Impact of Sodium Butyrate Supplementation on Insulin Resistance and Adipose Tissue Modulation in Murine Models of Polycystic Ovary Syndrome.

OBJECTIVES

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder affecting up to 10% of women of reproductive age, commonly associated with visceral obesity, insulin resistance, and chronic low-grade inflammation. Sodium butyrate, a microbial-derived short-chain fatty acid, has been proposed as a therapeutic agent due to its anti-inflammatory and metabolic regulatory properties. However, its efficacy under hyperandrogenic and pro-inflammatory conditions remains uncertain.

DESIGN

Experimental study using prepubertal female BALB/c mice (n = 40) allocated into five groups: control (CT), high-fat diet (HFD), DHEA (HFD + dehydroepiandrosterone), BUT (HFD + sodium butyrate), and DHEA+BUT (HFD + DHEA + sodium butyrate).

PARTICIPANTS/MATERIALS, SETTING,

METHODS

Hyperandrogenism was induced by subcutaneous DHEA implants, and obesity by a high-fat diet (60% kcal from fat). Sodium butyrate (100 mg/kg/day) was administered by oral gavage during the last 40 days of the 90-day protocol. This five-group design allowed the evaluation of butyrate effects in obesity alone (BUT) and in the combined obese-hyperandrogenic state (DHEA + BUT). Body weight, glucose tolerance, adipose depot weights, gene expression (IL-6, TNF-α, UCP1), serum adipokines.

RESULTS

Butyrate-treated groups, particularly DHEA + BUT, exhibited greater body weight gain and adipose tissue expansion than controls (p < 0.01). Glucose tolerance tests revealed impaired glycemic control in all HFD-fed groups, with the BUT group showing the highest peaks (p < 0.05). IL-6 and TNF-α expression were upregulated in visceral adipose tissue of butyrate-treated animals, while adiponectin levels were reduced in DHEA + BUT.

LIMITATIONS: The modest number of animals per group reduced statistical power, reflecting constraints in breeding and availability of age-matched BALB/c mice. Their relatively small adipose depots limited tissue yield for molecular and histological assays. Daily oral gavage, required for precise dosing, was technically challenging and led to the loss of one DHEA+BUT animal.

CONCLUSIONS

In this model of preestablished obesity and hyperandrogenism, sodium butyrate supplementation was not metabolically protective. Instead, it exacerbated adipose inflammation, altered adipokine profiles, and impaired glucose regulation. These findings underscore the context-dependent nature of butyrate's effects and suggest caution in extrapolating its benefits to hyperandrogenic or obesity-associated PCOS phenotypes.