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

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.

Diet-Related Changes of Short-Chain Fatty Acids in Blood and Feces in Obesity and Metabolic Syndrome

“…The study identification, selection, and inclusion process are summarized in Figure 2 . After eliminating duplicates, in total, 139 articles were included in this review, 112 from the first search term containing obesity [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , ...…”

“…Short-chain fatty acids consistently normalized or, in some cases, actually prevented HFD-induced alterations, such as weight gain [ 38 , 48 , 88 , 92 , 96 , 145 ], elevated insulin levels, and decreased leptin levels [ 48 , 92 , 96 , 146 ]. Consequently, SCFAs could be used in the future as a supplement to ameliorate weight gain.…”

Short chain fatty acid, acetate restores ovarian function in experimentally induced PCOS rat model

“…Blood glucose levels were monitored with a hand-held glucometer (ONETOUCH-LifeScan, Inc., Milpitas, CA, USA). Insulin sensitivity was determined using quantitative check for insulin sensitivity (QUICKI) as previously described [ 9 , 30 ].…”

“…Insulin resistance consequentially raises insulin level and prevents insulin suppression of fat lipolysis leading to peripheral lipid deposition, lipotoxicity and activated pro-oxidant/inflammatory pathways with non-adipose organs as key victims [ 7 ]. Existing evidence have shown ovarian TG accumulation and uric acid-mediated inflammation in connection with overweight in PCOS animal models [ 8 , 9 ]. Furthermore, IR-hyperinsulinemia could contribute to anovulation through stimulatory effects of luteinizing hormone (LH) on androgen production in the ovarian theca cells and via inhibition of sex hormone-binding globulin (SHBG) production by hepatocytes [ 10 ].…”

Targets of statins intervention in LDL-C metabolism: Gut microbiota

“…A Previous research revealed that oral acetate ( 58 , 59 ), propionate ( 60 ), and butyrate supplementation ( 61 , 62 ) can improve the expression of lipid metabolism genes in mice with a HFD. Examples include the upregulation of cyclic adenosine monophosphate-responsive element binding protein-regulated transcription coactivator (CRTC) 2 and phosphorylated acetyl-CoA carboxylase (p-ACC), or downregulation of peroxisome proliferator-activated receptor (PPAR) γ, acetyl-CoA carboxylase (ACC), and sterol regulatory element binding protein 1 (SREBP1) ( 63 ).…”