Obesity- and age-related alterations in FAT/CD36 translocation and lipin-1 subcellular localization in skeletal muscle of the Zucker rats

Abstract

Fatty acid (FA) uptake and/or intramuscular triglyceride (TG) accumulation in skeletal muscle are increased in obesity, type 2 diabetes and aging. FA translocase (FAT/CD36) translocation, lipin-1 subcellular localization and nuclear factor kappa B (NF-κB) p65 protein content in quadriceps muscle of young and old obese Zucker fa/fa rats and their lean controls were analyzed by immunoblot to define obesity- and aging-related alterations in FA uptake, their subsequent metabolic fate and potential to activate pro-inflammatory signaling. As expected, obesity increased FAT/CD36 content in plasma membrane in quadriceps muscle of fa/fa rats. Aging increased cytosolic lipin-1 content in both, obese rats and their lean controls. Also, old obese rats had decreased level of nuclear extract lipin-1compared to that in old lean rats. Neither obesity nor age altered NF-κB p65 protein content in cytosol and nuclear extract of quadriceps muscle suggesting that obesity/aging-induced changes in FA handling are not accompanied by NF-κB-mediated inflammation. Increase in plasma membrane FAT/CD36 content in obese rats and failure in lipin-1 export to nucleus with progression of obesity, implying an increase in FA uptake and their different channeling into lipid intermediates synthesis pathway in old fa/fa rats versus FA usage in lean rats of the same age.