scholarly journals Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Huanhuan Feng ◽  
Lili Yu ◽  
Guojun Zhang ◽  
Guoyan Liu ◽  
Can Yang ◽  
...  

High mobility group box 1 protein (HMGB1) is a molecule related to the development of inflammation. Autophagy is vital to maintain cellular homeostasis and protect against inflammation of adipocyte injury. Our recent work focused on the relationship of HMGB1 and autophagy in 3T3-L1 cells. In vivo experimental results showed that, compared with the normal-diet group, the high-fat diet mice displayed an increase in adipocyte size in the epididymal adipose tissues. The expression levels of HMGB1 and LC3II also increased in epididymal adipose tissues in high-fat diet group compared to the normal-diet mice. The in vitro results indicated that HMGB1 protein treatment increased LC3II formation in 3T3-L1 preadipocytes in contrast to that in the control group. Furthermore, LC3II formation was inhibited through HMGB1 knockdown by siRNA. Treatment with the HMGB1 protein enhanced LC3II expression after 2 and 4 days but decreased the expression after 8 and 10 days among various differentiation stages of adipocytes. By contrast, FABP4 expression decreased on the fourth day and increased on the eighth day. Hence, the HMGB1 protein modulated autophagy-related proteins and lipid-metabolism-related genes in adipocytes and could be a new target for treatment of obesity and related metabolic diseases.

2020 ◽  
Author(s):  
Yuan Yang ◽  
Feng Zhang ◽  
Xiao Xiao ◽  
Chunlian Ma ◽  
Hua Liu ◽  
...  

AbstractOur aims were to explore the effects of dietary and behavior interventions on lipometabolism caused by unhealthy high-fat diet and the best method to rebuild lipid homeostasis of this lifestyle. Apart from normal diet rats, 34 rats were fed with high-fat emulsion for 4 weeks before being divided into 4 groups and intervened for another 4 weeks. 8 of them were classified into high-fat control group and 9 were sorted into high-fat diet with rice vinegar group. Meanwhile, 10 were put into high-fat diet with swimming group and 7 were just for refeeding normal diet group. Then the data of body weight was recorded and analyzed. Serum, pancreas, liver, cardiac tissues and epididymis adipose were sampled as required. Indexes of serum were tested by kits. AMPKα, HNF1α, CTRP6 from tissues were detected by western blot. According to our experiments, Swimming and refeeding groups reflected a better regulation on lipid homeostasis mainly by up-regulating the expression of pancreas AMPKα. To be more specific, the refeeding rats showed lower T-CHO (P<0.001) and LDL-C (P<0.05), but higher weight gain (P<0.001),insulin level (P<0.01)and pancreas AMPKα (P<0.01)than high-fat control rats. Compared with rats experimented by swimming or rice vinegar, they showed higher weight gain (P<0.001),insulin level (P<0.01)and HNF1α, but lower of CTRP6. In summary, refeeding diet functioned better in regulating the lipometabolic level after high-fat diet. Whatever approach mentioned above we adopted to intervene, the best policy to keep the balance of lipid homeostasis is to maintain a healthy diet.


Author(s):  
Pipit Pitriani ◽  
◽  
Wang-Lok Lee ◽  
Hee-Geun Park ◽  
◽  
...  

The incidence of obesity has been spreading throughout the world. Many of the complications caused by obesity, such as inflammation and impaired liver function. This study aimed to determine the effect of supplementation resveratrol and chrysin on inflammation and liver function of obese mice fed a high-fat diet. 40 mice (C57BL/6) were randomly divided into four groups: 10 in the normal diet (NC), 10 control group on a high-fat diet (HC), 10 in the high-fat diet with resveratrol (HRE), and 10 in the high-fat diet group with chrysin (HCH). Resveratrol 25 mg and 50mg of chrysin supplement per kg body weight were orally given with 0.1ml solution of Dimethyl Sulfoxide (DMSO) dissolved in for 15 weeks (4 times/week). The calorie intake of the group supplemented by resveratrol and chrysin significantly decreased. Group with high-fat diet, resveratrol, and chrysin increased body weight significantly compared to the normal diet group. The liver weight decreased in the resveratrol but not in the chrysin group. TNFα did not decrease in the resveratrol and chrysin group while IL1β significantly decreased. TLR 4 significantly decreased only in the chrysin group, while IL10 only increased in the resveratrol group. The collagen was decreased by resveratrol and chrysin supplementation while fibronectin was not affected by resveratrol or chrysin. The inflammatory process in the liver of obese mice fed a high-fat diet can be reduced by supplementing resveratrol and chrysin.


2021 ◽  
Vol 22 (9) ◽  
pp. 4444
Author(s):  
Miey Park ◽  
Eun-Jung Park ◽  
So-Hyeun Kim ◽  
Hae-Jeung Lee

Obesity has become a worldwide health problem, and many significant inflammatory markers have been associated with the risk of side effects of obesity and obesity-related diseases. After a normal diet or high-fat diet with high-fructose water (HFHF) for 8 weeks, male Wistar rats were divided randomly into four experimental groups according to body weight. Next, for 8 weeks, a normal diet, HFHF diet, and HFHF diet with L. plantarum strains ATG-K2 or ATG-K6 were administered orally. Compared to the control group, the HFHF diet group showed significantly increased visceral fat, epididymal fat, and liver weight. The mRNA and protein expression levels of FAS and SREBP-1c were higher in the HFHF diet group than in the HFHF diet with L. plantarum strains ATG-K2 and ATG-K6. The HFHF diet with L. plantarum strain ATG-K2 showed significantly decreased inflammatory cytokine expression in the serum and small intestine compared to the HFHF diet group. Furthermore, histological morphology showed minor cell injury, less severe infiltration, and longer villi height in the small intestine ileum of the HFHF diet with L. plantarum strains groups than in the HFHF diet group. These results suggest that L. plantarum strains K2 and K6 may help reduce intestinal inflammation and could be used as treatment alternatives for intestinal inflammatory reactions and obesity.


Author(s):  
Rizka Veni ◽  
Awal Prasetyo ◽  
Muflihatul Muniroh

This study aims to analyze the effect of combination of motor vehicle particular matter exposure and high-fat diet in kidney histopathology, creatinine levels, and MDA levels in Wistar rats. This study used a posttest-only control group design. Eighteen healthy male Wistar rats were divided into three groups. The intervention groups received motor vehicle fume exposure for 100 s with normal diet (X1) or high-fat diet (X2), and the control group received no exposure (C). Data analysis was processed with a SPSS 25.0 computer program by using the one-way ANOVA test followed by post hoc LSD. The degree of kidney histopathological damage showed significant differences between the X1 and X2 groups when compared with the control group (p < 0.05). The results of the creatinine level examination found a significant difference between the X2 and C groups (p < 0.05) and the treatment groups X1 and X2 (p < 0.05). The results of kidney MDA level examination showed a significant difference between the treatment groups (X1 and X2) and the control group (p < 0.05). The combination of particular matter of motor vehicle fumes exposure and high-fat diet could induce kidney damage through histopathological change and increased creatinine levels and kidney MDA levels in Wistar rats.


2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Qishu Zhou ◽  
Chunyu Liang ◽  
Yafei Li ◽  
Yi Yan

Objective  To investigate the effect of one-time high-intensity intermittent exercise in white fat autophagy in obese rats and provide a theoretical basis of the molecular mechanism of exercise fat loss. Methods  Eighteen male 3-weeks-old rats were selected and divided into control group fed with normal diet (C), high-fat diet group fed with high fat diet (H). After 16 weeks, there were twelve obesity rats that divided into diet group (HS) and exercise group (HE). The other six control group rats of 19 weeks age were used as the standard (CS group). OE group did the high intensity intermittent exercise once. The CS group and the CS group were kept quietly. Three groups were taken subcutaneous white adipose tissue(S) and epididymal white adipose tissue (E) immediately after exercise. Mensurate the expression of LC3 gene in the tissue using the fluorescent quantitative PCR. Results 1. The expression of LC3 mRNA from white fat tissue was different to the tissues, which the expression of epididymal white adipose tissue of each group was higher than that in subcutaneous white adipose tissue (P <0.01). 2. Compared with CS group, the expression of epididymal white fat adipose tissue LC3 mRNA decreased (P<0.01) and the expression of the subcutaneous white adipose tissue increased from HS group (P <0.05). 3. Compared with OS group, the expression of epididymal white fat adipose tissue LC3 mRNA decreased (P<0.05) and the expression of subcutaneous white adipose tissue decreased from OS group. Conclusions The expression of LC3mRNA in epididymal white fat adipose tissue of rats was significantly higher than that of subcutaneous white fat. The changes of LC3mRNA expression of adipose tissue caused by high-fat diet have tissue differences. One-time high-intensity intermittent exercise can reduce the expression of LC3mRNA in fat tissue of obese rats. Its regulatory mechanism needs to be further studied.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Dale E Mais ◽  
Thomas Vihtelic ◽  
Chidozie Amuzie ◽  
Steven Denham ◽  
John R Swart ◽  
...  

Small animal models of atherosclerosis are commonly used in drug studies; however, the results often fail to translate into the clinic. A large animal model that more accurately reflects the human disease is needed. We recently developed a transgenic Yucatan pig model in which the LDL receptor (LDLR) gene is knocked out. Five groups of Yucatan pigs (N=4 per group), either wild type (LDLR+/+) or heterozygote (LDLR+/-) were fed a normal diet or a high fat diet for a six month period. One of the heterozygote/high fat diet groups in addition received a daily dose of a statin (atorvastatin) at 3 mg/kg. Every two weeks during the study a variety of clinical chemistry parameters were measured. At study termination, select arteries were collected, stained for lipid deposits and quantitated. In addition, sections of these arteries were prepared for immunohistochemistry to detect selected markers of macrophage infiltration into the atherosclerotic plaques. As expected, pigs fed a high fat diet gained significantly more weight at six months whether they were wild type or LDLR+/-. Atorvastatin appeared to attenuate this weight gain. There were significant increases in total cholesterol, HDL and LDL in pigs fed the high fat diet compared to their corresponding control group. The group receiving the atorvastatin had reduced values of these parameters compared to controls showing that a statin had a beneficial effect on lipid levels even in a high fat diet scenario. VLDL levels were not affected but there were triglyceride changes across the groups. Liver function was unchanged based on total bilirubin and AST while ALT measurements were altered in some of the groups. Immunohistochemistry and histomorphometry was performed on some arteries. Atorvastatin-induced amelioration of hypercholesterolemia in this model underscores its translational utility.


2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Minjie Lin ◽  
Jungke Long ◽  
Wenbo Li ◽  
Chenxuan Yang ◽  
Patricia Loughran ◽  
...  

Abstract Background Circulating high-mobility group box 1 (HMGB1) plays important roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Intracellular HMGB1 is critical for the biology of hepatocytes. However, the intracellular role of HMGB1 in hepatocellular steatosis is unknown. Therefore, we aimed to investigate the role of hepatocyte-specific HMGB1 (HC-HMGB1) in development of hepatic steatosis. Methods Wild type (WT) C57BL/6 and HC-HMGB1−/− mice were fed high-fat diet (HFD) or low-fat diet (LFD) for up to 16 weeks. Results As expected, HMGB1 translocated from nuclear into cytoplasm and released into circulation after HFD treatment. HC-HMGB1 deficiency significantly reduced circulating HMGB1, suggesting that hepatocyte is a major source of circulating HMGB1 during NAFLD. Unexpectedly, HC-HMGB1 deficiency promoted rapid weight gain with enhanced hepatic fat deposition compared with WT at as early as 4 weeks after HFD treatment. Furthermore, there was no difference between WT and HC-HMGB1−/− mice in glucose tolerance, energy expenditure, liver damage or systemic inflammation. Interestingly, hepatic gene expression related to free fatty acid (FFA) β-oxidation was significantly down-regulated in HC-HMGB1−/− mice compared with WT, and endoplasmic reticulum (ER) stress markers were significantly higher in livers of HC-HMGB1−/− mice. In vitro experiments using primary mouse hepatocytes showed absence of HMGB1 increased FFA-induced intracellular lipid accumulation, accompanied by increased ER-stress, significant downregulation of FFA β-oxidation, and reduced oxidative phosphorylation. Conclusions Our findings suggest that hepatocyte HMGB1 protects against dysregulated lipid metabolism via maintenance of β-oxidation and prevention of ER stress. This represents a novel mechanism for HMGB1-regulation of hepatocellular steatosis, and suggests that stabilizing HMGB1 in hepatocytes may be effective strategies for prevention and treatment of NAFLD.


2019 ◽  
Vol 97 (7) ◽  
pp. 611-622 ◽  
Author(s):  
Mohammed M. Heikal ◽  
Ahmed A. Shaaban ◽  
Wagdi F. Elkashef ◽  
Tarek M. Ibrahim

Febuxostat, a highly potent xanthine oxidase inhibitor with an antioxidant effect, inhibits elevated xanthine oxidase, leading to reduction of reactive oxygen species and oxidative stress, the main causes of vascular inflammation in hyperlipidemia. The aim of this study was to test the potential antioxidant and anti-inflammatory effects of febuxostat and (or) stopping a high-fat diet on the biochemical parameters in rabbits with hyperlipidemia induced by a high-fat diet. Male New Zealand rabbits were distributed into 3 groups: a normal control group fed standard chow for 12 weeks and 2 other groups fed a high-fat diet with 1% cholesterol for 8 weeks, and then shifted to standard chow for 4 weeks. During the last 4 weeks, one high-fat diet group received 0.5% carboxymethyl cellulose, whereas the other group was treated with febuxostat (2 mg/kg per day p.o.). Febuxostat significantly lowered low-density lipoprotein cholesterol (“bad” cholesterol) compared to the untreated group (high-fat diet group). Febuxostat also displayed a potent anti-inflammatory and antioxidant activity by decreasing serum levels of lipid peroxidation index, proinflammatory cytokines, and enhancing antioxidant enzyme activity. Stopping the hyperlipidemic diet in the high-fat diet group did not show improvement. These findings indicate the antioxidant and anti-inflammatory effects of febuxostat that may be common mechanisms of the anti-hyperlipidemic effect of this drug. Stopping a hyperlipidemic diet without treatment is not sufficient once injury has occurred.


2017 ◽  
Vol 49 (10) ◽  
pp. 793-800 ◽  
Author(s):  
Guoqiang Fan ◽  
Yu Qiao ◽  
Shixing Gao ◽  
Jun Guo ◽  
Ruqian Zhao ◽  
...  

AbstractZinc alpha2 glycoprotein (ZAG) is a new type of adipokine involved in adipose tissue mobilization, however, little is known about its lipid metabolism effect in liver. Therefore, we investigated the effects of ZAG in the regulation of hepatic lipid accumulation. Mice were randomly divided into two groups; one was fed a normal diet and another was fed a high-fat diet for eight weeks to establish obesity model. After that, the normal diet group was divided into ND (injection of pcDNA3.1) and NDZ (injection of ZAG recombinant plasmid) and the high-fat diet group was divided into HF (injection of pcDNA3.1) and HFZ (injection of ZAG recombinant plasmid). The mice were weighed once per week and injected with plasmid once every three days for eight times. The results showed that body weight and hepatic TG content were decreased dramatically in HFZ group compared with HF group. The stearoyl-CoAdesaturase1 (SCD1) and Acyl-CoA Synthetase-1 (ACSS1) protein levels in HFZ group were significantly decreased. Furthermore, phosphorylated hormone sensitive lipase (P-HSL) was significantly higher in HFZ group. In HFZ group, hepatic fatty acid translocase (CD36) and fatty acids binding protein-1 (FABP1) protein levels were reduced. In addition, the expression of phosphorylated protein kinase A (PPKA) in HFZ group was higher than the HF group. Meanwhile, NDZ group showed significantly decreased body weight and increased P-HSL level though the hepatic TG content showed no significantly changes compared with the ND group. Therefore, we conclude that ZAG may be beneficial for preventing high-fat-diet-induced hepatic lipid metabolic disorders.


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