RRC ID 58394
Author Harada N, Hanada K, Minami Y, Kitakaze T, Ogata Y, Tokumoto H, Sato T, Kato S, Inui H, Yamaji R.
Title Role of gut microbiota in sex- and diet-dependent metabolic disorders that lead to early mortality of androgen receptor-deficient male mice.
Journal Am J Physiol Endocrinol Metab
Abstract The gut microbiota is involved in metabolic disorders induced by androgen deficiency after sexual maturation in males (late-onset hypogonadism). However, its role in the energy metabolism of congenital androgen deficiency (e.g., androgen-insensitive syndrome) remains elusive. Here, we examined the link between the gut microbiota and metabolic disease symptoms in androgen receptor knockout (ARKO) mouse by administering high-fat diet (HFD) and/or antibiotics. HFD-fed male, but not standard diet-fed male or HFD-fed female, ARKO mice exhibited increased feed efficiency, obesity with increased visceral adipocyte mass and hypertrophy, hepatic steatosis, glucose intolerance, insulin resistance, and loss of thigh muscle. In contrast, subcutaneous fat mass accumulated in ARKO mice irrespective of the diet and sex. Notably, all HFD-dependent metabolic disorders observed in ARKO males were abolished after antibiotics administration. The ratios of fecal weight-to-food weight and cecum weight-to-body weight were specifically reduced by ARKO in HFD-fed males. 16S rRNA sequencing of fecal microbiota from HFD-fed male mice revealed differences in microbiota composition between control and ARKO mice. Several genera or species (e.g., Turicibacter and Lactobacillus reuteri, respectively) were enriched in ARKO mice, and antibiotics treatment spoiled the changes. Furthermore, the life span of HFD-fed ARKO males was shorter than that of control mice, indicating that androgen deficiency causes metabolic dysfunctions leading to early death. These findings also suggest that AR signaling plays a role in the prevention of metabolic dysfunctions, presumably by influencing the gut microbiome, and improve our understanding of health consequences in subjects with hypogonadism and androgen insensitivity.
Volume 318(4)
Pages E525-E537
Published 2020-4-1
DOI 10.1152/ajpendo.00461.2019
PMID 32017595
MeSH Adipocytes Adipose Tissue / pathology Animals Anti-Bacterial Agents / pharmacology Diet / adverse effects Diet, High-Fat Feces / microbiology Female Gastrointestinal Microbiome* / drug effects Lipid Metabolism Longevity Male Metabolic Diseases / microbiology* Metabolic Diseases / mortality* Metabolic Diseases / pathology Mice Mice, Inbred C57BL Mice, Knockout Obesity Receptors, Androgen / deficiency* Receptors, Androgen / genetics* Sex Characteristics
IF 3.469
Times Cited 0
Mice RBRC01828