Title:
|
Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice
|
Author:
|
Tom, Robby Zachariah; García-Roves, Pablo M. (Pablo Miguel); Sjögren, Rasmus J.O.; Jiang, Lake Q.; Holmström, Maria H.; Deshmukh, Atul S.; Vieira, Elaine; Chibalin, Alexander V.; Björnholm, Marie; Zierath, Juleen R.
|
Other authors:
|
Universitat de Barcelona |
Abstract:
|
AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the γ3 subunit (AMPKγ3(R225Q)) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKγ3(R225Q) (γ3(R225Q)) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKγ3(R225Q) prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-γ3(R225Q)) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-γ3(R225Q) mice, whereas glucose tolerance was unaltered. Insulin-stimulated glucose uptake in extensor digitorum longus muscle during the euglycemic-hyperinsulinemic clamp was increased in lean γ3(R225Q) mice, but not in ob/ob-γ3(R225Q) mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from γ3(R225Q) mutant mice independent of adiposity. Glycogen and triglyceride content were decreased after leptin treatment (5 days) in ob/ob mice, but not in ob/ob-γ3(R225Q) mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKγ3(R225Q) are insufficient to ameliorate insulin resistance and obesity in leptin-deficient mice. Central defects due to leptin deficiency may override any metabolic benefit conferred by peripheral overexpression of the AMPKγ3(R225Q) mutation. |
Subject(s):
|
-Metabolisme -Resistència a la insulina -Fisiologia -Leptina -Genètica -Músculs -Esquelet -Obesitat -Ratolins (Animals de laboratori) -Metabolism -Insulin resistance -Physiology -Leptin -Genetics -Muscles -Skeleton -Obesity -Mice (Laboratory animals) |
Rights:
|
cc-by-nc-nd (c) American Diabetes Association, 2014
http://creativecommons.org/licenses/by-nc-nd/3.0/es |
Document type:
|
Article Article - Published version |
Published by:
|
American Diabetes Association
|
Share:
|
|