Invited Talk ESA-SRB-ANZOS 2025 in conjunction with ENSA

Inhibin deficiency promotes adiposity in female mice (129537)

Adam Hagg 1 , Shreya Maskey 1 2 , Nikita Fiederlein 1 , Hugo Herron-Vellacott 1 , Eliza O'Shea 1 , Luisina Ongaro 3 , Monica Goney 2 , Jennifer Outwaite 1 , Daniel J Bernard 3 4 , Craig A Harrison 2 , Kelly L Walton 1 2
  1. School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia
  2. Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  3. Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada
  4. Department of Anatomy and Cell Biology, McGill University, Montreal, Canada

Ovarian inhibins, members of the transforming growth factor – beta superfamily, are classically known for their abilities to constrain follicle stimulating hormone (FSH) production at the pituitary. Roles for inhibins beyond the pituitary are poorly understood owing to knockout models developing pathological increases in activins, triggering gonadal tumour growth and lethal body wasting. We recently generated InhaR233A/R233A mice which produce bioinactive inhibin, but importantly, do not display pathological increases in circulating activin concentrations. Adult female InhaR233A/R233A mice display a 2-3 fold elevation in serum FSH concentrations and a consequent enhancement in ovulation rates. Interestingly, compared to wildtype controls, female InhaR233A/R233A mice display exacerbated body weight increase in response to high fat diet feeding, independent of food intake. Increased body mass was attributed to hypertrophy of white adipocytes and associated with changes in cellular lipolysis. Further investigations have studied the actions of unopposed activin signalling on adipose tissue and the contributions of sex hormones to the phenotype. We report the first evidence to suggest that loss of inhibin function may alter adiposity specifically in females. Significantly, these findings may suggest that inhibin withdrawal associated with ovarian inactivation in women may contribute to adiposity.