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Lotus Leaf Aqueous Extract Reduces Visceral Fat Mass and Ameliorates Insulin Resistance in HFD-Induced Obese Rats by Regulating PPAR?2 Expression.

ABSTRACT: Objectives: Lotus leaf is a kind of traditional Chinese medicine. We aimed to explore the effects of lotus leaf aqueous extract (LLAE) on peroxisome proliferative activated receptor ?2 (PPAR?2) expression in preadipocytes and adipocytes and further investigate its effects on high fat diet (HFD)-induced obese rats. Methods: pGL3-Enhancer-PPAR?2 (625 bp)-Luc plasmid, a luciferase reporter gene expression plasmid containing PPAR?2 promoter, was stably transfected into 3T3-L1 preadipocytes. PPAR?2 promoter activities were determined by assaying the luciferase activities. Then PPAR?2 promoter activities in preadipocytes and PPAR?2 mRNA levels in human subcutaneous adipocytes were measured after the administration with LLAE. Additionally, the effects of LLAE on body weight, fat mass, glucose and lipid metabolism and the expression of PPAR?2, insulin receptor substrate 1 and glucose transporter 4 (GLUT4) in visceral adipose tissue (VAT) were measured in HFD-induced obese rats treated with low or high dose [0.5 or 3.0 g crude drug/(kg.d)] LLAE for 6 weeks. Results: Ten ?g/ml LLAE significantly increased the luciferase activities in 3T3-L1 cells and the stimulatory action reached 2.51 folds of controls when LLAE was 1000 ?g/ml (P < 0.01). After treating 3T3-L1 cells with 100 ?g/ml LLAE, the stimulatory role peaked at 32 h where it was 2.58 folds of controls (P < 0.01). Besides, 100 ?g/ml LLAE significantly increased PPAR?2 mRNA levels in human adipocytes to 1.91 folds of controls (P < 0.01). In HFD-induced obese rats, administration with both low and high dose LLAE notably reduced visceral fat mass by 45.5 and 58.4%, respectively, and significantly decreased fasting serum insulin levels (P < 0.05). The high dose LLAE also significantly decreased homeostasis model assessment of insulin resistance in obese rats (P < 0.05). Furthermore, the mRNA levels of PPAR?2 and GLUT4 in VAT of obese rats were significantly increased when compared with control rats, and were notably suppressed by LLAE intervention for 6 weeks (P < 0.05). Conclusion: LLAE significantly reduces visceral fat mass and ameliorates insulin resistance in HFD-induced obese rats. These beneficial effects of LLAE may associate with its role in stimulating PPAR?2 expression in preadipocytes and subcutaneous adipocytes and suppressing PPAR?2 and GLUT4 expression in VAT.

SUBMITTER: Yan K

PROVIDER: S-EPMC5481353 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Lotus Leaf Aqueous Extract Reduces Visceral Fat Mass and Ameliorates Insulin Resistance in HFD-Induced Obese Rats by Regulating PPARγ2 Expression.

Yan Kemin K Zhu Huijuan H Xu Jian J Pan Hui H Li Naishi N Wang Linjie L Yang Hongbo H Liu Meijuan M Gong FengYing F

Frontiers in pharmacology 20170623

<b>Objectives:</b> Lotus leaf is a kind of traditional Chinese medicine. We aimed to explore the effects of lotus leaf aqueous extract (LLAE) on peroxisome proliferative activated receptor γ2 (PPARγ2) expression in preadipocytes and adipocytes and further investigate its effects on high fat diet (HFD)-induced obese rats. <b>Methods:</b> pGL3-Enhancer-PPARγ2 (625 bp)-Luc plasmid, a luciferase reporter gene expression plasmid containing PPARγ2 promoter, was stably transfected into 3T3-L1 preadipoc ...[more]

PMID: 28690544

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Project description:BackgroundBeige adipocytes comprise a unique thermogenic cell type in the white adipose tissue (WAT) of rodents and humans, and play a critical role in energy homeostasis. In this scenario, recruitment of beige cells has been an important focus of interest for the development of novel therapeutic strategies to treat obesity. PPAR? activation by full agonists (thiazolidinediones, TZDs) drives the appearance of beige cells, a process so-called browning of WAT. However, this does not translate into increased energy expenditure, and TZDs are associated with weight gain. Partial PPAR? agonists, on the other hand, do not induce weight gain, but have not been shown to drive WAT browning. The present study was designed to investigate the effects of GQ-16 on BAT and on browning of WAT in obese mice.MethodsMale Swiss mice with obesity and hyperglycemia induced by high fat diet were treated with vehicle, rosiglitazone (4 mg/kg/d) or the TZD-derived partial PPAR? agonist GQ-16 (40 mg/kg/d) for 14 days. Fasting blood glucose, aspartate aminotransferase, alanine aminotransferase and lipid profile were measured. WAT and brown adipose tissue (BAT) depots were excised for determination of adiposity, relative expression of Ucp-1, Cidea, Prdm16, Cd40 and Tmem26 by RT-qPCR, histological analysis, and UCP-1 protein expression analysis by immunohistochemistry. Liver samples were also removed for histological analysis and determination of hepatic triglyceride content.ResultsGQ-16 treatment reduced high fat diet-induced weight gain in mice despite increasing energy intake. This was accompanied by reduced epididymal fat mass, reduced liver triglyceride content, morphological signs of increased BAT activity, increased expression of thermogenesis-related genes in interscapular BAT and epididymal WAT, and increased UCP-1 protein expression in interscapular BAT and in epididymal and inguinal WAT.ConclusionThis study suggests for the first time that a partial PPAR? agonist may increase BAT activity and induce the expression of thermogenesis-related genes in visceral WAT.General significanceThese findings suggest that PPAR? activity might be modulated by partial agonists to induce WAT browning and treat obesity.

Project description:Leaves of Passiflora suberosa L. (Family: Passifloraceae; common name: wild passion fruit, devil's pumpkin) are used in Sri Lankan traditional medicine for treating diabetes. The present study investigated the in vivo ability of P. suberosa leaves to manage blood sugar status and associated cholesterol levels. Mechanisms of action and toxicity were also determined. Phytochemical screening of aqueous extracts of P. suberosa leaves and carbohydrate content of the leaves were determined according to previously published methods. In two group of male mice (n = 9), effects on fasting and random blood glucose levels (BGLs) of different acute doses (0, 25, 50, 100 and 200 mg/kg) of the aqueous leaf extract (ALE) were evaluated at 1, 3, and 5 h post-treatment. In another set of mice, the fasting BGL was evaluated following treatment of 0 or 50 mg/kg ALE (dose prescribed in traditional medicine) for 30 consecutive days. The lipid profile, some mechanism of ALE action (diaphragm glucose uptake, glycogen content in the liver and skeletal muscles) and its toxicity (behavioural observation, food and water intake, hepatoxicity) were also assessed following 30-day treatment. However, sucrose and glucose tolerance tests and intestinal glucose uptake were conducted to determine portion of mechanisms of action following single dose of 50 mg/kg ALE. Phytochemical screening revealed the presence of alkaloids, unsaturated sterols, triterpenes, saponins, flavonoids, tannins and proanthocyanidins. Carbohydrate content of the leaves was 12.97%. The maximum hypoglycemic effect was observed after 4 h of 50 and 100 mg/kg ALE administration. The extract decreased fasting BGL (18%) following an oral sucrose challenge and inhibited (79%) glucose absorption from the intestine. Correspondingly, the levels of glycogen in the liver (61%) and in the skeletal muscles (57%) were found be higher than that of the control group. The levels of total cholesterol (17%) and tri-glyceraldehyde levels (12%) found to be reduced in treated groups. Furthermore, no significant toxic effects were observed in treated groups. The present results suggest that the leaves of P. suberosa can be used to manage blood glucose and cholesterol levels. Isolation of active compounds are recommended for further analysis.

Dataset Information

Lotus Leaf Aqueous Extract Reduces Visceral Fat Mass and Ameliorates Insulin Resistance in HFD-Induced Obese Rats by Regulating PPAR?2 Expression.

Publications

Lotus Leaf Aqueous Extract Reduces Visceral Fat Mass and Ameliorates Insulin Resistance in HFD-Induced Obese Rats by Regulating PPARγ2 Expression.

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