Skeletal Muscle Nucleo-Mitochondrial Crosstalk in Obesity and Type 2 Diabetes.

Abstract

Skeletal muscle mitochondrial dysfunction, evidenced by incomplete beta oxidation and accumulation of fatty acid intermediates in the form of long and medium chain acylcarnitines, may contribute to ectopic lipid deposition and insulin resistance during high fat diet (HFD)-induced obesity. The present review discusses the roles of anterograde and retrograde communication in nucleo-mitochondrial crosstalk that determines skeletal muscle mitochondrial adaptations, specifically alterations in mitochondrial number and function in relation to obesity and insulin resistance. Special emphasis is placed on the effects of high fat diet (HFD) feeding on expression of nuclear-encoded mitochondrial genes (NEMGs) nuclear receptor factor 1 (NRF-1) and 2 (NRF-2) and peroxisome proliferator receptor gamma coactivator 1 alpha (PGC-1α) in the onset and progression of insulin resistance during obesity and how HFD-induced alterations in NEMG expression affect skeletal muscle mitochondrial adaptations in relation to beta oxidation of fatty acids. Finally, the potential ability of acylcarnitines or fatty acid intermediates resulting from mitochondrial beta oxidation to act as retrograde signals in nucleo-mitochondrial crosstalk is reviewed and discussed.

• Authors: Prasad P Devarshi, Sean M McNabney, Tara M Henagan
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 18 Issue 4 (Apr 14 2017) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 28420087 (Publication Type: Journal Article, Review)

Chemical References

• Insulin
• Glucose

Topics

• Animals
• Cell Nucleus (metabolism)
• Diabetes Mellitus, Type 2 (etiology, metabolism)
• Diet, High-Fat
• Energy Metabolism
• Evolution, Molecular
• Glucose (metabolism)
• Humans
• Insulin (metabolism)
• Insulin Resistance
• Mitochondria, Muscle (genetics, metabolism)
• Muscle, Skeletal (metabolism)
• Obesity (etiology, metabolism)
• Oxidation-Reduction
• Signal Transduction