scholarly journals PEGylated Curcumin Derivative Attenuates Hepatic Steatosis via CREB/PPAR-γ/CD36 Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Liu ◽  
Fei Cheng ◽  
Yuxuan Luo ◽  
Zhu Zhan ◽  
Peng Hu ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Liver Lipid ◽  
Serum Triglyceride ◽  
The Body ◽  
Chow Diet ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Curcumin Derivative

Curcumin has the potential to cure dyslipidemia and nonalcoholic fatty liver disease (NAFLD). However, its therapeutic effects are curbed by poor bioavailability. Our previous work has shown that modification of curcumin with polyethylene glycol (PEG) improves blood concentration and tissue distribution. This study sought to investigate the role of a novel PEGylated curcumin derivative (Curc-mPEG454) in regulating hepatic lipid metabolism and to elucidate the underlying molecular mechanism in a high-fat-diet- (HFD-) fed C57BL/6J mouse model. Mice were fed either a control chow diet (D12450B), an HFD (D12492) as the NAFLD model, or an HFD with Curc-mPEG454 administered by intraperitoneal injection at 50 mg/kg or 100 mg/kg for 16 weeks. We found that Curc-mPEG454 significantly lowered the body weight and serum triglyceride (TG) levels and reduced liver lipid accumulation in HFD-induced NAFLD mice. It was also shown that Curc-mPEG454 suppressed the HFD-induced upregulated expression of CD36 and hepatic peroxisome proliferator activated receptor-γ (PPAR-γ), a positive regulator of CD36. Moreover, Curc-mPEG454 dramatically activated cAMP response element-binding (CREB) protein, which negatively controls hepatic PPAR-γ expression. These findings suggest that Curc-mPEG454 reverses HFD-induced hepatic steatosis via the activation of CREB inhibition of the hepatic PPAR-γ/CD36 pathway, which may be an effective therapeutic for high-fat-diet-induced NAFLD.

scholarly journals Paradoxical Protective Effect of Perfluorooctanesulfonic Acid Against High-Fat Diet–Induced Hepatic Steatosis in Mice

2018 ◽  
Vol 37 (5) ◽  
pp. 383-392 ◽  
Author(s):  
Ian Huck ◽  
Kevin Beggs ◽  
Udayan Apte
Keyword(s):  
Hepatic Steatosis ◽  
Lipid Content ◽  
High Fat Diet ◽  
Organic Pollutant ◽  
Dietary Lipid ◽  
Chow Diet ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Perfluorooctanesulfonic Acid

Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant with worldwide bioaccumulation due to a very long half-life. Perfluorooctanesulfonic acid exposure results in significant hepatic effects including steatosis, proliferation, hepatomegaly, and in rodents, carcinogenesis. The objective of this study was to determine whether PFOS exposure exacerbates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis pathogenesis. Eight-week-old male C57BL/6 J mice (n = 5 per group) were fed ad libitum normal chow diet (ND) alone, 60% high-fat diet (HFD) alone, ND + PFOS, and HFD + PFOS (0.0001% w/w (1 mg/kg) of PFOS) for 6 weeks. Both HFD alone and the ND + PFOS treatment induced significant adiposity and hepatomegaly, but the HFD + PFOS treatment showed a marked protection. Oil Red O staining and quantitative analysis of hepatic lipid content revealed increased hepatic steatosis in ND + PFOS and in HFD alone fed mice, which was prevented in HFD + PFOS treatment. Further studies revealed that ND + PFOS treatment significantly affected expression of lipid trafficking genes to favor steatosis, but these changes were absent in HFD + PFOS group. Specifically, expression of CD36, the major lipid importer in the cells, and peroxisome proliferator-activated receptor gamma (PPARγ), its major regulator, were induced in HFD + no treatment (NT) and ND + PFOS-fed mice but remained unchanged in HFD + PFOS mice. In conclusion, these data indicate that coadministration of PFOS with HFD mitigates steatosis and hepatomegaly induced by HFD and that by PFOS fed in ND diet via regulation of cellular lipid import machinery. These findings suggest dietary lipid content be considered when performing risk management of PFOS in humans and the elucidation of PFOS-induced hepatotoxicity.

Therapeutic effects of açaí seed extract on hepatic steatosis in high‐fat diet‐induced obesity in male mice: a comparative effect with rosuvastatin

2020 ◽  
Vol 72 (12) ◽  
pp. 1921-1932
Author(s):  
Thamires Barros Tavares ◽  
Izabelle Barcellos Santos ◽  
Graziele Freitas Bem ◽  
Dayane Teixeira Ognibene ◽  
Ana Paula Machado Rocha ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Seed Extract ◽  
Therapeutic Effects ◽  
Male Mice ◽  
High Fat ◽  
Comparative Effect ◽  
Diet Induced Obesity

scholarly journals The Effects of Triacylglycerol Structures on the Food Intake and Body Weight of Mice in a High-Fat Diet Setting

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1216-1216
Author(s):  
Xinge Hu
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
High Fat Diet ◽  
Tissue Sample ◽  
Body Weight Gain ◽  
Diet Group ◽  
The Body ◽  
Lower Percentage ◽  
Chow Diet ◽  
High Fat

Abstract Objectives The dietary fat content plays an important role in the regulation of chronic metabolic diseases such as obesity and type 2 diabetes. Here, we tested the impacts of triacylglycerol structure on the body weight gain and food intake of mice in a high-fat diet (HFD) setting. Methods Male C57/BL6J mice at 6 weeks old were fed one of the following three diets for 6 weeks, Teklad Rodent Diet chow diet (number 8640), the chow diet containing 36% (w/w) 1,2-Dipalmitoyl-3-oleoylglycerol (PPO), or the chow diet containing 36% (w/w) 1,3-Dipalmitoyl-2-oleoylglycerol (POP). Each group contained 9 mice, and their food intake and BW were measured daily. The mice were euthanized after 6 weeks (12 weeks old) for tissue sample collection. Results Both high HFD groups had significantly higher BW gain and caloric intakes than the chow diet group. Mice fed the POP diet had a lower percentage of BW gain and consumed less accumulated calories than those fed the PPO diet, as well as a significantly lower liver to BW ratio. Since week 4, the body BW rate of the POP group started to be lower than that of the PPO diet group. Conclusions TAG structures in an HFD setting affect the BW gain rate and obesity in mice. The different structures of fat added to affect the food intake and BW gain differently in an HFD setting. In the future, we would like to compare the changes of the hepatic lipogenesis enzyme in these mice. This will help us to understand how the triacylglycerol structures in the diet affect lipid metabolism in mice. Funding Sources Internal.

scholarly journals Anti-Obesity and Antidiabetic Effects of Nelumbinis Semen Powder in High-Fat Diet-Induced Obese C57BL/6 Mice

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3576
Author(s):  
Su Bin Hwang ◽  
Bog-Hieu Lee
Keyword(s):  
Protein Expression ◽  
High Fat Diet ◽  
Serum Triglyceride ◽  
Fold Increase ◽  
Normal Diet ◽  
The Body ◽  
Model Assessment ◽  
High Fat ◽  
Antidiabetic Effects ◽  
Nelumbinis Semen

Nelumbinis Semen (NS, the seeds of Nelumbo nucifera) extract is a traditional Korean medicine with anti-oxidant activity. The present study examined the anti-obesity and antidiabetic effects of NS powder in high-fat diet (HFD)-induced obese C57BL/6 mice. Mice (n = 8/group) were fed a normal diet (CON), HFD, HFD containing 5% NS powder (HFD-NS5%), or HFD containing 10% NS powder (HFD-NS10%) for 12 weeks. Food intake was relatively higher in groups HFD-NS5% and HFD-NS10%, while the food efficiency ratio was highest in group HFD (p < 0.05). HFD-NS5% reduced the body weight (−39.1%) and fat weight (−26.6%), including epididymal fat and perirenal fat, and lowered the serum triglyceride levels (−20.6%) compared with HFD. Groups HFD-NS5% and HFD-NS10% showed hepatoprotective properties, reducing the serum ALT levels (p < 0.05) and fat globules (size and number) in the liver compared with group HFD. HFD-NS5% and HFD-NS10% regulated the blood glucose, improved the glucose intolerance, and showed a 12.5% and 15.0% reduction in the area under the curve (AUC) of intraperitoneal glucose tolerance test (IPGTT), and a 26.8% and 47.3% improvement in homeostatic model assessment insulin resistance (HOMA-IR), respectively, compared with HFD (p < 0.05). Regarding the expressions of genes related to anti-obesity and antidiabetes, there was a 1.7- and 1.3-fold increase in PPAR-α protein expression, 1.4- and 1.6-fold increase in PPAR-γ protein expression, and 0.7- and 0.6-fold decrease in TNF-α protein expression, respectively, following HFD-NS5% and HFD-NS10% treatments, compared with HFD, and GLUT4 protein expression increased relative to CON (p < 0.05). These results comprehensively provide the fundamental data for NS powder’s functional and health-promoting benefits associated with anti-obesity and antidiabetes.

scholarly journals MEK6 Overexpression Exacerbates Fat Accumulation and Inflammatory Cytokines in High-Fat Diet-Induced Obesity

2021 ◽  
Vol 22 (24) ◽  
pp. 13559
Author(s):  
Suyeon Lee ◽  
Myoungsook Lee
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Liver Lipid ◽  
Mapk Signaling ◽  
Chow Diet ◽  
High Fat ◽  
Fat Accumulation ◽  
Diet Induced Obesity ◽  
Lipid Formation

Obesity is a state of abnormal fat accumulation caused by an energy imbalance potentially caused by changes in multiple factors. MEK6 engages in cell growth, such as inflammation and apoptosis, as one of the MAPK signaling pathways. The MEK6 gene was found to be related to RMR, a gene associated with obesity. Because only a few studies have investigated the correlation between MEK6 and obesity or the relevant mechanisms, we conducted an experiment using a TgMEK6 model with MEK6 overexpression with non-Tg and chow diet as the control to determine changes in lipid metabolism in plasma, liver, and adipose tissue after a 15-week high-fat diet (HFD). MEK6 overexpression in the TgMEK6 model significantly increased body weight and plasma triglyceride and total cholesterol levels. p38 activity declined in the liver and adipose tissues and lowered lipolysis, oxidation, and thermogenesis levels, contributing to decreased energy consumption. In the liver, lipid formation and accumulation increased, and in adipose, adipogenesis and hypertrophy increased. The adiponectin/leptin ratio significantly declined in plasma and adipose tissue of the TgMEK6 group following MEK6 expression and the HFD, indicating the role of MEK6 expression in adipokine regulation. Plasma and bone-marrow-derived macrophages (BMDM) of the TgMEK6 group increased MEK6 expression-dependent secretion of pro-inflammatory cytokines but decreased levels of anti-inflammatory cytokines, further exacerbating the results exhibited by the diet-induced obesity group. In conclusion, this study demonstrated the synergistic effect of MEK6 with HFD in fat accumulation by significantly inhibiting the mechanisms of lipolysis in the adipose and M2 associated cytokines secretion in the BMDM.

scholarly journals Extracts ofCoreopsis tinctoriaNutt. Flower Exhibit Antidiabetic Effects via the Inhibition ofα-Glucosidase Activity

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Wujie Cai ◽  
Lijing Yu ◽  
Yu Zhang ◽  
Li Feng ◽  
Siyuan Kong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Antioxidant Properties ◽  
Serum Triglyceride ◽  
Chow Diet ◽  
High Fat ◽  
Glucosidase Activity ◽  
Coreopsis Tinctoria

The aim of this study was to assay the effects ofCoreopsis tinctoriaNutt. flower extracts on hyperglycemia of diet-induced obese mice and the underlying mechanisms.Coreopsis tinctoriaflower was extracted with ethanol and water, respectively. The total phenol, flavonoid levels, and the constituents of the extracts were measured. For the animal experiments, C57BL/6 mice were fed with a chow diet, high-fat diet, or high-fat diet mixed with 0.4% (w/w) water and ethanol extracts ofCoreopsis tinctoriaflower for 8 weeks. The inhibitory effects of the extracts onα-glucosidase activity and the antioxidant properties were assayedin vitro. We found that the extracts blocked the increase of fasting blood glucose, serum triglyceride (TG), insulin, leptin, and liver lipid levels and prevented the development of glucose tolerance impairment and insulin resistance in the C57BL/6 mice induced by a high-fat diet. The extracts inhibitedα-glycosidase activity and increased oxidant activityin vitro. In conclusion,Coreopsis tinctoriaflower extracts may ameliorate high-fat diet-induced hyperglycemia and insulin resistance. The underling mechanism may be via the inhibition ofα-glucosidase activity. Our data indicate thatCoreopsis tinctoriaflower could be used as a beverage supplement and a potential source of drugs for treatment of diabetics.

scholarly journals Hypolipidemic Effects of Three Purgative Decoctions

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Sung-Hui Tseng ◽  
Ting-Yi Chien ◽  
Jiun-Rong Chen ◽  
I-Hsin Lin ◽  
Ching-Chiung Wang
Keyword(s):  
High Fat Diet ◽  
Weight Control ◽  
Internal Heat ◽  
Serum Triglyceride ◽  
Hepatic Function ◽  
The Body ◽  
Lipid Lowering ◽  
High Fat ◽  
Beneficial Effects ◽  
Lipid Lowering Effect

In traditional Chinese medicine (TCM), purgation is indicated when a person suffers an illness due to the accumulation of evil internal heat. Obese individuals with a large belly, red face, thick and yellow tongue fur, constipation, and avoidance of heat are thought accumulates of evil internal heat, and they are also treated with purgatives such asTa-Cheng-Chi-Tang(TCCT),Xiao-Chen-Chi-Tang(XCCT), andTiao-Wei-Chen-Chi-Tang(TWCCT) by TCM doctors. In previous studies, our group found that TCCT has potent anti-inflammatory activity, and that XCCT is an effective antioxidant. Since rhubarb is the principle herb in these three prescriptions, we will first present a thorough review of the literature on the demonstrated effect (or lack of effect) of rhubarb and rhubarb-containing polyherbal preparations on lipid and weight control. We will then continue our research with an investigation of the anti-obesity and lipid-lowering effect of TCCT, XCCT, TWCCT, and rhubarb extracts using two animal models. TWCCT lowered the serum triglyceride concentration as much as fenofibrate in Triton WR-1339-treated mice. Daily supplementation with XCCT and TWCCT significantly attenuated the high-fat-diet-induced hypercholesterolemia in rats. In addition, TWCCT also significantly lowered the high-fat-diet-induced hypertriglycemia. Although feeding high-fat diet rats with these extracts did not cause loose stools or diarrhea or other deleterious effects on renal or hepatic function. None of these extracts lowered the body weight of rats fed on high-fat diet. In conclusion, the results suggest that XCCT and TWCCT might exert beneficial effects in the treatment of hyperlipidemia.

scholarly journals Impact of High-Fat Diet in Early-Life on Mammary Metabolic and Inflammatory Status in Later-Life in Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 54-54
Author(s):  
Ying Tang ◽  
Ting-Chun Lin ◽  
Soonkyu Chung ◽  
Young-Cheul Kim ◽  
Zhenhua Liu
Keyword(s):  
Wnt Signaling ◽  
High Fat Diet ◽  
Early Life ◽  
Later Life ◽  
The Body ◽  
Chow Diet ◽  
High Fat ◽  
Inflammatory Status ◽  
Standard Chow Diet ◽  
Tnf Α

Abstract Objectives Emerging evidence indicates a potentially important role for early-life events and exposures in cancer development later in life. Moreover, accumulating evidence suggests that the incidence of cancers has reached a plateau in elders, whereas it continuously rises in young to middle adult. The present study aimed to investigate the potential impacts of high-fat diet in early-life, mimicking childhood/adolescent in humans, on mammary health in later-life of mice, equivalent to the young to middle age in human. Methods Female C57BL/8 mice (4 weeks of age) were fed a low-fat diet (LF: 10% kcal from fat) or a high-fat diet (HF: 60% kcal from fat) for 8 weeks, which is equivalent to child/adolescent age in humans. Mice in early-life groups were sacrificed after 8 weeks feeding, whereas mice in later-life groups were switched to standard chow diet (Lab Diet#5P76) and fed for additional 12 weeks before sacrifice. A panel of metabolic parameters, inflammatory cytokines, as well as gene expression related to tumorigenic Wnt-signaling were assessed by qPCR and immunoblotting analysis. Results Compared with LF group, the body weight in HF group was significantly elevated after 8-wk HF diet feeding (P &lt; 0.05). After switching to the standard chow diet for 12 weeks, the significance remained until 24 weeks of age although with a reduced degree of magnitude (P &lt; 0.05). For the metabolic factors, HFD reduced the expression levels of both Pparγ (P = 0.08) and adiponectin (P &lt; 0.05) at 12 weeks and the reductions remains at 24 weeks (P &lt; 0.01). Meanwhile, expressions of aromatase, estrogen receptor α and Tnf-α, Il-6, Il-10 as well as Cox2 among examined inflammatory mediators (Tnf-α, Il-6, Il-10, Il-2, Il-1β, Ifn-γ, Cox2) were significantly higher in HF than in LF group at 24 weeks (P &lt; 0.05). For Wnt-signaling target genes (Cyclin D1, C-Myc, and Axin 2), a significant increase for C-Myc was observed in HF group at 12 weeks (P &lt; 0.01). Conclusions Our results suggested that HF diet in early-life enhances adiposity and alters mammary metabolic and inflammatory status, creating a microenvironment in favor of breast tumorigenesis in later-life. Funding Sources This project was supported by USDA/Hatch (#1013548).

scholarly journals Dietary Polysaccharide from Enteromorpha clathrata Attenuates Obesity and Increases the Intestinal Abundance of Butyrate-producing Bacterium, Eubacterium xylanophilum, in Mice Fed a High-Fat Diet

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3286
Author(s):  
Jiali Wei ◽  
Yiran Zhao ◽  
Chen Zhou ◽  
Qing Zhao ◽  
Hongqian Zhong ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
High Throughput Sequencing ◽  
Serum Levels ◽  
Bioinformatic Analysis ◽  
The Body ◽  
Therapeutic Effects ◽  
High Fat ◽  
Intestinal Dysbiosis ◽  
Treatment Of Obesity

Previous studies have suggested that polysaccharide from Enteromorpha clathrata (ECP) could be used as a potential prebiotic to treat dysbiosis-associated diseases. However, whether it has any therapeutic effects on obesity has not been investigated. In the present study, we explored the anti-obesity effect of ECP and illustrated that it can significantly reduce the body weight and decrease the serum levels of triacylglycerol and cholesterol in high-fat diet (HFD)-fed mice. As revealed by 16S rRNA high-throughput sequencing and bioinformatic analysis, HFD remarkably changed the composition of the gut microbiota and promoted the growth of opportunistic pathogens such as Mucispirillum, Desulfobacterota and Alphaproteobacteria in obese mice. Interestingly, ECP improved intestinal dysbiosis caused by HFD and reshaped the structure of the gut microbiota in diseased mice by increasing the abundance of butyrate-producing bacterium, Eubacterium xylanophilum, in the gut. Altogether, we demonstrate for the first time an anti-obesity effect of ECP and shed new light into its therapeutic mechanisms from the perspective of gut microbiota. Our study will pave the way for the development of ECP as new prebiotic for the treatment of obesity and its associated disorders.

scholarly journals Tetrahydroxanthohumol, a xanthohumol derivative, attenuates high-fat diet-induced hepatic steatosis by antagonizing PPARγ

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Zhang ◽  
Gerd Bobe ◽  
Cristobal L Miranda ◽  
Malcolm B Lowry ◽  
Victor L Hsu ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Caloric Intake ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Competitive Binding Assay ◽  
Docking Simulations ◽  
Synthetic Derivative

We previously reported xanthohumol (XN), and its synthetic derivative tetrahydro-XN (TXN), attenuates high-fat diet (HFD)-induced obesity and metabolic syndrome in C57Bl/6J mice. The objective of the current study was to determine the effect of XN and TXN on lipid accumulation in the liver. Non-supplemented mice were unable to adapt their caloric intake to 60% HFD, resulting in obesity and hepatic steatosis; however, TXN reduced weight gain and decreased hepatic steatosis. Liver transcriptomics indicated that TXN might antagonize lipogenic PPARγ actions in vivo. XN and TXN inhibited rosiglitazone-induced 3T3-L1 cell differentiation concomitant with decreased expression of lipogenesis-related genes. A peroxisome proliferator activated receptor gamma (PPARγ) competitive binding assay showed that XN and TXN bind to PPARγ with an IC50 similar to pioglitazone and 8–10 times stronger than oleate. Molecular docking simulations demonstrated that XN and TXN bind in the PPARγ ligand-binding domain pocket. Our findings are consistent with XN and TXN acting as antagonists of PPARγ.

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