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Liraglutide protects cardiac function in diabetic rats through the PPAR? pathway.

ABSTRACT: Increasing evidence shows that diabetes causes cardiac dysfunction. We hypothesized that a glucagon-like peptide-1 analogue, liraglutide, would attenuate cardiac dysfunction in diabetic rats. Twenty-four Sprague Dawley (SD) rats were divided into 2 groups fed either a normal diet (normal, n = 6) or a high-fat diet (HFD, n = 18) for 4 weeks. Then, the HFD rats were injected with streptozotocin (STZ) to create a diabetic rat model. Diabetic rats were divided into 3 subgroups receiving vehicle (diabetic, n = 6), a low dose of liraglutide (Llirag, 0.2 mg/kg/day, n = 6) or a high dose of liraglutide (Hlirag, 0.4 mg/kg/day, n = 6). Metabolic parameters, systolic blood pressure, heart rate, left ventricular (LV) function, and whole genome expression of the heart were determined. Diabetic rats developed insulin resistance, increased blood lipid levels and oxidative stress, and impaired LV function, serum adiponectin, NO. Liraglutide improved insulin resistance, serum adiponectin, NO, heart rate and LV function and reduced blood triglyceride, total cholesterol levels and oxidative stress. Moreover, liraglutide increased heart Nr1h3 , Ppar-? and Srebp expression and reduced Dgat , and Angptl3 expression. Liraglutide prevented in cardiac dysfunction by activating the PPAR? pathway to inhibit Dgat expression and oxidative stress in diabetic rats.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC5857913 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Liraglutide protects cardiac function in diabetic rats through the PPARα pathway.

Zhang Qian Q Xiao Xinhua X Zheng Jia J Li Ming M Yu Miao M Ping Fan F Wang Tong T Wang Xiaojing X

Bioscience reports 20180212

Increasing evidence shows that diabetes causes cardiac dysfunction. We hypothesized that a glucagon-like peptide-1 analogue, liraglutide, would attenuate cardiac dysfunction in diabetic rats. Twenty-four Sprague Dawley (SD) rats were divided into 2 groups fed either a normal diet (normal, n = 6) or a high-fat diet (HFD, n = 18) for 4 weeks. Then, the HFD rats were injected with streptozotocin (STZ) to create a diabetic rat model. Diabetic rats were divided into 3 subgroups receiving vehicle (dia ...[more]

PMID: 29440457

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Project description:The change of gut microbiome is associated with a serious of metabolic disorders, such as diabetes. As a glucagon-like peptide 1 analogue, liraglutide is a potent antidiabetic drug in clinical practice. However, the effect of liraglutide on the community of gut microbiota is still unknown. We aimed to determine the influence of liraglutide on fecal microbiota in diabetic male rats. Five-week-old male Sprague-Dawley rats were fed with a control diet or a high-fat diet for four weeks. By injecting streptozotocin, the diabetic rat model was performed. Diabetic male rats were injected subcutaneously with a low dose of liraglutide (liraglutide 0.2 mg/kg/day), a high dose of liraglutide (liraglutide 0.4 mg/kg/day), or normal saline for 12 weeks. Our data showed that liraglutide effectively prevented the development of diabetes in male rats. Pyrosequencing of the V3-V4 region of 16S rRNA genes manifested a remarkable transfer of gut microbiota construction in liraglutide-treated male rats compared with that of the diabetic male rats. Further analysis identified 879 liraglutide-treated specific operational taxonomic units. Some short-chain fatty acid (SCFA)-producing bacteria, including Bacteroides, Lachnospiraceae, and probiotic bacteria, Bifidobacterium, were selectively enhanced in liraglutide-treated diabetic male rats. Lactobacillus was negatively correlated with fasting blood glucose. To sum up, our findings propose that the prevention of diabetes by liraglutide in the diabetic male rats may be associated with the structural change of the gut microbiota, inflammation alleviation, and abundantly elevated SCFA-producing bacteria in the intestine. Impact statement Our findings suggest that significant changes in gut microbiota are associated with liraglutide treatment on the diabetic male rats, including enrichment of short-chain fatty acid producers and probiotic bacteria. This may help alleviate systemic inflammation and contribute to the beneficial effects of liraglutide against diabetes.

Dataset Information

Liraglutide protects cardiac function in diabetic rats through the PPAR? pathway.

Publications

Liraglutide protects cardiac function in diabetic rats through the PPARα pathway.

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