White Adipose Tissue Vegf Gene Expression Is Increased By Exercise And Predicts Improvements In Insulin Resistance In 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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Proteome and gene expression analysis in white adipose tissue of diet-induced obese mice

10.5353/th_b3936743 ◽

2007 ◽

Author(s):

Wing-yan So

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Expression Analysis ◽

White Adipose Tissue ◽

Gene Expression Analysis ◽

Obese Mice

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Osteocalcin improves insulin resistance and inflammation in obese mice: Participation of white adipose tissue and bone

Bone ◽

10.1016/j.bone.2017.11.020 ◽

2018 ◽

Vol 115 ◽

pp. 68-82 ◽

Cited By ~ 14

Author(s):

J.A.C. Guedes ◽

J.V. Esteves ◽

M.R. Morais ◽

T.M. Zorn ◽

D.T. Furuya

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Obese Mice

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Critical Genes in White Adipose Tissue Based on Gene Expression Profile Following Exercise

International Journal of Sports Medicine ◽

10.1055/a-0768-7866 ◽

2018 ◽

Vol 40 (01) ◽

pp. 57-61 ◽

Cited By ~ 4

Author(s):

Haitang Wang ◽

J.- Lee ◽

Ye Tian

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Signaling Pathway ◽

White Adipose Tissue ◽

Metabolic Diseases ◽

Acid Oxidation ◽

Hub Genes ◽

Network Analyses ◽

Resistance Pathway

AbstractExercise is recognized as an effective method to prevent obesity and alleviate metabolic diseases. Browning of white adipose has the advantage of decreasing insulin resistance. We aim to identify critical differentially expressed genes (DEGs) in white adipose tissue after exercise. We downloaded the gene dataset GSE68161 of C57BL/6 mice from the Gene Expression Omnibus (GEO) database. Then, we analyzed the effect of exercise on up-regulated and down-regulated DEGs by GEO2R and performed protein-protein interaction network analyses. We then identified hub-genes in white adipose tissue and crosstalk genes of a single pathway by the STRING database and Cytoscape. In this study, 72 DEGs were screened out, and they mainly function in glycerol-3-phosphate dehydrogenase activity and in the primary biological process of fatty acid oxidation regulation. The top 5 hub-genes screened out were SLC27A1, COX7A1, PPARGC1A, FABP3, and UCP1. The 3 crosstalk genes found were SLC27A1, SLC27A2, and PPARA. These 3 genes might function as a bridge of the PPAR signaling pathway, adipocytokine signaling pathway and the insulin resistance pathway. SLC27A1 is critical gene for the interactions of signaling pathways in subcutaneous white adipose tissue. Therefore, further relationships between the browning of white adipose and insulin resistance need to be studied.

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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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Lyophilized Maqui (Aristotelia chilensis) Berry Induces Browning in the Subcutaneous White Adipose Tissue and Ameliorates the Insulin Resistance in High Fat Diet-Induced Obese Mice

Antioxidants ◽

10.3390/antiox8090360 ◽

2019 ◽

Vol 8 (9) ◽

pp. 360 ◽

Cited By ~ 6

Author(s):

Viviana Sandoval ◽

Antoni Femenias ◽

Úrsula Martínez-Garza ◽

Hèctor Sanz-Lamora ◽

Juan Castagnini ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

White Adipose Tissue ◽

High Fat Diet ◽

Binding Protein ◽

Fibroblast Growth Factor 21 ◽

Obese Mice ◽

High Fat ◽

Subcutaneous White Adipose Tissue ◽

Aristotelia Chilensis

Maqui (Aristotelia Chilensis) berry features a unique profile of anthocyanidins that includes high amounts of delphinidin-3-O-sambubioside-5-O-glucoside and delphinidin-3-O-sambubioside and has shown positive effects on fasting glucose and insulin levels in humans and murine models of type 2 diabetes and obesity. The molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance was investigated in high fat diet-induced obese mice supplemented with a lyophilized maqui berry. Maqui-dietary supplemented animals showed better insulin response and decreased weight gain but also a differential expression of genes involved in de novo lipogenesis, fatty acid oxidation, multilocular lipid droplet formation and thermogenesis in subcutaneous white adipose tissue (scWAT). These changes correlated with an increased expression of the carbohydrate response element binding protein b (Chrebpb), the sterol regulatory binding protein 1c (Srebp1c) and Cellular repressor of adenovirus early region 1A–stimulated genes 1 (Creg1) and an improvement in the fibroblast growth factor 21 (FGF21) signaling. Our evidence suggests that maqui dietary supplementation activates the induction of fuel storage and thermogenesis characteristic of a brown-like phenotype in scWAT and counteracts the unhealthy metabolic impact of an HFD. This induction constitutes a putative strategy to prevent/treat diet-induced obesity and its associated comorbidities.

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Alteration of PEPCK‐C gene expression in liver and white adipose tissue results in insulin resistance

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.856.20 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Colleen Marie Croniger ◽

David DeSantis ◽

Chang‐Wen Hsieh ◽

Carrie A Millward

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

White Adipose Tissue

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Allium hookeri Root Extract Inhibits Adipogenesis by Promoting Lipolysis in High Fat Diet-Induced Obese Mice

Nutrients ◽

10.3390/nu11102262 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2262 ◽

Cited By ~ 2

Author(s):

Kim ◽

Jang ◽

Lee

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Fatty Acid ◽

White Adipose Tissue ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Tissue Weight ◽

Adipose Tissue Weight ◽

Allium Hookeri

: Allium hookeri (AH) is widely consumed as a herbal medicine. It possesses biological activity against metabolic diseases. The objective of this study was to investigate effects of AH root water extract (AHR) on adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice. AHR inhibited lipid accumulation during adipocyte differentiation by downregulation of gene expression, such as hormone sensitive lipase (HSL), lipoprotein lipase (LPL) and an adipogenic gene, CCAAT/enhancer binding protein-α in 3T3-L1 preadipocytes. Oral administration of AHR significantly suppressed body weight gain, adipose tissue weight, serum leptin levels, and adipocyte cell size in HFD-induced obese mice. Moreover, AHR significantly decreased hepatic mRNA expression levels of cholesterol synthesis genes, such as 3-hydroxy-3-methylglutaryl CoA reductase, sterol regulatory element-binding transcription factor (SREBP)-2, and low-density lipoprotein receptor, as well as fatty acid synthesis genes, such as SREBP-1c and fatty acid synthase. Serum triglyceride levels were also lowered by AHR, likely as a result of the upregulating gene involved in fatty acid β-oxidation, carnitine palmitoyltransferase 1a, in the liver. AHR treatment activated gene expression of peroxisome proliferator-activated receptor-γ, which might have promoted HSL and LPL-medicated lipolysis, thereby reducing white adipose tissue weight. In conclusion, AHR treatment can improve metabolic alterations induced by HFD in mice by modifying expression levels of genes involved in adipogenesis, lipogenesis, and lipolysis in the white adipose tissue and liver.

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