Testosterone regulates 3T3-L1 pre-adipocyte differentiation and epididymal fat accumulation in mice through modulating macrophage polarization | Health & Environmental Research Online (HERO)

HERO ID

6016228

Reference Type

Journal Article

Title

Testosterone regulates 3T3-L1 pre-adipocyte differentiation and epididymal fat accumulation in mice through modulating macrophage polarization

Author(s)

Chen, S; Fu, X; Huang, S; Liu, G; Ren, X; Yao, L; Zhang, X

Year

2017

Is Peer Reviewed?

Yes

Journal

Biochemical Pharmacology
ISSN: 0006-2952
EISSN: 1873-2968

Book Title

Biochem Pharmacol. 2017, 09 15; 140:73-88. [Biochemical pharmacology]

Language

English

Abstract

Low testosterone levels are strongly related to obesity in males. The balance between the classically M1 and alternatively M2 polarized macrophages also plays a critical role in obesity. It is not clear whether testosterone regulates macrophage polarization and then affects adipocyte differentiation. In this report, we demonstrate that testosterone strengthens interleukin (IL) -4-induced M2 polarization and inhibits lipopolysaccharide (LPS)-induced M1 polarization, but has no direct effect on adipocyte differentiation. Cellular signaling studies indicate that testosterone regulates macrophage polarization through the inhibitory regulative G-protein (Gαi) mainly, rather than via androgen receptors, and phosphorylation of Akt. Moreover, testosterone inhibits pre-adipocyte differentiation induced by M1 macrophage medium. Lowering of serum testosterone in mice by injecting a luteinizing hormone receptor (LHR) peptide increases epididymal white adipose tissue. Testosterone supplementation reverses this effect. Therefore, our findings indicate that testosterone inhibits pre-adipocyte differentiation by switching macrophages to M2 polarization through the Gαi and Akt signaling pathways.

Keywords

3T3-L1 Cells; Adipocytes, White/drug effects/immunology/metabolism/pathology; Adipogenesis/drug effects; Adiposity/drug effects; Animals; Cell Polarity/drug effects; GTP-Binding Protein alpha Subunits, Gi-Go/agonists/antagonists & inhibitors/metabolism; Gene Expression Regulation/drug effects; Hormone Replacement Therapy; Macrophages/drug effects/immunology/metabolism/pathology; Mice, Inbred C57BL; Obesity/immunology/metabolism/pathology/prevention & control; Proto-Oncogene Proteins c-akt/antagonists & inhibitors/genetics/metabolism; RAW 264.7 Cells; RNA Interference; Signal Transduction/drug effects; Specific Pathogen-Free Organisms; Testosterone/blood/pharmacology/therapeutic use; 3-Isobutyl-1-methylxanthine (PubChem CID: 3758); ASC-J9 (PubChem CID: 6477182); Adipocyte differentiation; Dexamethasone (PubChem CID: 5743); Formaldehyde (PubChem CID: 712); GÎ±i protein; Hydroxyflutamide (PubChem CID: 91649); Insulin (Bovine) (PubChem CID: 16131099); Isopropanol (PubChem CID: 3776); Lipopolysaccharide (PubChem CID:11970143); Macrophage polarization; Testosterone; Testosterone (PubChem CID: 6013); Triton X-100 (PubChem CID: 5590); 3XMK78S47O