Semen Cuscutae Administration Improves Hepatic Lipid Metabolism and Adiposity in High Fat Diet-Induced Obese Mice

Since arginase has been shown to compete with nitric oxide (NO) synthase, emerging evidence has reported that arginase inhibition improves obesity by increasing NO production. Semen cuscutae (SC), which is a well-known Chinese medicine, has multiple biological functions such as anti-oxidant function and immune regulation. In this study, we investigated whether the SC as a natural arginase inhibitor influences hepatic lipid abnormalities and whole-body adiposity in high-fat diet (HFD)-induced obese mice. The lipid accumulation was significantly reduced by SC treatment in oleic acid-induced hepatic steatosis in vitro. Additionally, SC supplementation substantially lowered HFD-induced increases in arginase activity and weights of liver and visceral fat tissue, while increasing hepatic NO. Furthermore, elevated mRNA expressions of sterol regulatory element-binding transcription factor 1 (SREBP-1c), fatty-acid synthase (FAS), peroxisome proliferator-activated receptor-gamma (PPAR-γ)1, and PPAR-γ2 in HFD-fed mice were significantly attenuated by SC supplementation. Taken together, SC, as a novel natural arginase inhibitor, showed anti-obesity properties by modulating hepatic arginase and NO production and metabolic pathways related to hepatic triglyceride (TG) metabolism.

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Combination of Limosilactobacillus fermentum MG4231 and MG4244 attenuates lipid accumulation in high-fat diet-fed obese mice

Beneficial Microbes ◽

10.3920/bm2020.0205 ◽

2021 ◽

pp. 1-14

Author(s):

S.J. Kim ◽

S.-I. Choi ◽

M. Jang ◽

Y.-A. Jeong ◽

C.-H. Kang ◽

...

Keyword(s):

High Fat Diet ◽

Liver Tissue ◽

Fatty Acid Synthase ◽

Body Weight Gain ◽

Binding Protein ◽

Regulatory Element ◽

Peroxisome Proliferator ◽

Obese Mice ◽

High Fat ◽

Hepatic Atrophy

We investigated the anti-obesity effect and the underlying mechanisms of action of human-derived Limosilactobacillus fermentum MG4231, MG4244, and their combination, in high-fat diet-induced obese mice. Administration of the Limosilactobacillus strains decreased body weight gain, liver and adipose tissue weight, and glucose tolerance. Serum levels of total cholesterol, low-density lipoprotein-cholesterol, and leptin were reduced, while adiponectin increased. The administration of Limosilactobacillus strains improved the histopathological features of liver tissue, such as hepatic atrophy and inflammatory penetration, and significantly reduced the content of triglyceride in the liver. Limosilactobacillus administration discovered a significant reduction in the size of the adipocytes in the epididymal tissue. Limosilactobacillus treatment significantly reduced the expression of important regulators in lipid metabolism, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, fatty acid synthase (FAS), adipocyte-protein 2, and lipoprotein lipase in the epididymal tissue. Also, Limosilactobacillus lowered sterol regulatory element-binding protein 1-c and FAS in the liver tissue. Such changes in the expression of these regulators in both liver and epididymis tissue were caused by Limosilactobacillus upregulating phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase. Therefore, we suggest that the use of the combination of L. fermentum MG4231 and MG4244, as probiotics could effectively inhibit adipogenesis and lipogenesis from preventing obesity.

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The Antiobesity Effect ofPolygonum aviculareL. Ethanol Extract in High-Fat Diet-Induced Obese Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/626397 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Yoon-Young Sung ◽

Taesook Yoon ◽

Won-Kyung Yang ◽

Seung Ju Kim ◽

Dong-Seon Kim ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Regulatory Element ◽

Ethanol Extract ◽

Peroxisome Proliferator ◽

Dependent Manner ◽

Obese Mice ◽

High Fat ◽

Peroxisome Proliferator Activated Receptor

The antiobesity effects of aP. aviculareethanol extract (PAE) in high-fat diet- (HFD-) induced obese mice were investigated. The mice were fed an HFD or an HFD supplemented with PAE (400 mg/kg/day) for 6.5 weeks. The increased body weights, adipose tissue weight, and adipocyte area as well as serum total triglyceride, leptin, and malondialdehyde concentrations were decreased in PAE-treated HFD-induced obese mice relative to the same measurements in untreated obese mice. Furthermore, PAE significantly suppressed the elevated mRNA expression levels of sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptorγ, fatty acid synthase, and adipocyte protein 2 in the white adipose tissue of obese mice. In addition, PAE treatment of 3T3-L1 cells inhibited adipocyte differentiation and fat accumulation in a dose-dependent manner. These results suggest that PAE exerts antiobesity effects in HFD-induced obese mice through the suppression of lipogenesis in adipose tissue and increased antioxidant activity.

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Curcumin improves glycolipid metabolism through regulating peroxisome proliferator activated receptor γ signalling pathway in high-fat diet-induced obese mice and 3T3-L1 adipocytes

Royal Society Open Science ◽

10.1098/rsos.170917 ◽

2017 ◽

Vol 4 (11) ◽

pp. 170917 ◽

Cited By ~ 20

Author(s):

Yanyun Pan ◽

Dandan Zhao ◽

Na Yu ◽

Tian An ◽

Jianan Miao ◽

...

Keyword(s):

High Fat Diet ◽

Fasting Blood Glucose ◽

Signalling Pathway ◽

Peroxisome Proliferator ◽

Obese Mice ◽

High Fat ◽

Peroxisome Proliferator Activated Receptor ◽

Glycolipid Metabolism

Curcumin is an active component derived from Curcuma longa L. which is a traditional Chinese medicine that is widely used for treating metabolic diseases through regulating different molecular pathways. Here, in this study, we aimed to comprehensively investigate the effects of curcumin on glycolipid metabolism in vivo and in vitro and then determine the underlying mechanism. Male C57BL/6 J obese mice and 3T3-L1 adipocytes were used for in vivo and in vitro study, respectively. Our results demonstrated that treatment with curcumin for eight weeks decreased body weight, fat mass and serum lipid profiles. Meanwhile, it lowered fasting blood glucose and increased the insulin sensitivity in high-fat diet-induced obese mice. In addition, curcumin stimulated lipolysis and improved glycolipid metabolism through upregulating the expressions of adipose triglyceride lipase and hormone-sensitive lipase, peroxisome proliferator activated receptor γ/α (PPARγ/α) and CCAAT/enhancer binding proteinα (C/EBPα) in adipose tissue of the mice. In differentiated 3T3-L1 cells, curcumin reduced glycerol release and increased glucose uptake via upregulating PPARγ and C/EBPα. We concluded that curcumin has the potential to improve glycolipid metabolism disorders caused by obesity through regulating PPARγ signalling pathway.

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Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

Cellular Physiology and Biochemistry ◽

10.1159/000493650 ◽

2018 ◽

Vol 49 (5) ◽

pp. 1870-1884 ◽

Cited By ~ 25

Author(s):

Chian-Jiun Liou ◽

Ciao-Han Wei ◽

Ya-Ling Chen ◽

Ching-Yi Cheng ◽

Chia-Ling Wang ◽

...

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Hepatic Steatosis ◽

Lipid Accumulation ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Epididymal Adipose Tissue ◽

Obese Mice ◽

High Fat

Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

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Aerobic Exercise Increases Meteorin-Like Protein in Muscle and Adipose Tissue of Chronic High-Fat Diet-Induced Obese Mice

BioMed Research International ◽

10.1155/2018/6283932 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Ju Yong Bae

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Normal Diet ◽

Whole Body ◽

Peroxisome Proliferator ◽

Obese Mice ◽

High Fat ◽

Peripheral Tissues ◽

Body Tissues ◽

Exercise Induced

Upregulated meteorin-like (Metrnl) protein in peripheral tissues because of exercise-induced increases in intramuscular Metrnl may effectively alleviate obesity by improving metabolism in whole-body tissues. The objective was to analyse the effects of regular treadmill exercise on Metrnl levels in muscle and peripheral tissues of chronic high-fat diet- (HFD-) induced obese mice. Forty-eight-week-old male C57BL/6 mice were first divided equally into normal-diet (CO) and high-fat diet (HF) groups. Following 16 weeks of a HFD, each group was again split equally into control (CO, HF) and training groups (COT, HFT). The HFT group expressed significantly higher phospho-AMP-activated protein kinase (AMPK), AMPK activity, and peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α) in muscle tissue than the HF group (p<0.05). Similar to muscle energy sensing network protein levels, the HFT group also expressed significantly higher muscle, plasma, and adipose tissue Metrnl (p<0.05). Moreover, regular exercise increased acyl-CoA oxidase 1 (ACOX-1) and monoglyceride lipase (MGL) expression in adipose tissue (p<0.05) and significantly decreased abdominal fat mass (p<0.05). This study suggests that exercise-induced muscle Metrnl effectively reduces fat accumulation through the increase of Metrnl in adipose tissue, which may be a therapeutic target for chronic obesity.

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Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver

Nature Communications ◽

10.1038/s41467-021-22106-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

KyeongJin Kim ◽

Jin Ku Kang ◽

Young Hoon Jung ◽

Sang Bae Lee ◽

Raffaela Rametta ◽

...

Keyword(s):

Fatty Liver ◽

Whole Body ◽

Acid Oxidation ◽

Chow Diet ◽

Peroxisome Proliferator ◽

Obese Mice ◽

Ph Domain ◽

Peroxisome Proliferator Activated Receptor

AbstractIncreased adiposity confers risk for systemic insulin resistance and type 2 diabetes (T2D), but mechanisms underlying this pathogenic inter-organ crosstalk are incompletely understood. We find PHLPP2 (PH domain and leucine rich repeat protein phosphatase 2), recently identified as the Akt Ser473 phosphatase, to be increased in adipocytes from obese mice. To identify the functional consequence of increased adipocyte PHLPP2 in obese mice, we generated adipocyte-specific PHLPP2 knockout (A-PHLPP2) mice. A-PHLPP2 mice show normal adiposity and glucose metabolism when fed a normal chow diet, but reduced adiposity and improved whole-body glucose tolerance as compared to Cre- controls with high-fat diet (HFD) feeding. Notably, HFD-fed A-PHLPP2 mice show increased HSL phosphorylation, leading to increased lipolysis in vitro and in vivo. Mobilized adipocyte fatty acids are oxidized, leading to increased peroxisome proliferator-activated receptor alpha (PPARα)-dependent adiponectin secretion, which in turn increases hepatic fatty acid oxidation to ameliorate obesity-induced fatty liver. Consistently, adipose PHLPP2 expression is negatively correlated with serum adiponectin levels in obese humans. Overall, these data implicate an adipocyte PHLPP2-HSL-PPARα signaling axis to regulate systemic glucose and lipid homeostasis, and suggest that excess adipocyte PHLPP2 explains decreased adiponectin secretion and downstream metabolic consequence in obesity.

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Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet (Running Title: Sdc4 Deficiency Affects Metabolic Phenotypes)

Nutrients ◽

10.3390/nu11112810 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2810 ◽

Cited By ~ 1

Author(s):

Maria De Luca ◽

Denise Vecchie’ ◽

Baskaran Athmanathan ◽

Sreejit Gopalkrishna ◽

Jennifer A. Valcin ◽

...

Keyword(s):

Insulin Sensitivity ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Serum Triglyceride ◽

Independent Study ◽

Whole Body ◽

Elderly Subjects ◽

Sensitivity Index ◽

High Fat ◽

Metabolic Phenotypes

Syndecans are transmembrane proteoglycans that, like integrins, bind to components of the extracellular matrix. Previously, we showed significant associations of genetic variants in the Syndecan-4 (SDC4) gene with intra-abdominal fat, fasting plasma glucose levels, and insulin sensitivity index in children, and with fasting serum triglyceride levels in healthy elderly subjects. An independent study also reported a correlation between SDC4 and the risk of coronary artery disease in middle-aged patients. Here, we investigated whether deletion of Sdc4 promotes metabolic derangements associated with diet-induced obesity by feeding homozygous male and female Sdc4-deficient (Sdc4-/-) mice and their age-matched wild-type (WT) mice a high-fat diet (HFD). We found that WT and Sdc4-/- mice gained similar weight. However, while no differences were observed in males, HFD-fed female Sdc4-/- mice exhibited a higher percentage of body fat mass than controls and displayed increased levels of plasma total cholesterol, triglyceride, and glucose, as well as reduced whole-body insulin sensitivity. Additionally, they had an increased adipocyte size and macrophage infiltration in the visceral adipose tissue, and higher triglyceride and fatty acid synthase levels in the liver. Together with our previous human genetic findings, these results provide evidence of an evolutionarily conserved role of SDC4 in adiposity and its complications.

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Hepatic Lipid Accumulation Induced by a High-fat Diet Is Regulated by Nrf2 Through Multiple Pathways

10.21203/rs.3.rs-775710/v1 ◽

2021 ◽

Author(s):

sheng Qiu ◽

Zerong Liang ◽

Qinan Wu ◽

Miao Wang ◽

Mengliu Yang ◽

...

Keyword(s):

Lipid Metabolism ◽

Lipid Accumulation ◽

High Fat Diet ◽

Underlying Mechanism ◽

Luciferase Assay ◽

High Fat ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation

Abstract BackgroundNuclear factor erythroid 2-related factor 2 (Nrf2) is reportedly involved in hepatic lipid metabolism, but the results are contradictory and the underlying mechanism thus remains unclear. Herein we focused on elucidating the effects of Nrf2 on hepatic adipogenesis and on determining the possible underlying mechanism. We established a metabolic associated fatty liver disease (MAFLD) model in high fat diet (HFD) fed Nrf2 knockout (Nrf2 KO) mice; further, a cell model of lipid accumulation was established using mouse primary hepatocytes (MPHs) treated with free fatty acids (FAs). Using these models, we investigated the relationship between Nrf2 and autophagy and its role in the development of MAFLD.ResultsWe observed that Nrf2 expression levels were up-regulated in patients with MAFLD and diet-induced obese mice. Nrf2 deficiency led to hepatic lipid accumulation in vivo and in vitro, in addition to, promoting lipogenesis mainly by increasing SREBP-1 activity. Moreover, Nrf2 deficiency attenuated autophagic flux and inhibited the fusion of autophagosomes and lysosomes in vivo and in vitro. Weakened autophagy caused reduced lipolysis in the liver. Importantly, Chromatin immunoprecipitation-qPCR (ChIP-qPCR) and dual-luciferase assay results proved that Nrf2 bound to LAMP1 promoter and regulated its transcriptional activity. We accordingly report that Nrf2-LAMP1 interaction has an indispensable role in Nrf2-regulated hepatosteatosis. ConclusionsThese data collectively confirm that Nrf2 deficiency promotes hepatosteatosis by enhancing SREBP-1 activity and attenuating autophagy. To conclude, our data reveal a novel multi-pathway effect of Nrf2 on lipid metabolism in the liver, and we believe that multi-target intervention of Nrf2 signaling is a promising new strategy for the prevention and treatment of MAFLD.

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Antiobesity Effect of a Novel Herbal Formulation LI85008F in High-Fat Diet-Induced Obese Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6612996 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Hak Joo Choi ◽

Hwa Young Kim ◽

Kyoung Sik Park

Keyword(s):

Weight Gain ◽

Body Fat ◽

Fat Mass ◽

High Fat Diet ◽

Body Weight Gain ◽

Whole Body ◽

Body Fat Mass ◽

Obese Mice ◽

High Fat ◽

Herbal Formulation

A variety of natural products have been explored for their antiobesity potential and widely used to develop dietary supplements for the prevention of weight gain from excess body fat. In an attempt to find a natural antiobesity agent, this study was designed to evaluate the antiobesity activity of a novel herbal formulation LI85008F composed of extracts from three medicinal plants in high-fat diet- (HFD-) induced obese mice. After the thirteen-week oral administration of the test materials to mice, the body weight gain, whole-body fat mass, adipose tissue weight, and the expression levels of obesity-related proteins were measured. Our results indicated that LI85008F can suppress body weight gain and lower whole-body fat mass in HFD-induced obese mice. Significant decreases in epididymal and retroperitoneal fat mass were observed in LI85008F-treated groups compared with the HFD-fed control group ( p < 0.05 ). Furthermore, the oral administration of LI85008F caused significant decreases in the expression level of adipogenic (C/EBPα and PPARγ) and lipogenic (ACC) markers and notable increases in the production level of thermogenetic (AMPKα, PGC1α and UCP1) and lipolytic (HSL) proteins. These findings suggest that LI85008F holds great promise for a novel herbal formulation with antiobesity activities, preventing body fat accumulation and altering lipid metabolism.

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