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Exercise protects against diet-induced insulin resistance through downregulation of protein kinase C? in mice.

ABSTRACT: Physical exercise is an important and effective therapy for diabetes. However, its underlying mechanism is not fully understood. Protein kinase C? (PKC?) has been suggested to be involved in the pathogenesis of obesity and insulin resistance, but the role of PKC? in exercise-induced improvements in insulin resistance is completely unknown. In this study, we evaluated the involvement of PKC? in exercise-attenuated insulin resistance in high-fat diet (HFD)-fed mice. PKC?(-/-) and wild-type mice were fed a HFD with or without exercise training. PKC protein expression, body and tissue weight change, glucose and insulin tolerance, metabolic rate, mitochondria size and number, adipose inflammation, and AKT activation were determined to evaluate insulin sensitivity and metabolic changes after intervention. PKC? expression decreased in both skeletal muscle and liver tissue after exercise. Exercise and PKC? deficiency can alleviate HFD-induced insulin resistance, as evidenced by improved insulin tolerance. In addition, fat accumulation and mitochondrial dysfunction induced by HFD were also ameliorated by both exercise and PKC? deficiency. On the other hand, exercise had little effect on PKC?(-/-) mice. Further, our data indicated improved activation of AKT, the downstream signal molecule of insulin, in skeletal muscle and liver of exercised mice, whereas PKC? deficiency blunted the difference between sedentary and exercised mice. These results suggest that downregulation of PKC? contributes to exercise-induced improvement of insulin resistance in HFD-fed mice.

SUBMITTER: Rao X

PROVIDER: S-EPMC3857188 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Exercise protects against diet-induced insulin resistance through downregulation of protein kinase Cβ in mice.

Rao Xiaoquan X Zhong Jixin J Xu Xiaohua X Jordan Brianna B Maurya Santosh S Braunstein Zachary Z Wang Tse-Yao TY Huang Wei W Aggarwal Sudha S Periasamy Muthu M Rajagopalan Sanjay S Mehta Kamal K Sun Qinghua Q

PloS one 20131209 12

Physical exercise is an important and effective therapy for diabetes. However, its underlying mechanism is not fully understood. Protein kinase Cβ (PKCβ) has been suggested to be involved in the pathogenesis of obesity and insulin resistance, but the role of PKCβ in exercise-induced improvements in insulin resistance is completely unknown. In this study, we evaluated the involvement of PKCβ in exercise-attenuated insulin resistance in high-fat diet (HFD)-fed mice. PKCβ(-/-) and wild-type mice we ...[more]

PMID: 24349059

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Project description:Background/objectivesVisceral adiposity is associated with increased diabetes risk, while expansion of subcutaneous adipose tissue may be protective. However, the visceral compartment contains different fat depots. Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot. Here, we aimed to define PAT functionality in lean and high-fat-diet (HFD)-induced obese mice.Subjects/methodsFour adipose tissue depots (inguinal, mesenteric, gonadal, and peripancreatic adipose tissue) from chow- and HFD-fed male mice were compared with respect to adipocyte size (n = 4-5/group), cellular composition (FACS analysis, n = 5-6/group), lipogenesis and lipolysis (n = 3/group), and gene expression (n = 6-10/group). Radioactive tracers were used to compare lipid and glucose metabolism between these four fat depots in vivo (n = 5-11/group). To determine the role of PAT in obesity-associated metabolic disturbances, PAT was surgically removed prior to challenging the mice with HFD. PAT-ectomized mice were compared to sham controls with respect to glucose tolerance, basal and glucose-stimulated insulin levels, hepatic and pancreatic steatosis, and gene expression (n = 8-10/group).ResultsWe found that PAT is a tiny fat depot (~0.2% of the total fat mass) containing relatively small adipocytes and many "non-adipocytes" such as leukocytes and fibroblasts. PAT was distinguished from the other fat depots by increased glucose uptake and increased fatty acid oxidation in both lean and obese mice. Moreover, PAT was the only fat depot where the tissue weight correlated positively with liver weight in obese mice (R = 0.65; p = 0.009). Surgical removal of PAT followed by 16-week HFD feeding was associated with aggravated hepatic steatosis (p = 0.008) and higher basal (p < 0.05) and glucose-stimulated insulin levels (p < 0.01). PAT removal also led to enlarged pancreatic islets and increased pancreatic expression of markers of glucose-stimulated insulin secretion and islet development (p < 0.05).ConclusionsPAT is a small metabolically highly active fat depot that plays a previously unrecognized role in the pathogenesis of hepatic steatosis and insulin resistance in advanced obesity.

Dataset Information

Exercise protects against diet-induced insulin resistance through downregulation of protein kinase C? in mice.

Publications

Exercise protects against diet-induced insulin resistance through downregulation of protein kinase Cβ in mice.

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