Acetate rescues defective brain-adipose metabolic network in obese Wistar rats by modulation of peroxisome proliferator-activated receptor-γ.

We investigated the hypothesis that acetate ameliorates brain-adipose metabolic dysfunction (BAMED) in high fat diet (HFD)-induced obesity, possibly by modulation of peroxisome proliferator-activated receptor-γ (PPAR-γ). Ten-week-old male Wistar rats were randomly assigned into four groups (n = 6/group): Control, acetate and obese with or without acetate groups received vehicle (distilled water; po), acetate (200 mg/kg, po) and 40% HFD with or without acetate respectively. The treatments lasted for 12 weeks. Obese animals showed increase in body weight, visceral fat mass, insulin and triglyceride-glucose index and a reduction in insulin sensitivity. In addition, obese animals also showed increase in plasma/hypothalamic and adipose pyruvate dehydrogenase kinase-4, lactate-pyruvate ratio, malondialdehyde, γ-glutamyl transferase, and a decrease in glucose-6-phosphate dehydrogenase, glutathione, nitric oxide and PPAR-γ. HFD also elevated plasma/hypothalamic lipid and decreased adipose lipid profile, increased hypothalamic and adipose tumor necrosis factor-α, interleukin-6 and histone deacetylase (HDAC), and elevated plasma/adipose leptin. These alterations were reversed by concomitant administration of acetate. The present results demonstrate that obesity is characterized by BAMED, which is accompanied by altered HDAC/PPAR-γ. The results in addition suggest that acetate, an HDAC inhibitor rescues BAMED with consequent normalization of body weight and visceral fat mass by modulation of PPAR-γ and suppression of oxidative stress.