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Updated: Jun 14, 2025
08:34
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
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Dysregulation of HO-1-SIRT1 Axis is Associated with AngII-Induced Adipocyte Dysfunction.
Hari Vishal Lakhani1, Mishghan Zehra1, Sneha Pillai1
1Department of Surgery, Internal Medicine, and Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, United States of America.
Journal of Clinical and Medical Sciences
|September 6, 2024
Summary
Heme Oxygenase-1 (HO-1) induction mitigates Angiotensin II (AngII) detrimental effects on adipocytes by restoring redox balance and rescuing Sirtuin-1 (SIRT1). This highlights HO-1 as a therapeutic target for metabolic dysfunction.
Area of Science:
- Metabolic Research
- Adipose Tissue Biology
- Oxidative Stress and Redox Biology
Background:
- The Renin-Angiotensin-Aldosterone System (RAAS) component Angiotensin II (AngII) is implicated in adipose tissue dysfunction.
- Oxidative stress, induced by AngII, can suppress Sirtuin-1 (SIRT1), a key regulator of cellular metabolism.
- Heme Oxygenase-1 (HO-1) is an antioxidant enzyme known to counteract oxidative stress and improve adipocyte phenotype.
Purpose of the Study:
- To investigate the mechanism by which AngII-induced oxidative stress suppresses adipocyte SIRT1 via HO-1 down-regulation.
- To determine if HO-1 induction can rescue SIRT1, improve oxidative stress, and ameliorate adipocyte dysfunction.
- To explore the role of Mineralocorticoid Receptor (MR) in AngII-mediated effects on adipocytes.
Main Methods:
- Experiments utilized mouse preadipocytes treated with AngII, the HO-1 inducer Cobalt Protoporphyrin (CoPP), and the HO-1 inhibitor Tin Mesoporphyrin (SnMP).
- Assessed lipid accumulation, superoxide levels, inflammatory cytokines (IL-6, TNF-alpha), adiponectin, MR, and SIRT1 expression.
- Investigated the role of SIRT1 using siRNA in conjunction with CoPP treatment.
Main Results:
- AngII treatment increased lipid accumulation, superoxide, and inflammatory cytokines while decreasing adiponectin in preadipocytes.
- HO-1 induction (CoPP) attenuated AngII-induced detrimental effects, which were reversed by HO-1 inhibition (SnMP).
- AngII upregulated MR and suppressed SIRT1, effects rescued by HO-1 induction; HO-1's benefits were mediated through SIRT1.
Conclusions:
- HO-1 induction effectively restores cellular redox balance and rescues SIRT1 expression in adipocytes under AngII stress.
- HO-1 activation attenuates the adverse effects of AngII on adipocyte function and systemic metabolic profile.
- Targeting HO-1 presents a promising therapeutic strategy for managing metabolic disorders associated with RAAS dysregulation.
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