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: 3-Isobutyl-1-methylxanthine (PubChem CID: 3758); ASC-J9 (PubChem CID: 6477182); Adipocyte differentiation; Dexamethasone (PubChem CID: 5743); Formaldehyde (PubChem CID: 712); Gαi 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).
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