title: High-fat diet with acyl-ghrelin treatment leads to weight gain with low inflammation, high oxidative capacity and normal triglycerides in rat muscle.
abstract: Obesity is associated with muscle lipid accumulation. Experimental models suggest that inflammatory cytokines, low mitochondrial oxidative capacity and paradoxically high insulin signaling activation favor this alteration. The gastric orexigenic hormone acylated ghrelin (A-Ghr) has antiinflammatory effects in vitro and it lowers muscle triglycerides while modulating mitochondrial oxidative capacity in lean rodents. We tested the hypothesis that A-Ghr treatment in high-fat feeding results in a model of weight gain characterized by low muscle inflammation and triglycerides with high muscle mitochondrial oxidative capacity. A-Ghr at a non-orexigenic dose (HFG: twice-daily 200-µg s.c.) or saline (HF) were administered for 4 days to rats fed a high-fat diet for one month. Compared to lean control (C) HF had higher body weight and plasma free fatty acids (FFA), and HFG partially prevented FFA elevation (P<0.05). HFG also had the lowest muscle inflammation (nuclear NFkB, tissue TNF-alpha) with mitochondrial enzyme activities higher than C (P<0.05 vs C, P = NS vs HF). Under these conditions HFG prevented the HF-associated muscle triglyceride accumulation (P<0.05). The above effects were independent of changes in redox state (total-oxidized glutathione, glutathione peroxidase activity) and were not associated with changes in phosphorylation of AKT and selected AKT targets. Ghrelin administration following high-fat feeding results in a novel model of weight gain with low inflammation, high mitochondrial enzyme activities and normalized triglycerides in skeletal muscle. These effects are independent of changes in tissue redox state and insulin signaling, and they suggest a potential positive metabolic impact of ghrelin in fat-induced obesity.
authors: Clinica Medica-Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy. barazzon@units.it
authors: Rocco
authors: R
authors: Barazzoni
authors: Michela
authors: M
authors: Zanetti
authors: Annamaria
authors: A
authors: Semolic
authors: Maria Rosa
authors: MR
authors: Cattin
authors: Alessia
authors: A
authors: Pirulli
authors: Luigi
authors: L
authors: Cattin
authors: Gianfranco
authors: G
authors: Guarnieri
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D054439:Ghrelin / Q000494:pharmacology / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D004041:Dietary Fats; D054439:Ghrelin; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D005979:Glutathione Peroxidase