Increased adipose tissue indices of androgen catabolism and aromatization in women with metabolic dysfunction

Giada Ostinelli , Sofia Laforest, Scott G. Denham, Marie-Frederique Gauthier, Drolet-Labelle Virginie, Emma Scott, Frédéric-Simon Hould, Simon Marceau, Natalie Z M Homer, Catherine Bégin , Ruth Andrew, André Tchernof

Research output: Contribution to journalArticlepeer-review


Body fat distribution is a risk factor for obesity-associated comorbidities, and adipose tissue dysfunction plays a role in this association. In humans, there is a sex difference in body fat distribution, and steroid hormones are known to regulate several cellular processes within adipose tissue. Our aim was to investigate if intra-adipose steroid concentration and expression or activity of steroidogenic enzymes were associated with features of adipose tissue dysfunction in individuals with severe obesity.

Samples from 40 bariatric candidates (31 women, 9 men) were included in the study. Visceral (VAT) and subcutaneous adipose tissue (SAT) were collected during surgery. Adipose tissue morphology was measured by a combination of histological staining and semi-automated quantification. Following extraction, intra-adipose and plasma steroid concentrations were determined by liquid chromatography, electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Aromatase activity was estimated using product-over-substrate ratio, while AKR1C2 activity was measured directly by fluorogenic probe. Gene expression was measured by quantitative PCR.

VAT aromatase activity was positively associated with VAT adipocyte hypertrophy (p-valueadj < 0.01) and negatively with plasma HDL-cholesterol (p-valueadj < 0.01), while SAT aromatase activity predicted dyslipidemia in women even after adjustment for waist circumference, age and hormonal contraceptive use. We additionally compared women with high and low visceral adiposity index (VAI) and found that VAT excess is characterized by adipose tissue dysfunction, increased androgen catabolism mirrored by increased AKR1C2 activity and higher aromatase expression and activity indices.

In women, increased androgen catabolism or aromatization is associated with visceral adiposity and adipose tissue dysfunction.
Original languageEnglish
JournalThe Journal of Clinical Endocrinology & Metabolism (JCEM)
Publication statusPublished - 3 May 2022


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