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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 effects are independent of changes in gastrocnemius muscle redox state.Effects of one-month high-fat feeding without (HF) or with (HFG) 4-day acylated ghrelin treatment on plasma TBARS concentration (a) and on gastrocnemius muscle glutathione peroxidase activity (b), and total 1 oxidized glutathione  ratio (c). Different letters denote statistically significant differences (P<0.05 ANOVA and post-hoc test).
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pone-0026224-g003: Acylated ghrelin effects are independent of changes in gastrocnemius muscle redox state.Effects of one-month high-fat feeding without (HF) or with (HFG) 4-day acylated ghrelin treatment on plasma TBARS concentration (a) and on gastrocnemius muscle glutathione peroxidase activity (b), and total 1 oxidized glutathione ratio (c). Different letters denote statistically significant differences (P<0.05 ANOVA and post-hoc test).

Mentions: A-Ghr treatment lead to lower levels of nuclear p65 NFkB and tissue TNF-alpha in skeletal muscle compared to both HF and C (Figure 1a–b). Mitochondrial enzyme activities were conversely higher in HFG than in control and HF animals, although this difference only reached statistical significance between HFG and control values (Figure 2a–b). Under the above conditions, ghrelin treatment was associated with normalization of the high-fat diet-induced skeletal muscle triglyceride accumulation (Figure 2c).


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 effects are independent of changes in gastrocnemius muscle redox state.Effects of one-month high-fat feeding without (HF) or with (HFG) 4-day acylated ghrelin treatment on plasma TBARS concentration (a) and on gastrocnemius muscle glutathione peroxidase activity (b), and total 1 oxidized glutathione  ratio (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-g003: Acylated ghrelin effects are independent of changes in gastrocnemius muscle redox state.Effects of one-month high-fat feeding without (HF) or with (HFG) 4-day acylated ghrelin treatment on plasma TBARS concentration (a) and on gastrocnemius muscle glutathione peroxidase activity (b), and total 1 oxidized glutathione ratio (c). Different letters denote statistically significant differences (P<0.05 ANOVA and post-hoc test).
Mentions: A-Ghr treatment lead to lower levels of nuclear p65 NFkB and tissue TNF-alpha in skeletal muscle compared to both HF and C (Figure 1a–b). Mitochondrial enzyme activities were conversely higher in HFG than in control and HF animals, although this difference only reached statistical significance between HFG and control values (Figure 2a–b). Under the above conditions, ghrelin treatment was associated with normalization of the high-fat diet-induced skeletal muscle triglyceride accumulation (Figure 2c).

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