Kim, Won Jun Lee, Woojung Jung, Yujung Jang, Hyuk-Jai Kim, Yong Kee Kim, Su-Nam 2024-01-19T20:31:51Z 2024-01-19T20:31:51Z 2021-09-02 2019-03-19 0006-291X https://pubs.kist.re.kr/handle/201004/120202 Previous reports have shown that PPAR beta/delta agonists ameliorate insulin resistance associated with type 2 diabetes mellitus (T2DM). To determine the role of PPAR beta/delta in tumor necrosis factor alpha (TNF alpha)-mediated insulin resistance, we investigated expression levels of adiponectin and insulin receptor (IR) in response to treatment with the PPAR beta/delta agonist GW501516 with or without TNF alpha, a proinflammatory cytokine, in differentiated 3T3-L1 adipocytes. GW501516 induced adipocyte differentiation and the expression of adiponectin in a dose-dependent manner in differentiated adipocytes. TNF alpha treatment reduced adiponectin expression at the end of differentiation. This effect was reversed by GW501516 co-treatment with TNF alpha. TNF alpha treatment decreased adipogenic marker genes such as PPAR gamma, aP2, resistin, and GLUT4, and GW501516 reversed the effects of TNF alpha. GW501516 treatment increased the expression of insulin receptor and inhibited TNF alpha-mediated repression of insulin receptor. Our results showed that GW501516 abrogated TNF alpha-induced insulin resistance. In summary, our study demonstrated that the PPAR beta/delta agonist, GW501516 reversed TNF alpha-induced decreases in adipocyte differentiation and adiponectin expression, and improved insulin sensitivity by increasing the expression of insulin receptor. Therefore, PPAR delta may be a promising therapeutic target for treatment of insulin resistance in patients with T2DM. (C) 2019 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE NECROSIS-FACTOR-ALPHA LIPID-METABOLISM ADIPOSE-TISSUE EXPRESSION RESISTANCE ACTIVATION FAT GLUCOSE OBESITY PPAR beta/delta agonist GW501516 inhibits TNF alpha-induced repression of adiponectin and insulin receptor in 3T3-L1 adipocytes Article 10.1016/j.bbrc.2019.02.013 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.510, no.4, pp.621 - 628 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 510 4 621 628 scie scopus 000460188400021 2-s2.0-85061162300 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article NECROSIS-FACTOR-ALPHA LIPID-METABOLISM ADIPOSE-TISSUE EXPRESSION RESISTANCE ACTIVATION FAT GLUCOSE OBESITY PPAR beta/delta agonist GW501516 TNF alpha Adiponectin Insulin receptor