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Intraperitoneal administration of follistatin promotes adipocyte browning in high-fat diet-induced obese mice.

ABSTRACT: With rapid economic development, the prevalence of obesity has increased remarkably worldwide. Obesity can induce a variety of metabolic diseases, such as atherosclerosis, diabetes, hypertension and coronary heart disease, which significantly endanger the health and welfare of individuals. Brown and beige fat tissues play an important role in thermogenesis in mammals. Recent studies have shown that follistatin (FST) can potentially induce the browning of white adipose tissue (WAT). In this study, high-fat diet-induced obese mice were injected with follistatin for one week to explore the effects of follistatin on browning and metabolism and to determine the mechanism. The results showed that follistatin suppressed obesity caused by a high-fat diet and increased insulin sensitivity, energy expenditure, and subcutaneous fat browning. The beneficial effects remained even after a period of withdrawal. Follistatin promoted secretion of irisin from subcutaneous fat via the AMPK-PGC1?-irisin signal pathway, which induces browning of WAT, and activated the insulin pathway in beige fat thereby promoting metabolism.

SUBMITTER: Li H

PROVIDER: S-EPMC6668797 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Intraperitoneal administration of follistatin promotes adipocyte browning in high-fat diet-induced obese mice.

Li Haoyu H Zhang Chuanhai C Liu Junyu J Xie Wenya W Xu Wentao W Liang Fei F Huang Kunlun K He Xiaoyun X

PloS one 20190731 7

With rapid economic development, the prevalence of obesity has increased remarkably worldwide. Obesity can induce a variety of metabolic diseases, such as atherosclerosis, diabetes, hypertension and coronary heart disease, which significantly endanger the health and welfare of individuals. Brown and beige fat tissues play an important role in thermogenesis in mammals. Recent studies have shown that follistatin (FST) can potentially induce the browning of white adipose tissue (WAT). In this study ...[more]

PMID: 31365569

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Project description:Aims/hypothesisDespite a similar fat storing function, visceral (intra-abdominal) white adipose tissue (WAT) is detrimental, whereas subcutaneous WAT is considered to protect against metabolic disease. Recent findings indicate that thermogenic genes, expressed in brown adipose tissue (BAT), can be induced primarily in subcutaneous WAT. Here, we investigate the hypothesis that the Wilms tumour gene product (WT1), which is expressed in intra-abdominal WAT but not in subcutaneous WAT and BAT, suppresses a thermogenic program in white fat cells.MethodsHeterozygous Wt1 knockout mice and their wild-type littermates were examined in terms of thermogenic and adipocyte-selective gene expression. Glucose tolerance and hepatic lipid accumulation in these mice were assessed under normal chow and high-fat diet conditions. Pre-adipocytes isolated from the stromal vascular fraction of BAT were transduced with Wt1-expressing retrovirus, induced to differentiate and analysed for the expression of thermogenic and adipocyte-selective genes.ResultsExpression of the thermogenic genes Cpt1b and Tmem26 was enhanced and transcript levels of Ucp1 were on average more than tenfold higher in epididymal WAT of heterozygous Wt1 knockout mice compared with wild-type mice. Wt1 heterozygosity reduced epididymal WAT mass, improved whole-body glucose tolerance and alleviated severe hepatic steatosis upon diet-induced obesity in mice. Retroviral expression of WT1 in brown pre-adipocytes, which lack endogenous WT1, reduced mRNA levels of Ucp1, Ppargc1a, Cidea, Prdm16 and Cpt1b upon in vitro differentiation by 60-90%. WT1 knockdown in epididymal pre-adipocytes significantly lowered Aldh1a1 and Zfp423 transcripts, two key suppressors of the thermogenic program. Conversely, Aldh1a1 and Zfp423 mRNA levels were increased approximately five- and threefold, respectively, by retroviral expression of WT1 in brown pre-adipocytes.Conclusion/interpretationWT1 functions as a white adipocyte determination factor in epididymal WAT by suppressing thermogenic genes. Reducing Wt1 expression in this and other intra-abdominal fat depots may represent a novel treatment strategy in metabolic disease.

Dataset Information

Intraperitoneal administration of follistatin promotes adipocyte browning in high-fat diet-induced obese mice.

Publications

Intraperitoneal administration of follistatin promotes adipocyte browning in high-fat diet-induced obese mice.

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