scholarly journals Dihydropyranocoumarins Exerted Anti-Obesity Activity In Vivo and its Activity Was Enhanced by Nanoparticulation with Polylactic-Co-Glycolic Acid

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 3053
Author(s):  
Hossin ◽  
Inafuku ◽  
Oku
Keyword(s):  
High Fat Diet ◽  
Glycolic Acid ◽  
Body Weight Gain ◽  
Oral Intake ◽  
Mrna Levels ◽  
High Fat ◽  
Mean Size ◽  
The Mean ◽  
Plga Nanoparticle

Dihydropyranocoumarins (DPCs) were isolated from Peucedanum japonicum Thunb as anti-obesity compounds in 3T3-L1 adipocytes assay; however, it is uncertain whether DPC exerts anti-obesity activity in vivo. Therefore, this study evaluated the oral intake of pure DPCs in mice fed a high-fat diet, and also attempted to enhance its activity by nanoparticulation. Increases in body weight gain and fat accumulation in white adipose tissues were significantly suppressed by the dietary intake of DPCs (1.943 mg/mouse/day). DPCs intake also significantly decreased the mean size of adipocytes and upregulated mRNA levels of thermogenesis-related genes. Nanoparticulation of DPCs with polylactic-co-glycolic acid (PLGA) dramatically increased its activity almost 100-fold over that of a non-nanoparticulated form. Thus, our findings clearly demonstrated the anti-obesity activity of DPCs in vivo and suggested that PLGA nanoparticle encapsulation was useful to enhance the anti-obesity activity of DPCs with the aim to develop natural and safe anti-obesity agents.

scholarly journals Extract of Wax Gourd Peel Prevents High-Fat Diet-Induced Hyperlipidemia in C57BL/6 Mice via the Inhibition of the PPARγPathway

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ming Gu ◽  
Shengjie Fan ◽  
Gaigai Liu ◽  
Lu Guo ◽  
Xiaobo Ding ◽  
...  
Keyword(s):  
Blood Glucose ◽  
High Fat Diet ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Fasting Blood Glucose ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
High Fat ◽  
Wax Gourd

Wax gourd is a popular vegetable in East Asia. In traditional Chinese medicine, wax gourd peel is used to prevent and treat metabolic diseases such as hyperlipidemia, hyperglycemia, obesity, and cardiovascular disease. However, there is no experimental evidence to support these applications. Here, we examined the effect of the extract of wax gourd peel (EWGP) on metabolic disorders in diet-induced C57BL/6 obese mice. In the preventive experiment, EWGP blocked body weight gain and lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), liver TG and TC contents, and fasting blood glucose in mice fed with a high-fat diet. In the therapeutic study, we induced obesity in the mice and treated with EWGP for two weeks. We found that EWGP treatment reduced serum and liver triglyceride (TG) contents and fasting blood glucose and improved glucose tolerance in the mice. Reporter assay and gene expression analysis showed that EWGP could inhibit peroxisome proliferator-activated receptorγ(PPARγ) transactivities and could decrease mRNA levels of PPARγand its target genes. We also found that HMG-CoA reductase (HMGCR) was downregulated in the mouse liver by EWGP. Our data suggest that EWGP lowers hyperlipidemia of C57BL/6 mice induced by high-fat diet via the inhibition of PPARγand HMGCR signaling.

scholarly journals Anti-Obesity Effect of Diphlorethohydroxycarmalol Isolated from Brown Alga Ishige okamurae in High-Fat Diet-Induced Obese Mice

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 637 ◽  
Author(s):  
Yuling Ding ◽  
Lei Wang ◽  
SeungTae Im ◽  
Ouibo Hwang ◽  
Hyun-Soo Kim ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Body Weight Gain ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Epididymal Adipose Tissue ◽  
High Fat ◽  
Expression Levels ◽  
Ishige Okamurae

Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current study explored the effect of DPHC on high-fat diet (HFD)-induced obesity in C57BL/6J mice. The results indicated that oral administration of DPHC (25 and 50 mg/kg/day for six weeks) significantly and dose-dependently reduced HFD-induced adiposity and body weight gain. DPHC not only decreased the levels of triglyceride, low-density lipoprotein cholesterol, leptin, and aspartate transaminase but also increased the level of high-density lipoprotein cholesterol in the serum of HFD mice. In addition, DPHC significantly reduced hepatic lipid accumulation by reduction of expression levels of the critical enzymes for lipogenesis including SREBP-1c, FABP4, and FAS. Furthermore, DPHC remarkably reduced the adipocyte size, as well as decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes including PPARγ, C/EBPα, SREBP-1c, FABP4, and FAS, which regulate the lipid metabolism in the epididymal adipose tissue (EAT). Further studies demonstrated that DPHC significantly stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in both liver and EAT. These results demonstrated that DPHC effectively prevented HFD-induced obesity and suggested that DPHC could be used as a potential therapeutic agent for attenuating obesity and obesity-related diseases.

scholarly journals Paradoxical resistance to high-fat diet-induced obesity and altered macrophage polarization in mineralocorticoid receptor-overexpressing mice

2014 ◽  
Vol 306 (1) ◽  
pp. E75-E90 ◽  
Author(s):  
Emmanuelle Kuhn ◽  
Christine Bourgeois ◽  
Vixra Keo ◽  
Say Viengchareun ◽  
Adeline Muscat ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Mineralocorticoid Receptor ◽  
Body Weight Gain ◽  
Macrophage Polarization ◽  
Metabolic Phenotype ◽  
High Fat ◽  
Glucocorticoid Signaling ◽  
Lower Body Weight

The mineralocorticoid receptor (MR) exerts proadipogenic and antithermogenic effects in vitro, yet its in vivo metabolic impact remains elusive. Wild type (WT) and transgenic (Tg) mice overexpressing human MR were subjected to standard chow (SC) or high-fat diet (HFD) for 16 wk. Tg mice had a lower body weight gain than WT animals and exhibited a relative resistance to HFD-induced obesity. This was associated with a decrease in fat mass, an increased population of smaller adipocytes, and an improved glucose tolerance compared with WT animals. Quantitative RT-PCR studies revealed decreased expression of PPARγ2, a master adipogenic gene, and of glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase type 1, consistent with an impaired local glucocorticoid signaling in adipose tissues (AT). This paradoxical resistance to HFD-induced obesity was not related to an adipogenesis defect since differentiation capacity of Tg preadipocytes isolated from stroma-vascular fractions was unaltered, suggesting that other nonadipocyte factors might compromise AT development. Although AT macrophage infiltration was not different between genotypes, Tg mice exhibited a distinct macrophage polarization, as revealed by FACS analysis and CD11c/CD206 expression studies. We further demonstrated that Tg macrophage-conditioned medium partially impaired preadipocyte differentiation. Therefore, we propose that modification of M1/M2 polarization of hMR-overexpressing macrophages could account in part for the metabolic phenotype of Tg mice. Collectively, our results provide evidence that MR exerts a pivotal immunometabolic role by controlling adipocyte differentiation processes directly but also indirectly through macrophage polarization regulation. Our findings should be taken into account for the pharmacological treatment of metabolic disorders.

scholarly journals Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Yi Tao ◽  
Hongliang Zhang ◽  
Bing Gao ◽  
Jiao Guo ◽  
Yinming Hu ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Chitosan Nanoparticles ◽  
Plasma Viscosity ◽  
Water Soluble ◽  
Lipid Lowering ◽  
Sprague Dawley ◽  
High Fat ◽  
Sprague Dawley Rats ◽  
Mean Size ◽  
The Mean

Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC) has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs) on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800 nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD) activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia.

scholarly journals The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenyun Zeng ◽  
Danbin Wu ◽  
Yingxin Sun ◽  
Yanrong Suo ◽  
Qun Yu ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
In Vitro Study ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
High Fat ◽  
Nlrp3 Inflammasome Activation ◽  
Atherosclerosis Development

AbstractNLRP3 inflammasome is a vital player in macrophages pyroptosis, which is a type of proinflammatory cell-death and takes part in the pathogenesis of atherosclerosis. In this study, we used apoE−/− mice and ox-LDL induced THP-1 derived macrophages to explore the mechanisms of MCC950, a selective NLRP3 inhibitor in treating atherosclerosis. For the in vivo study, MCC950 was intraperitoneal injected to 8-week-old apoE−/− mice fed with high-fat diet for 12 weeks. For the in vitro study, THP-1 derived macrophages were treated with ox-LDL and MCC950 for 48 h. MCC950 administration reduced plaque areas and macrophages contents, but did not improve the serum lipid profiles in aortic root of apoE−/− mice. MCC950 inhibited the activation of NLRP3/ASC/Caspase-1/GSDMD-N axis, and alleviated macrophages pyroptosis and the production of IL-1β and IL-18 both in aorta and in cell lysates. However, MCC950 did not affect the expression of TLR4 or the mRNA levels of NLRP3 inflammasome and its downstream proteins, suggesting that MCC950 had no effects on the priming of NLRP3 inflammasome activation in macrophages. The anti-atherosclerotic mechanisms of MCC950 on attenuating macrophages inflammation and pyroptosis involved in inhibiting the assembly and activation of NLRP3 inflammasome, rather than interrupting its priming.

scholarly journals GIP receptor antagonist treatment causes weight loss in ovariectomized high fat diet-fed mice

2021 ◽  
Author(s):  
Geke Aline Boer ◽  
Jenna Hunt ◽  
Maria Gabe ◽  
Johanne Windeløv ◽  
Alexander Sparre-Ulricht ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Pharmacokinetic Profile ◽  
High Fat ◽  
Ovariectomized Mice ◽  
Gip Receptor

Background and purpose The incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), secreted by the enteroendocrine K-cells in the proximal intestine, may regulate lipid metabolism and adiposity but its exact role in these processes is unclear. Experimental approach We characterized in vitro and in vivo antagonistic properties of a novel GIP analogue, mGIPAnt-1. We further assessed the in vivo pharmacokinetic profile of this antagonist, as well as its ability to affect high-fat diet (HFD)-induced body weight gain in ovariectomized mice during an 8-week treatment period. Key results mGIPAnt-1 showed competitive antagonistic properties to the GIP receptor (GIPR) in vitro as it inhibited GIP-induced cAMP accumulation in COS-7 cells. Furthermore, mGIPAnt-1 was capable of inhibiting GIP-induced glucoregulatory and insulinotropic effects in vivo and has a favourable pharmacokinetic profile with a half-life of 7.2 hours in C57Bl6 female mice. Finally, sub-chronic treatment with mGIPAnt-1 in ovariectomized HFD mice resulted in a reduction of body weight and fat mass. Conclusion and Implications mGIPAnt-1 successfully inhibited acute GIP-induced effects in vitro and in vivo and sub-chronically induces resistance to HFD-induced weight gain in ovariectomized mice. Our results support the development of GIP antagonists for the therapy of obesity.

scholarly journals Anti-obesity effect of Tamarindus indicus seed extract against a high-fat diet-induced obese model in rats

2020 ◽  
Vol 11 (2) ◽  
pp. 2083-2089
Author(s):  
Nabeel K ◽  
Asra Fathima ◽  
Farhath Khanum ◽  
Manjula S N ◽  
Mruthunjaya K ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Seed Extract ◽  
The Body ◽  
High Fat ◽  
Cell Viability Assay ◽  
Serum Triglycerides

The present study was aimed to evaluate the anti-obesity property of Tamarindus indica seed extract (TSE) on high fat-fed obese rats. TSE was prepared by cold maceration method and qualitative phytochemical studies had been carried out. In vitro cell viability assay (MTT assay) was and oil red staining for evaluating the lipid accumulation in cells was carried out using 3T3-L1 cells, and leptin levels was evaluated by ELISA. In-vivo Obesity was induced in experimental rats by administration of a high-fat diet for 04 weeks. The anti-obesity effect was screened by oral administration of TSE at two different dose levels i.e., 250 and 500mg/kg b. Wt. Along with a high-fat diet for a period of 04 weeks. The anti-obesity activity is estimated in terms of body weight gain, serum triglycerides (TG), Total cholesterol (TC). In -vitro studies revealed that the TSE has no cytotoxic effect, Administration of a high-fat diet for 04 weeks significantly increased the body weight, serum triglycerides, cholesterol. Upon treatment with TSE, a significant dose-dependent alteration in body weight, triglycerides, cholesterol levels were observed, inferring the anti-obesity property of Tamarindus seed extract.

scholarly journals Lactobacillus Brevis OPK-3 from Kimchi Prevents Obesity and Modulates the Expression of Adipogenic and Pro-Inflammatory Genes in Adipose Tissue of Diet-Induced Obese Mice

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 604 ◽  
Author(s):  
Jung Eun Park ◽  
Suk-Heung Oh ◽  
Youn-Soo Cha
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Epididymal Adipose Tissue ◽  
Pcr Analysis ◽  
Distilled Water ◽  
Mrna Levels ◽  
High Fat

Our previous study reported that lactic acid bacteria (L. brevis OPK-3) isolated from kimchi ameliorated intracellular lipid accumulation in 3T3-L1 adipocyte. The current study explored potential roles of L. brevis OPK-3 (KLAB) on preventing body weight gain and its effect on the inflammatory response of adipose tissue. Male C57BL/6 mice (n = 10) were divided into four groups: normal diet with distilled water (NDC), high-fat diet with distilled water (HDC), high-fat diet with L-ornithine (OTC) or high-fat diet with KLAB. The KLAB supplement resulted in significantly lower body weight, lower epididymal fat tissue mass, and lower serum and hepatic TG levels than the HDC. KLAB supplementation improved serum cytokines, and real-time polymerase chain reaction (PCR) analysis showed significantly lower inflammatory cytokine mRNA levels in epididymal adipose tissue. These results suggest that the administration of KLAB inhibits the induction of inflammation in adipose tissue along with the inhibition of weight gain. Therefore, this study demonstrates the therapeutic and beneficial value of this strain produced during the fermentation of kimchi.

Mice deleted for GPAT3 have reduced GPAT activity in white adipose tissue and altered energy and cholesterol homeostasis in diet-induced obesity

2014 ◽  
Vol 306 (10) ◽  
pp. E1176-E1187 ◽  
Author(s):  
Jingsong Cao ◽  
Sylvie Perez ◽  
Bryan Goodwin ◽  
Qingcong Lin ◽  
Haibing Peng ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Cholesterol Metabolism ◽  
Body Weight Gain ◽  
Cholesterol Homeostasis ◽  
High Fat

Glycerol-3-phosphate acyltransferases (GPATs) catalyze the first step in the synthesis of glycerolipids and glycerophospholipids. Microsomal GPAT, the major GPAT activity, is encoded by at least two closely related genes, GPAT3 and GPAT4. To investigate the in vivo functions of GPAT3, we generated Gpat3-deficient ( Gpat3 −/−) mice. Total GPAT activity in white adipose tissue of Gpat3 −/− mice was reduced by 80%, suggesting that GPAT3 is the predominant GPAT in this tissue. In liver, GPAT3 deletion had no impact on total GPAT activity but resulted in a 30% reduction in N-ethylmaleimide-sensitive GPAT activity. The Gpat3 −/− mice were viable and fertile and exhibited no obvious metabolic abnormalities on standard laboratory chow. However, when fed a high-fat diet, female Gpat3 −/− mice showed decreased body weight gain and adiposity and increased energy expenditure. Increased energy expenditure was also observed in male Gpat3 −/− mice, although it was not accompanied by a significant change in body weight. GPAT3 deficiency lowered fed, but not fasted, glucose levels and tended to improve glucose tolerance in diet-induced obese male and female mice. On a high-fat diet, Gpat3 −/− mice had enlarged livers and displayed a dysregulation in cholesterol metabolism. These data establish GPAT3 as the primary GPAT in white adipose tissue and reveal an important role of the enzyme in regulating energy, glucose, and lipid homeostasis.

scholarly journals Formononetin, an isoflavone, activates AMP-activated protein kinase/β-catenin signalling to inhibit adipogenesis and rescues C57BL/6 mice from high-fat diet-induced obesity and bone loss

2017 ◽  
Vol 117 (5) ◽  
pp. 645-661 ◽  
Author(s):  
Jyoti Gautam ◽  
Vikram Khedgikar ◽  
Priyanka Kushwaha ◽  
Dharmendra Choudhary ◽  
Geet Kumar Nagar ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Bone Loss ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Binding Protein ◽  
Regulatory Element ◽  
Adipogenic Differentiation ◽  
High Fat ◽  
Amp Activated Protein Kinase

AbstractBalance between adipocyte and osteoblast differentiation is the key link of disease progression in obesity and osteoporosis. We have previously reported that formononetin (FNT), an isoflavone extracted from Butea monosperma, stimulates osteoblast formation and protects against postmenopausal bone loss. The inverse relationship between osteoblasts and adipocytes prompted us to analyse the effect of FNT on adipogenesis and in vivo bone loss, triggered by high-fat diet (HFD)-induced obesity. The anti-obesity effect and mechanism of action of FNT was determined in 3T3-L1 cells and HFD-induced obese male mice. Our findings show that FNT suppresses the adipogenic differentiation of 3T3-L1 fibroblasts, through down-regulation of key adipogenic markers such as PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα) and sterol regulatory element-binding protein (SREBP) and inhibits intracellular TAG accumulation. Increased intracellular reactive oxygen species levels and AMP-activated protein kinase (AMPK) activation accompanied by stabilisation of β-catenin were attributed to the anti-adipogenic action of FNT. In vivo, 12 weeks of FNT treatment inhibited the development of obesity in mice by attenuating HFD-induced body weight gain and visceral fat accumulation. The anti-obesity effect of FNT results from increased energy expenditure. FNT also protects against HFD-induced dyslipidaemia and rescues deterioration of trabecular bone volume by increasing bone formation and decreasing bone resorbtion caused by HFD. FNT’s rescuing action against obesity-induced osteoporosis commenced at the level of progenitors, as bone marrow progenitor cells, obtained from the HFD mice group supplemented with FNT, showed increased osteogenic and decreased adipogenic potentials. Our findings suggest that FNT inhibits adipogenesis through AMPK/β-catenin signal transduction pathways and protects against HFD-induced obesity and bone loss.

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