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

Barazzoni R, Zanetti M, Semolic A, Cattin MR, Pirulli A, Cattin L, Guarnieri G - PLoS ONE (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Clinica Medica-Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy. barazzon@units.it

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.

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Acylated ghrelin during HF diet does not alter AKT-dependent gastrocnemius insulin signaling.Effects of one-month high-fat feeding without (HF) or with (HFG) 4-day acylated ghrelin treatment on gastrocnemius muscle phosphorylation of AKT (a), glycogen synthase kinase (GSK) (b) and FOXO1 (c). Different letters denote statistically significant differences (P<0.05 ANOVA and post-hoc test).
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pone-0026224-g004: Acylated ghrelin during HF diet does not alter AKT-dependent gastrocnemius insulin signaling.Effects of one-month high-fat feeding without (HF) or with (HFG) 4-day acylated ghrelin treatment on gastrocnemius muscle phosphorylation of AKT (a), glycogen synthase kinase (GSK) (b) and FOXO1 (c). Different letters denote statistically significant differences (P<0.05 ANOVA and post-hoc test).

Mentions: HF had high plasma TBARS concentrations indicating high systemic lipid peroxidation. Despite this alteration, skeletal muscle redox state as reflected by the GSSG/GSH ratio was unchanged in fat-fed animals. Glutathione peroxidase is a major antioxidant enzyme and we tested the hypothesis that lack of changes in muscle redox state is associated with a stimulation of its activity in HF. A stimulation of glutathione peroxidase activity was indeed observed in HF compared to control group. HFG had similar plasma TBARS, muscle GSSG/GSH ratio and glutathione peroxidase activity compared to the HF group.


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

Barazzoni R, Zanetti M, Semolic A, Cattin MR, Pirulli A, Cattin L, Guarnieri G - PLoS ONE (2011)

Acylated ghrelin during HF diet does not alter AKT-dependent gastrocnemius insulin signaling.Effects of one-month high-fat feeding without (HF) or with (HFG) 4-day acylated ghrelin treatment on gastrocnemius muscle phosphorylation of AKT (a), glycogen synthase kinase (GSK) (b) and FOXO1 (c). Different letters denote statistically significant differences (P<0.05 ANOVA and post-hoc test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198460&req=5

pone-0026224-g004: Acylated ghrelin during HF diet does not alter AKT-dependent gastrocnemius insulin signaling.Effects of one-month high-fat feeding without (HF) or with (HFG) 4-day acylated ghrelin treatment on gastrocnemius muscle phosphorylation of AKT (a), glycogen synthase kinase (GSK) (b) and FOXO1 (c). Different letters denote statistically significant differences (P<0.05 ANOVA and post-hoc test).
Mentions: HF had high plasma TBARS concentrations indicating high systemic lipid peroxidation. Despite this alteration, skeletal muscle redox state as reflected by the GSSG/GSH ratio was unchanged in fat-fed animals. Glutathione peroxidase is a major antioxidant enzyme and we tested the hypothesis that lack of changes in muscle redox state is associated with a stimulation of its activity in HF. A stimulation of glutathione peroxidase activity was indeed observed in HF compared to control group. HFG had similar plasma TBARS, muscle GSSG/GSH ratio and glutathione peroxidase activity compared to the HF group.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Clinica Medica-Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy. barazzon@units.it

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.

Show MeSH
Related in: MedlinePlus