Dysregulation of HO-1-SIRT1 Axis is Associated with AngII-Induced Adipocyte Dysfunction.

Autor:	Lakhani HV; Department of Surgery, Internal Medicine, and Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, United States of America., Zehra M; Department of Surgery, Internal Medicine, and Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, United States of America., Pillai S; Department of Surgery, Internal Medicine, and Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, United States of America., Shapiro JI; Department of Surgery, Internal Medicine, and Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, United States of America., Sodhi K; Department of Surgery, Internal Medicine, and Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, United States of America.
Jazyk:	angličtina
Zdroj:	Journal of clinical and medical sciences [J Clin Med Sci] 2024; Vol. 8 (2). Date of Electronic Publication: 2024 May 20.
Abstrakt:	Angiotensin II (AngII), a component of the Renin-Angiotensin-Aldosterone System (RAAS), has been implicated in the dysregulation of adipose tissue function. Inhibition of AngII has been shown to improve adipose tissue function in mice with metabolic syndrome. It is well established that the Heme Oxygenase-1 (HO-1), an antioxidant improves oxidative stress and phenotypic change in adipocytes. Molecular effects of high oxidative stress include suppression of Sirtuin-1 (SIRT1), which is amenable to redox manipulations. However, the underlying mechanisms by which the Renin-Angiotensin-Aldosterone System (RAAS) exerts its metabolic effects are not fully understood. In this study, we propose that AngII-induced oxidative stress may suppress adipocyte SIRT1 through down-regulation of HO-1. Consequently, this suppression of SIRT1 may result in the up-regulation of the Mineralocorticoid Receptor (MR). We further hypothesize that the induction of HO-1 would rescue SIRT1, thereby improving oxidative stress and adipocyte phenotype. To establish this hypothesis, we conducted experiments using mouse preadipocytes treated with AngII, in the presence or absence of Cobalt Protoporphyrin (CoPP), an inducer of HO-1, and Tin Mesoporphyrin (SnMP), an inhibitor of HO-1. Our data demonstrate that treatment of mouse preadipocytes with AngII leads to increased lipid accumulation, elevated levels of superoxide and inflammatory cytokines (Interleukin-6 and Tumor necrosis factor alpha), and reduced levels of adiponectin. However, these effects were attenuated by the induction of HO-1, and this attenuation was reversed by SnMP, indicating that the beneficial effects on adipocyte phenotype are modulated by HO-1. Furthermore, our findings reveal that AngII-treated preadipocytes exhibit upregulated MR levels and suppressed SIRT1 expression, which are rescued by HO-1 induction. Following treatment with CoPP and SIRT1 siRNA in mouse preadipocytes resulted in increased lipid accumulation and elevated levels of fatty acid synthase, indicating that the beneficial effects of HO-1 are modulated through SIRT1. Our study provides evidence that HO-1 restores cellular redox balance, rescues SIRT1, and attenuates the detrimental effects of AngII on adipocytes and systemic metabolic profile. Competing Interests: CONFLICT OF INTEREST The authors have declared that no competing interests exist.
Databáze:	MEDLINE
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