Key result
Hematopoietic androgen receptor deficiency increases visceral and total fat mass in high-fat fed male mice.
Why the study?
Does hematopoietic androgen receptor deficiency promote visceral fat deposition and impair glucose homeostasis in male mice on a high-fat diet?
Does hematopoietic androgen receptor deficiency promote visceral fat deposition and impair glucose homeostasis in male mice on a high-fat diet?
Hematopoietic androgen receptor deficiency promotes visceral fat accumulation in male mice on a high-fat diet without impairing glucose homeostasis, suggesting a mechanism for adiposity in androgen deficiency.
Macrophage AR loss may drive fat accumulation in androgen deficiency; leaves open human translation and clinical relevance.
Androgen deficiency in men increases body fat, but the mechanisms by which testosterone suppresses fat deposition have not been elucidated fully. Adipose tissue macrophages express the androgen receptor (AR) and regulate adipose tissue remodeling. Thus, testosterone signaling in macrophages could alter the paracrine function of these cells and thereby contribute to the metabolic effects of androgens in men. A metabolic phenotyping study was performed to determine whether the loss of AR signaling in hematopoietic cells results in greater fat accumulation in male mice. C57BL/6J male mice (ages 12-14 weeks) underwent bone marrow transplant from either wild-type (WT) or AR knockout (ARKO) donors (n = 11-13 per group). Mice were fed a high-fat diet (60% fat) for 16 weeks. At baseline, 8 and 16 weeks, glucose and insulin tolerance tests were performed, and body composition was analyzed with fat-water imaging by MRI. No differences in body weight were observed between mice transplanted with WT bone marrow [WT(WTbm)] or ARKO bone marrow [WT(ARKObm)] prior to initiation of the high-fat diet. After 8 weeks of high-fat feeding, WT(ARKObm) mice exhibited significantly more visceral and total fat mass than WT(WTbm) animals. Despite this, no differences between groups were observed in glucose tolerance, insulin sensitivity, or plasma concentrations of insulin, glucose, leptin, or cholesterol, although WT(ARKObm) mice had higher plasma levels of adiponectin. Resultant data indicate that AR signaling in hematopoietic cells influences body fat distribution in male mice, and the absence of hematopoietic AR plays a permissive role in visceral fat accumulation. These findings demonstrate a metabolic role for AR signaling in marrow-derived cells and suggest a novel mechanism by which androgen deficiency in men might promote increased adiposity. The relative contributions of AR signaling in macrophages and other marrow-derived cells require further investigation.
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Rubinow et al. (2015) studied Androgen deficiency and visceral fat deposition. Bone marrow transplant from androgen receptor knockout (ARKO) donors vs. Bone marrow transplant from wild-type (WT) donors was evaluated on Visceral and total fat mass. Hematopoietic androgen receptor deficiency in male mice significantly increased visceral and total fat mass after 8 weeks of high-fat feeding compared to wild-type controls.
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