Abstract
ObjectiveObesity-related diseases such as diabetes, hypertension, dyslipidemia, and cardiovascular diseases have increased due to the obesity epidemic. Early intervention for obesity through lifestyle and nutrition plays an important role in preventing obesity-related diseases. Therefore, the purpose of this study is to explore the role of leucine and exercise in adiposity, systemic insulin resistance, and inflammation to provide theoretical and guiding basis for the early prevention and treatment of obesity.MethodsC57BL/6J male mice were randomly divided into HFD or LFD-fed mice group. After 9 weeks, glucose tolerance test (GTT) was performed to detect their systemic insulin sensitivity. Starting from week 10, mice were divided into eight groups and treated with moderate exercise or/and 1.5% leucine. At week 13, systemic insulin sensitivity was detected by GTT. At week 14, mice were dissected to analyze adiposity and inflammation.ResultsIn LFD mice, exercise significantly increased systemic insulin sensitivity by increasing GLUT4 expression in the muscle and decreasing adiposity through increasing AMPK phosphorylation in adipose tissue. In HFD mice, the simultaneous intervention of exercise and leucine increases systemic insulin sensitivity by reducing liver and adipose tissue inflammation via decreasing NF-κB p65 phosphorylation, and increasing the expression of adiponectin in adipose tissue.ConclusionThere are different mechanisms underlying the effects of exercise and leucine on insulin resistance and inflammation in LFD-fed mice or HFD-fed mice.
Highlights
Obesity is one of the most serious health problems in many countries
Compared with the weight of white adipose tissue of mice on high fat diet (HFD) and low-fat diet fed (LFD), adiposity including epididymal fat, perirenal fat, and mesenteric fat of mice fed with HFD increased significantly (Supplementary Data and Figures S1B, C)
According to glucose tolerance test (GTT) experiment, the fasting baseline blood glucose level of mice fed with HFD was higher than that of LFD, and the difference of glucose level at 30 and 60 min was statistically significant (Supplementary Data and Figure S1D)
Summary
Obesity is one of the most serious health problems in many countries. Due to the prevalence of obesity beginning in childhood, the incidence of metabolic diseases such as diabetes, non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), and some cancer will continue to increase [1]. The root of metabolic diseases includes the increased energy intake, Different Mechanisms in Insulin Sensitivity especially high fat and high refined carbohydrate consumption, and sedentary lifestyle [2, 3]. More and more evidence show that inflammation is the main cause of over-nutrition induced insulin resistance and type 2 diabetes [4]. Speaking, over-nutrition can activate the inflammatory signal pathway and release a large number of inflammatory cytokines to interfere with signal transduction, inducing adipose tissue [7] and liver [8] inflammation, which is a major reason for systemic insulin resistance. Insulin resistance aggravates adipose tissue [9] and liver [10] inflammation It leads to a vicious spiral and promotes the development of type 2 diabetes
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