatory Response in High Fat Diet-Induced Obese Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20122858 ◽

2019 ◽

Vol 20 (12) ◽

pp. 2858 ◽

Cited By ~ 3

Author(s):

Mia Kim ◽

Mi Hyeon Seol ◽

Byung-Cheol Lee

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Kupffer Cells ◽

High Fat Diet ◽

Inflammatory Responses ◽

Low Grade ◽

Obese Mice ◽

High Fat ◽

Epididymal Fat

Obesity is a chronic low-grade inflammatory condition in which hypertrophied adipocytes and adipose tissue immune cells, mainly macrophages, contribute to increased circulating levels of proinflammatory cytokines. Obesity-associated chronic low-grade systemic inflammation is considered a focal point and a therapeutic target in insulin resistance and metabolic diseases. We evaluate the effect of Poncirus fructus (PF) on insulin resistance and its mechanism based on inflammatory responses in high-fat diet (HFD)-induced obese mice. Mice were fed an HFD to induce obesity and then administered PF. Body weight, epididymal fat and liver weight, glucose, lipid, insulin, and histologic characteristics were evaluated to determine the effect of PF on insulin resistance by analyzing the proportion of macrophages in epididymal fat and liver and measured inflammatory gene expression. PF administration significantly decreased the fasting and postprandial glucose, fasting insulin, HOMA-IR, total-cholesterol, triglycerides, and low-density lipoprotein cholesterol levels. The epididymal fat tissue and liver showed a significant decrease of fat accumulation in histological analysis. PF significantly reduced the number of adipose tissue macrophages (ATMs), F4/80+ Kupffer cells, and CD68+ Kupffer cells, increased the proportion of M2 phenotype macrophages, and decreased the gene expression of inflammatory cytokines. These results suggest that PF could be used to improve insulin resistance through modulation of macrophage-mediated inflammation and enhance glucose and lipid metabolism.

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2011-P: Totum-63 Lowers Adipose Tissue Inflammation and Reverses Both Hepatic Steatosis and Insulin Resistance in High-Fat Diet-Induced Obese Mice

Diabetes ◽

10.2337/db19-2011-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 2011-P

Author(s):

HENDRIK JOHANNES VAN DER ZANDE ◽

ANNA ZAWISTOWSKA-DENIZIAK ◽

FRANK OTTO ◽

VIVIEN CHAVANELLE ◽

SEBASTIEN PELTIER ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Adipose Tissue Inflammation ◽

Obese Mice ◽

High Fat ◽

Tissue Inflammation

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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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Abstract 6260: Up-Regulated Expression of MicroRNA-143 in Association with Obesity in the Adipose Tissue of Mice Fed High Fat Diet

Circulation ◽

10.1161/circ.118.suppl_18.s_1169-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Rieko Takanabe ◽

Koh Ono ◽

Tomohide Takaya ◽

Takahiro Horie ◽

Hiromichi Wada ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Body Weight ◽

Adipose Tissue ◽

High Fat Diet ◽

Control Cell ◽

High Fat ◽

Expression Levels ◽

Mesenteric Fat ◽

Regulated Expression

Obesity is the result of an expansion and increase in the number of individual adipocytes. Since changes in gene expression during adipocyte differentiation and hypertrophy are closely associated with insulin resistance and cardiovascular diseases, further insight into the molecular basis of obesity is needed to better understand obesity-associated diseases. MicroRNAs (miRNAs) are approximately 17–24nt single stranded RNA, that post-transcriptionally regulate gene expression. MiRNAs control cell growth, differentiation and metabolism, and may be also involved in pathogenesis and pathophysiology of diseases. It has been proposed that miR-143 plays a role in the differentiation of preadipocytes into mature adipocytes in culture. However, regulated expression of miR-143 in the adult adipose tissue during the development of obesity in vivo is unknown. To solve this problem, C57BL/6 mice were fed with either high-fat diet (HFD) or normal chow (NC). Eight weeks later, severe insulin resistance was observed in mice on HFD. Body weight increased by 35% and the mesenteric fat weight increased by 3.3-fold in HFD mice compared with NC mice. We measured expression levels of miR-143 in the mesenteric fat tissue by real-time PCR and normalized with those of 5S ribosomal RNA. Expression of miR-143 in the mesenteric fat was significantly up-regulated (3.3-fold, p<0.05) in HFD mice compared to NC mice. MiR-143 expression levels were positively correlated with body weight (R=0.577, p=0.0011) and the mesenteric fat weight (R=0.608, p=0.0005). We also measured expression levels in the mesenteric fat of PPARγ and AP2, whose expression are deeply involved in the development of obesity, insulin resistant and arteriosclerosis. The expression levels of miR-143 were closely correlated with those of PPARγ (R=0.600, p=0.0040) and AP2 (R=0.630, p=0.0022). These findings provide the first evidence for up-regulated expression of miR-143 in the mesenteric fat of HFD-induced obese mice, which might contribute to regulated expression of genes involved in the pathophysiology of obesity.

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Identification of genes expressed differentially in subcutaneous and visceral fat of cattle, pig, and mouse

Physiological Genomics ◽

10.1152/physiolgenomics.00184.2004 ◽

2005 ◽

Vol 21 (3) ◽

pp. 343-350 ◽

Cited By ~ 34

Author(s):

Daisuke Hishikawa ◽

Yeon-Hee Hong ◽

Sang-gun Roh ◽

Hisae Miyahara ◽

Yukihiko Nishimura ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

High Fat Diet ◽

Animal Species ◽

Fat Deposition ◽

High Fat ◽

Adipose Tissues ◽

Fat Accumulation ◽

Fat Depots ◽

Visceral Adipose

The factors that control fat deposition in adipose tissues are poorly understood. It is known that visceral adipose tissues display a range of biochemical properties that distinguish them from adipose tissues of subcutaneous origin. However, we have little information on gene expression, either in relation to fat deposition or on interspecies variation in fat deposition. The first step in this study was to identify genes expressed in fat depot of cattle using the differential display RT-PCR method. Among the transcripts identified as having differential expression in the two adipose tissues were cell division cycle 42 homolog (CDC42), prefoldin-5, decorin, phosphate carrier, 12S ribosomal RNA gene, and kelch repeat and BTB domain containing 2 (Kbtbd2). In subsequent experiments, we determined the expression levels of these latter genes in the pig and in mice fed either a control or high-fat diet to compare the regulation of fat accumulation in other animal species. The levels of CDC42 and decorin mRNA were found to be higher in visceral adipose tissue than in subcutaneous adipose tissue in cattle, pig, and mice. However, the other genes studied did not show consistent expression patterns between the two tissues in cattle, pigs, and mice. Interestingly, all genes were upregulated in subcutaneous and/or visceral adipose tissues of mice fed the high-fat diet compared with the control diet. The data presented here extend our understanding of gene expression in fat depots and provide further proof that the mechanisms of fat accumulation differ significantly between animal species.

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Diethylcarbamazine citrate ameliorates insulin resistance in high-fat diet-induced obese mice via modulation of adipose tissue inflammation

International Immunopharmacology ◽

10.1016/j.intimp.2015.09.021 ◽

2015 ◽

Vol 29 (2) ◽

pp. 607-612 ◽

Cited By ~ 2

Author(s):

Mahmoud Abdel-Latif

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

High Fat Diet ◽

Adipose Tissue Inflammation ◽

Obese Mice ◽

High Fat ◽

Tissue Inflammation ◽

Diethylcarbamazine Citrate

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The Effect of a Sustained High-Fat Diet on the Metabolism of White and Brown Adipose Tissue and Its Impact on Insulin Resistance: A Selected Time Point Cross-Sectional Study

International Journal of Molecular Sciences ◽

10.3390/ijms222413639 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13639

Author(s):

Babu Raja Maharjan ◽

Susan V. McLennan ◽

Christine Yee ◽

Stephen M. Twigg ◽

Paul F. Williams

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

High Fat Diet ◽

Liver Fat ◽

Lipid Deposition ◽

High Fat ◽

Dynamic Changes ◽

Gene Markers ◽

Fat Depots ◽

Brown Adipose

(1) Background: studies on the long-term dynamic changes in fat depot metabolism in response to a high-fat diet (HFD) on hepatic lipid deposition and insulin resistance are sparse. This study investigated the dynamic changes produced by HFD and the production of dysfunctional fat depots on insulin resistance and liver lipid metabolism. (2) Methods: mice fed a chow or HFD (45% kcal fat) diet had three fat depots, liver, and blood collected at 6, 10, 20, and 30 weeks. Anthropometric changes and gene markers for adipogenesis, thermogenesis, ECM remodeling, inflammation, and tissue insulin resistance were measured. (3) Results: early responses to the HFD were increased body weight, minor deposition of lipid in liver, increased adipocyte size, and adipogenesis. Later changes were dysfunctional adipose depots, increased liver fat, insulin resistance (shown by changes in ITT) accompanied by increased inflammatory markers, increased fibrosis (fibrosis > 2-fold, p < 0.05 from week 6), and the presence of crown cells in white fat depots. Later, changes did not increase thermogenic markers in response to the increased calories and decreased UCP1 and PRDM16 proteins in WAT. (4) Conclusions: HFD feeding initially increased adipocyte diameter and number, but later changes caused adipose depots to become dysfunctional, restricting adipose tissue expansion, changing the brown/beige ratios in adipose depots, and causing ectopic lipid deposition and insulin resistance.

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