GW0742 (PPAR-beta agonist) attenuates hepatic endoplasmic reticulum stress by improving hepatic energy metabolism in high-fat diet fed mice. (15th October 2018)

• Record Type: Journal Article
• Authors: Silva-Veiga, Flavia Maria; Rachid, Tamiris Lima; de Oliveira, Letícia; Graus-Nunes, Francielle; Mandarim-de-Lacerda, Carlos Alberto; Souza-Mello, Vanessa
• Is Part Of: Molecular and cellular endocrinology. Volume 474(2018)
• Page Start: 227
• Page End: 237
• Publication Date: 2018-10-15
• Subjects: PPAR-beta -- Obesity -- Lipogenesis -- Beta-oxidation -- NAFLD -- ER stress; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.03.013
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Endoplasmic reticulum (ER) stress and hepatic steatosis are intertwined with insulin resistance. PPARs are at the crossroads of these pathways. This study aimed to investigate the effects of GW0742 (PPAR-beta agonist) on hepatic energy metabolism and ER stress in a murine diet-induced obesity model. HF diet caused overweight, hyperinsulinemia, hepatic inflammation (increased NF-kB, TNF-alpha, and IL-6 protein expression) and favored hepatic lipogenesis, leading to ER stress, with ultrastructural and molecular alterations, ending up in proapoptotic stimulus. GW0742 rescued the overweight and the glucose tolerance, tackled hepatic inflammation and favored hepatic beta-oxidation over lipogenesis. These results comply with ER ultrastructure improvement, reducing ER stress and apoptosis in treated animals. Our results indicate that the PPAR-beta/delta activation alleviated the ER stress by improving the insulin sensitivity and maximizing the hepatic energy metabolism with a shift towards beta-oxidation. PPAR-beta/delta activation could be an essential tool to avoid the NAFLD progression and other obesity constraints. Highlights: Endoplasmic reticulum (ER) stress is intertwined with insulin resistance and obesity. The activation of PPAR-β ameliorated hepatic steatosis and insulin resistance. PPAR-β activation alleviated ER stress and countered hepatic lipogenesis. Increased beta-oxidation and reduced inflammation and apoptosis mediated the findings. PPAR-β is a promising target to hepatic ultrastructural enhancement in obesity.