[Role of Angiogenesis and Chronic Inflammation in Fat Hypertrophy in NASH Pathology].

[Role of Angiogenesis and Chronic Inflammation in Fat Hypertrophy in NASH Pathology]. Yakugaku Zasshi. 2019;139(9):1163-1167 Authors: Wada T, Tsuneki H, Sasaoka T Abstract Tissue expansion and chronic inflammation in adipose tissue (AT) are closely related to nonalcoholic steatohepatitis (NASH) pathology. Angiogenesis is initiated by the detachment of pericytes (PCs) from vessels in AT. This process is necessary for the development of AT in obesity. The detachment is caused by excessive platelet-derived growth factor B (PDGF-B) derived from M1-macrophages (Mφ) infiltrating obese AT. On the other hand, AT of tamoxifen-induced systemic PDGF receptor-β knockout mice showed decreased detachment of PCs from vessels in obesity, thereby attenuating hypertrophy of AT mediated by neoangiogenesis, resulting in protection from the development of chronic AT inflammation and systemic insulin resistance. The selective mineralocorticoid receptor (MR) inhibitor eplerenone (Ep) suppresses chronic inflammation in fat and the liver, improves glucose and lipid metabolism, and inhibits body weight and fat mass gain in mice fed a high-fat diet. As a novel mechanism, Ep increases energy expenditure and suppresses fat accumulation, thereby controlling the polarity of visceral AT Mφ from inflammatory M1 to anti-inflammatory M2 dominant. In addition, Ep directly inhibits the activation of signals 1 and 2 of NLRP3-inflammasomes in Mφ, which is an inflammat...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research