Metabolism of sex steroids is influenced by acquired adiposity-A study of young adult male monozygotic twin pairs.
Level 4 - case-series / case-control
cross-sectional discordant monozygotic twin study
PubMed 28619249 · doi:10.1016/j.jsbmb.2017.06.007
What was done
Researchers evaluated the associations between adiposity, sex hormone concentrations, and subcutaneous adipose tissue gene expression independent of age and genetics in 18 young adult male monozygotic twin pairs (mean age 32 years, BMI range 22–36 kg/m²), including 9 pairs discordant for BMI (intra-pair difference ≥3 kg/m²). Serum sex steroids were measured using liquid chromatography-tandem mass spectrometry, body composition was assessed by DXA and MRI, and mRNA expression in subcutaneous adipose tissue was measured by Affymetrix microarrays.
What was found
In BMI-discordant pairs (mean BMI difference 5.9 kg/m²), heavier co-twins had lower serum dihydrotestosterone (DHT) (mean 1.9 [SD 0.7] vs. 2.4 [1.0] nmol/l, P=0.040) and higher free 17β-estradiol (E2) (2.3 [0.5] vs. 1.9 [0.5] pmol/l, P=0.028) compared to leaner co-twins. Subcutaneous adipose mRNA expressions of DHT-inactivating AKR1C2 (P=0.021) and cortisol-producing HSD11B1 (P=0.008) were higher in heavier co-twins. Across all 18 pairs, heavier twins had higher serum E2 (107 [28] vs. 90 [22] pmol/l, P=0.006) and estrone (123 [43] vs. 105 [27] pmol/l, P=0.025). Subcutaneous fat inversely correlated with total testosterone, free testosterone, DHT, and SHBG (P<0.01 for all); intra-abdominal fat inversely correlated with total testosterone and SHBG (P<0.05); and liver fat inversely correlated with SHBG (P=0.006). Adiposity correlated positively with adipose mRNA expression of AKR1C2, HSD11B1, and aromatase (P<0.05).
Why it matters
Controlling for genetic background and age via a monozygotic twin design demonstrates that acquired fat mass directly shifts sex steroid balance toward lower active androgens and higher estrogens, likely mediated by altered steroid-metabolizing enzyme expression in adipose tissue.
Limits
The study is limited by a small sample size (18 twin pairs, with only 9 BMI-discordant pairs). The cross-sectional design cannot confirm causal directionality. Adipose tissue biopsy was restricted to subcutaneous fat, leaving intra-abdominal fat gene expression unmeasured. All subjects were young adult men, limiting generalizability to older men or females.
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