High-fat diet with acyl-ghrelin treatment leads to weight gain with low inflammation, high oxidative capacity and normal triglycerides in rat muscle

• Published in: PloS one Vol. 6; no. 10; p. e26224
• Main Authors: Barazzoni, Rocco, Zanetti, Michela, Semolic, Annamaria, Cattin, Maria Rosa, Pirulli, Alessia, Cattin, Luigi, Guarnieri, Gianfranco
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19-10-2011; Public Library of Science (PLoS)
• Subjects: Accumulation; AKT protein; Animal models; Animals; Antioxidants; Biology; Body weight; Body weight gain; Cytokines; Cytotoxicity; Diabetes; Diet; Dietary Fats - administration & dosage; Endocrinology; Enzymes; Fatty acids; Feeding; Ghrelin; Ghrelin - pharmacology; Ghrelin - therapeutic use; Glucose; Glutathione; Glutathione peroxidase; Glutathione Peroxidase - metabolism; Growth hormones; Health sciences; High fat diet; Inflammation; Inflammation - prevention & control; Insulin; Insulin resistance; Lipids; Male; Medicine; Metabolism; Mitochondria; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Musculoskeletal system; NF-κB protein; Obesity; Oils & fats; Oxidative Stress; Pathogenesis; Peroxidase; Phosphorylation; Plasma; Rats; Rats, Wistar; Redox properties; Respiration; Rodents; Signaling; Skeletal muscle; Systems analysis; Thiobarbituric Acid Reactive Substances - metabolism; Triglycerides; Triglycerides - metabolism; Tumor necrosis factor-α; Weight Gain - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0026224

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.