Ovarian inhibins (α/β dimers) are classically known for their abilities to constrain follicle stimulating hormone (FSH) production at the pituitary. Roles for inhibins beyond the pituitary have remained more elusive owing to a lack of appropriate preclinical models to examine inhibin physiology. To address this, our laboratory generated inhibin inactivated mice (InhaR233A/R233A), which lack inhibin bioactivity but not production. Loss of inhibin activity in adult female mice leads to a significant 2-3 fold elevation in serum FSH, triggering ovarian overstimulation and altered sex steroid production. Intriguingly, whilst inhibin inactivation did not alter body mass under chow diet conditions, female InhaR233A/R233Amice accumulated significantly more fat mass relative to control InhaWT/WT mice after 18-weeks on a high fat diet (HFD). We firstly aimed to characterise how inhibin inactivation in female mice led to changes in adipose tissue through histological analysis of adipocyte size. InhaR233A/R233Amice fed a HFD displayed larger adipocyte size compared to InhaWT/WT mice. Further, Western blot analysis revealed a decrease in PKA-mediated phosphorylation of hormone sensitive lipase in adipose tissue of InhaR233A/R233A mice compared to controls. Secondly, we aimed to investigate the mechanisms by which inhibin inactivity exacerbates fat accumulation in female mice. Analyses of serum hormone levels via LC-MS and steroidal hormone enzyme expression via qRT-PCR support that inhibin inactivation is associated with elevated progesterone synthesis in InhaR233A/R233Amice under HFD conditions relative to control InhaWT/WT mice. Thus, we predict that inhibin inactivation in InhaR233A/R233Amice drives fat accumulation under HFD conditions indirectly via progesterone-mediated suppression of lipolysis. Significantly, this is the first ever study to link dysregulated inhibin actions with alterations to fat.