Abstract
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.
Highlights
We investigated the hypothesis that acetate ameliorates brain-adipose metabolic dysfunction (BAMED) in high fat diet (HFD)-induced obesity, possibly by modulation of peroxisome proliferatoractivated receptor-γ (PPAR-γ)
Though the fasting blood glucose remained unchanged (p < 0.05) but a significant decrease in glucose tolerance and insulin sensitivity were observed in obese animals compared with control animals and these were significantly increased (p < 0.05) following the administration of acetate to OBS + ACT group compared to the untreated obese group and no significant difference when compared to the control group
There was a significant increase (p < 0.05) in fasting plasma insulin and triglyceride-glucose (TyG) ratio in obese animals compared with control animals and these were normalized following the administration of acetate to OBS + ACT group compared to the untreated obese group (Fig. 2)
Summary
We investigated the hypothesis that acetate ameliorates brain-adipose metabolic dysfunction (BAMED) in high fat diet (HFD)-induced obesity, possibly by modulation of peroxisome proliferatoractivated receptor-γ (PPAR-γ). HFD 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. Leptin is secreted by adipocytes in proportion to total fat m ass[14] and regulates energy balance by reducing energy intake or increasing energy e xpenditure[13] It reduces energy intake by decreasing food or caloric intake through appetite inhibition in the hypothalamus, thereby preventing excess body weight[15]. Hyperleptinemia could induce or aggravate leptin insensitivity by upregulating the suppressor of cytokine signalling-3 (SOCS-3) with consequent blockade of signal transduction of leptin[17,18]
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