Unacylated Ghrelin Reduces Skeletal Muscle Reactive Oxygen Species Generation and Inflammation and Prevents High-Fat Diet-Induced Hyperglycemia and Whole-Body Insulin Resistance in Rodents

Diabetes
G Gortan CappellariR Barazzoni

Abstract

Excess reactive oxygen species (ROS) generation and inflammation may contribute to obesity-associated skeletal muscle insulin resistance. Ghrelin is a gastric hormone whose unacylated form (UnAG) is associated with whole-body insulin sensitivity in humans and may reduce oxidative stress in nonmuscle cells in vitro. We hypothesized that UnAG 1) lowers muscle ROS production and inflammation and enhances tissue insulin action in lean rats and 2) prevents muscle metabolic alterations and normalizes insulin resistance and hyperglycemia in high-fat diet (HFD)-induced obesity. In 12-week-old lean rats, UnAG (4-day, twice-daily subcutaneous 200-µg injections) reduced gastrocnemius mitochondrial ROS generation and inflammatory cytokines while enhancing AKT-dependent signaling and insulin-stimulated glucose uptake. In HFD-treated mice, chronic UnAG overexpression prevented obesity-associated hyperglycemia and whole-body insulin resistance (insulin tolerance test) as well as muscle oxidative stress, inflammation, and altered insulin signaling. In myotubes, UnAG consistently lowered mitochondrial ROS production and enhanced insulin signaling, whereas UnAG effects were prevented by small interfering RNA-mediated silencing of the autophagy m...Continue Reading

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Citations

Apr 12, 2017·International Journal of Molecular Sciences·Gustav ColldénTimo D Müller
Feb 6, 2018·Eating and Weight Disorders : EWD·Rocco BarazzoniEnzo Nisoli
Oct 26, 2018·Eating and Weight Disorders : EWD·Gianluca Gortan Cappellari, Rocco Barazzoni
Aug 6, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gianluca Gortan CappellariRocco Barazzoni
Jun 17, 2018·Scientific Reports·Chika IkenoyaIchiro Sakata
Sep 9, 2017·Endocrinology·Julie A Chowen, Jesús Argente
Jul 23, 2020·Nature Metabolism·Christina Priest, Peter Tontonoz
Sep 27, 2020·Nutrients·Dheeraj Kumar Posa, Shahid P Baba
Jan 27, 2019·International Journal of Molecular Sciences·Michela ZanettiRocco Barazzoni
Jun 23, 2020·International Journal of Endocrinology·Yonas AkaluBirhanu Ayelign
Aug 9, 2020·Reviews in Endocrine & Metabolic Disorders·Rocco Barazzoni, Gianluca Gortan Cappellari
Jul 10, 2020·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Rocco BarazzoniK Sreekumaran Nair
Jan 26, 2020·Peptides·Ming-Jie Yuan, Tao Wang
Aug 25, 2021·Journal of Neuroendocrinology·Fiona Peris-SampedroSuzanne L Dickson

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