Skeletal Muscle Uncoupling Proteins in Mice Models of Obesity

Abstract

Obesity and accompanying type 2 diabetes are among major and increasing worldwide problems that occur fundamentally due to excessive energy intake during its expenditure. Endotherms continuously consume a certain amount of energy to maintain core body temperature via thermogenic processes, mainly in brown adipose tissue and skeletal muscle. Skeletal muscle glucose utilization and heat production are significant and directly linked to body glucose homeostasis at rest, and especially during physical activity. However, this glucose balance is impaired in diabetic and obese states in humans and mice, and manifests as glucose resistance and altered muscle cell metabolism. Uncoupling proteins have a significant role in converting electrochemical energy into thermal energy without ATP generation. Different homologs of uncoupling proteins were identified, and their roles were linked to antioxidative activity and boosting glucose and lipid metabolism. From this perspective, uncoupling proteins were studied in correlation to the pathogenesis of diabetes and obesity and their possible treatments. Mice were extensively used as model organisms to study the physiology and pathophysiology of energy homeostasis. However, we should be aware of interstrain differences in mice models of obesity regarding thermogenesis and insulin resistance in skeletal muscles. Therefore, in this review, we gathered up-to-date knowledge on skeletal muscle uncoupling proteins and their effect on insulin sensitivity in mouse models of obesity and diabetes.

Protective Role of Mitochondrial Uncoupling Proteins against Age-Related Oxidative Stress in Type 2 Diabetes Mellitus

“…UCPs are a family of mitochondrial anion carrier proteins located in the inner mitochondrial membrane that are encoded by SLC25 genes [ 162 ]. They are known to regulate glucose and lipid metabolism [ 35 ]. UCPs transport protons (H + ) to the mitochondrial matrix, thereby dissipating the proton motive force and uncoupling ATP synthesis from substrate oxidation [ 34 ].…”

“…The most diverse spectrum of UCPs is found in the mitochondria of skeletal muscle, which express all five UCPs. For this reason, skeletal muscle is one of the best-studied tissues in regard to advancing our knowledge of UCP function and associated pathologies [ 35 , 36 ]. UCPs have been intensively studied in the last three decades because of their involvement in glucose and lipid metabolism [ 37 , 38 , 39 , 40 , 41 , 42 , 43 ].…”