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Circulating sex steroids coregulate adipose tissue immune cell populations in healthy men.

ABSTRACT: Male hypogonadism results in changes in body composition characterized by increases in fat mass. Resident immune cells influence energy metabolism in adipose tissue and could promote increased adiposity through paracrine effects. We hypothesized that manipulation of circulating sex steroid levels in healthy men would alter adipose tissue immune cell populations. Subjects (n = 44 men, 19-55 yr of age) received 4 wk of treatment with the gonadotropin-releasing hormone receptor antagonist acyline with daily administration of 1) placebo gel, 2) 1.25 g testosterone gel (1.62%), 3) 5 g testosterone gel, or 4) 5 g testosterone gel with an aromatase inhibitor. Subcutaneous adipose tissue biopsies were performed at baseline and end-of-treatment, and adipose tissue immune cells, gene expression, and intra-adipose estrogen levels were quantified. Change in serum total testosterone level correlated inversely with change in the number of CD3+ (??=?-0.36, P = 0.04), CD4+ (??=?-0.34, P = 0.04), and CD8+ (??=?-0.33, P = 0.05) T cells within adipose tissue. Change in serum 17?-estradiol level correlated inversely with change in the number of adipose tissue macrophages (ATMs) (??=?-0.34, P = 0.05). A negative association also was found between change in serum testosterone and change in CD11c+ ATMs (??=?-0.41, P = 0.01). Overall, sex steroid deprivation was associated with increases in adipose tissue T cells and ATMs. No associations were found between changes in serum sex steroid levels and changes in adipose tissue gene expression. Circulating sex steroid levels may regulate adipose tissue immune cell populations. These exploratory findings highlight a possible novel mechanism that could contribute to increased metabolic risk in hypogonadal men.

SUBMITTER: Rubinow KB

PROVIDER: S-EPMC5792144 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Circulating sex steroids coregulate adipose tissue immune cell populations in healthy men.

Rubinow Katya B KB Chao Jing H JH Hagman Derek D Kratz Mario M Van Yserloo Brian B Gaikwad Nilesh W NW Amory John K JK Page Stephanie T ST

American journal of physiology. Endocrinology and metabolism 20170711 5

Male hypogonadism results in changes in body composition characterized by increases in fat mass. Resident immune cells influence energy metabolism in adipose tissue and could promote increased adiposity through paracrine effects. We hypothesized that manipulation of circulating sex steroid levels in healthy men would alter adipose tissue immune cell populations. Subjects (<i>n</i> = 44 men, 19-55 yr of age) received 4 wk of treatment with the gonadotropin-releasing hormone receptor antagonist ac ...[more]

PMID: 28698282

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Project description:IntroductionAdipokines are highly active biopeptides involved in glucose metabolism, insulin regulation and the development and progression of obesity and its associated diseases. It includes, among others, adiponectin, visfatin and tumor necrosis factor alpha (TNFα). The sources of adipokines and their associations with glucometabolic variables are not completely understood.AimIn this cross-sectional study, we aimed to investigate whether gene expression levels in subcutaneous adipose tissue (SAT) of selected adipokines and their corresponding circulating levels associate with the amount of AT in superficial (sSAT), deep (dSAT) and visceral AT (VAT), assessed by computed tomography (CT). Any association with glucometabolic variables were also explored.MethodsIn 103 healthy Caucasian men, aged 39.5 years, fasting venous blood and SAT samples from the gluteal region were collected. Ninety-four of the participants underwent CT assessment of the abdominal AT, which was divided into VAT, sSAT and dSAT. Circulating levels of adipokines were measured by ELISA and AT gene-expression by PCR. Insulin sensitivity was determined by glucose clamp, assessing glucose disposal rate (GDR).ResultsCirculating adiponectin and TNFα gene expression correlated inversely and positively to the amount of AT in all three compartments (r=-0.266 to -0.276, p<0.05 for all) and (r=0.323 - 0.368, p<0.05 for all), respectively, with strongest correlations to the amount in sSAT and dSAT. When dividing AT compartments into quartiles, a tendency was observed towards lower circulating adiponectin and higher TNFα gene expression levels, respectively, with increasing amount of sSAT and dSAT. Circulating adiponectin correlated inversely to insulin, C-peptide and waist circumference (r=-456 to -0.373, p<0.001) and positively to GDR (r=0.356, p<0.001). AT-expressed visfatin correlated inversely to insulin and C-peptide (r=-0.370 and r=-0.404, p<0.001).ConclusionIncreased amount of AT is associated with lower levels of adiponectin and increased levels of TNFα AT expression.

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Circulating sex steroids coregulate adipose tissue immune cell populations in healthy men.

Publications

Circulating sex steroids coregulate adipose tissue immune cell populations in healthy men.

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