6-Gingerol Improves Ectopic Lipid Accumulation, Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle of ageing Rats: Dual Stimulation of the AMPK/PGC-1α Signalling Pathway via Plasma Adiponectin and Muscular AdipoR1.

SCOPE: This study investigated the dual actions of 6-gingerol in stimulating both plasma adiponectin and muscular adiponectin receptor signalling in naturally ageing rats.

METHODS AND RESULTS: Twenty-two-month-old male SD rats were treated with 6-gingerol (0.2 mg/kg, once daily) for 7 weeks. 6-Gingerol could attenuate age-associated high plasma triglyceride, glucose and insulin concentrations under fasting conditions as well as suppress the increase in the HOMA-IR index and inhibit the decrease of muscular p-Akt/Akt protein in ageing rats, which indicates an improvement of systemic and muscular insulin sensitivity. Accompanying these changes, treatment with 6-gingerol attenuated excessive triglyceride accumulation, enhanced mitochondrial function, and promoted a transition from a fast- to slow-fibre type and muscle oxidative metabolism in the red gastrocnemius of ageing rats. More importantly, 6-gingerol not only increased the plasma and adipose tissue adiponectin concentrations, but also elevated muscular AdipoR1 expression and activated downstream AMPK phosphorylation as well as upregulated PGC-1α in vivo and in vitro.

CONCLUSION: 6-Gingerol may improve ectopic lipid accumulation, mitochondrial dysfunction and insulin resistance in skeletal muscle of ageing rats. These effects rely, at least in part, on the elevated plasma adiponectin concentration and muscle AdipoR1 level to dually activate the AMPK/PGC-1α signalling pathway. This article is protected by copyright. All rights reserved.