Endocrine Abstracts

Background: Endocrine-metabolic disorders, especially polycystic ovarian syndrome (PCOS) has been linked with increased risk of non-alcoholic fatty liver disease (NAFLD) among reproductive age and implicated hyperandrogenism-driven adipose/hepatic insulin resistance (IR). Gut microbial metabolites such as short chain fatty acids (SCFAs) are crucial modulators of metabolic regulation. However, the impact of SCFAs, in particular, acetate on hyperandrogenism and/or adipose/hepatic IR in PCOS model is unclear. This study therefore hypothesized that acetate would break the vicious cycle that drives adipose-hepatic metabolic dysregulation in a rat model of PCOS, possibly by suppression of NF-κB/NLRP3 inflammasome.

Methods: Female Wistar rats (eight-week-old) were randomly allocated into 4 groups of n=six/group, which received vehicle, sodium acetate (200 mg), letrozole (1 mg/kg) and letrozole plus sodium acetate respectively. The animals were treated by oral gavage, once daily for a period of 21 days.

Results: The PCOS animals were insulin resistant, hyperandrogenic and hypoestrogenic with decreased SHBG. In addition, the liver had increased lipid profile and decreased glycogen synthesis, while the adipose tissue showed decreased lipid profile with elevated glycogen synthesis. Besides, the results also showed increased malondialdehyde, γ-glutamyl transferase, lactate dehydrogenase, inflammatory mediators with corresponding decrease in antioxidant system in the liver and adipose tissues. Immunohistochemical evaluation also demonstrated severe expression with BAX/NLRP3 antibodies. Nonetheless, concomitant acetate supplementation attenuated these derangements.

Conclusion: The present data collectively suggest that acetate reverses adipose-hepatic glycolipid dysregulation in experimental PCOS model by attenuating androgen excess and NF-κB/NLRP3 immunoreactivity.