scholarly journals 2,4-dinitrophenol downregulates genes for diabetes and fatty liver in obese mice

Author(s):  
Qian Gao ◽  
Jiang He ◽  
Tao Liao ◽  
Qing-Ping Zeng

Whether obesity is a disease or a risk factor of chronic diseases including diabetes and fatty liver remains debating. We report here that a high-fat diet (HFD) alone or HFD and intramuscular injection of mice with a high dose (1.2 mg/kg) of lipopolysaccharide (LPS) induces the peripheral noninflammatory obesity. In contrast, HFD and intraperitoneal injection of mice with a low dose (0.25 mg/kg) of LPS induces the visceral low-grade inflammatory obesity. While the noninsulin dependent diabetes mellitus (NIDDM)- and nonalcoholic fatty liver disease (NAFLD)-related genes are globally upregulated in HFD+low-dose LPS mice, NIDDM and NAFLD genes are not extensively upregulated in HFD+high-dose LPS mice. The mitochondrial uncoupler 2,4-dinitrophenol (DNP) was found to exert a weight-reducing effect in obese mice by downregulating NF-κB-primed inflammatory response accompanying with NIDDM and NAFLD genes, thereby abrogating inflammatory hepatic injury. In conclusion, visceral low-grade inflammatory obesity that predisposes NIDDM and NAFLD can be ameliorated by DNP via anti-inflammation.

2015 ◽  
Author(s):  
Qian Gao ◽  
Jiang He ◽  
Tao Liao ◽  
Qing-Ping Zeng

Whether obesity is a disease or a risk factor of chronic diseases including diabetes and fatty liver remains debating. We report here that a high-fat diet (HFD) alone or HFD and intramuscular injection of mice with a high dose (1.2 mg/kg) of lipopolysaccharide (LPS) induces the peripheral noninflammatory obesity. In contrast, HFD and intraperitoneal injection of mice with a low dose (0.25 mg/kg) of LPS induces the visceral low-grade inflammatory obesity. While the noninsulin dependent diabetes mellitus (NIDDM)- and nonalcoholic fatty liver disease (NAFLD)-related genes are globally upregulated in HFD+low-dose LPS mice, NIDDM and NAFLD genes are not extensively upregulated in HFD+high-dose LPS mice. The mitochondrial uncoupler 2,4-dinitrophenol (DNP) was found to exert a weight-reducing effect in obese mice by downregulating NF-κB-primed inflammatory response accompanying with NIDDM and NAFLD genes, thereby abrogating inflammatory hepatic injury. In conclusion, visceral low-grade inflammatory obesity that predisposes NIDDM and NAFLD can be ameliorated by DNP via anti-inflammation.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Ding Zheng ◽  
Mengyun Peng ◽  
Xiaoning Zhu ◽  
Jing Wang

The purpose of this study was to investigate the effect of Qutanhuoxue decoction on AQP7 and AQP9 expression in nonalcoholic fatty liver model rats. Nighty male SD rats (six weeks old, 250 ± 10 g) were randomly divided into 5 groups: normal diet group (ND group), high-fat diet (HFD group), HFD + low dose Qd group, HFD + middle dose Qd group, and HFD + high dose Qd group. Rats in ND group were fed with a regular diet, while rats in other groups were fed with high-fat diet. After the success of the molding, HFD + low dose Qd group, HFD + middle dose Qd group, and HFD + high dose Qd group were, respectively, gavaged by Qutanhuoxue decoction with concentration of 4.5g.kg−1.d−1, 9.0g.kg−1.d−1, and 18g.kg−1.d−1. The ND group and HFD group were gavaged by the same volume of physiological saline lavage, once a day. During the period of gavaging, the other four groups continue to be fed with high-fat fodder except ND group. All rats were killed at 14d, 21d, and 28d, respectively. HE staining was used to observe the pathological changes of liver tissues and serum level of ALT AST GGT and TC TG was detected by automatic analyzer. The expression levels of liver AQP9 mRNA and adipose tissue AQP7 mRNA were detected by real-time PCR. Quhuoxue decoction can significantly reduce the liver function (ALT, AST, and GGT) and blood fat (TG, TC) levels of NAFLD rats and reduce the degree of liver fat degeneration. The effect was the best in the HFD + high dose Qd group of 28d. Qutanhuoxue decoction can decrease the expression of liver AQP9 mRNA and increase the expression of adipose tissue AQP7 mRNA. In conclusion, Qutanhuoxue decoction can reduce the degree of hepatic steatosis, which may be closely related to the increase of AQP7 expression in adipose tissue and the decrease of AQP9 expression in liver.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2224
Author(s):  
Jen-Her Lu ◽  
Kai Hsia ◽  
Chih-Hsun Lin ◽  
Chien-Chin Chen ◽  
Hsin-Yu Yang ◽  
...  

Objective: Hazelnut oil (HO) is rich in monounsaturated fatty acids and polyunsaturated fatty acids. This study intended to analyze the effects of hazelnut oil supplementation on the serum lipid profile and nonalcoholic fatty liver disease in hamsters fed a high-cholesterol (HC) diet. Methods: Hamsters were fed a basic diet (control group) and an HC diet (HC group) for 16 weeks (n = 10 in each group). Hamsters were fed an HC diet for four weeks to induce hyperlipidemia and were then fed an HC diet enriched with 5% (low-dose HC + HO group; n = 10) and 10% HO (high-dose HC + HO group; n = 10) for 12 weeks. Serum lipid levels, hepatic changes (including steatosis, inflammation, and fibrosis), and hepatic prooxidant-antioxidant status (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST)) were evaluated after the treatment period. Results: Hamsters in the control group showed normal serum lipid profiles, normal liver function, and moderate glycogen storage without hepatic steatosis. Hamsters in the HC group showed severe hyperlipidemia, severe hepatic steatosis, and moderate steatohepatitis (mononuclear cell and neutrophil infiltration, oval cell hyperplasia, and fibrosis). Compared to the HC group, both the low-dose and the high-dose HC + HO groups showed a significant reduction of hyperlipidemia (serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein cholesterol (VLDL-C levels)) and improved liver function (serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT)). Additionally, compared to the HC group, intrahepatic triglyceride accumulation (IHTC) was significantly higher in the HC + HO group, while the incidence of steatohepatitis was significantly lower. The intake of the HC diet was associated with a higher level of lipid peroxidation (malondialdehyde, MDA) and a lower concentration of hepatic antioxidant enzymes (SOD, GPx, and GST), and all these factors were partially improved in the low-dose and high-dose HC + HO groups. Conclusions: Our findings indicate that the intake of HO reduced serum hyperlipidemia and oxidative stress and ameliorated the progression of nonalcoholic fatty liver disease in hamsters fed a high-cholesterol diet.


2017 ◽  
Vol 82 (7) ◽  
pp. 1765-1774 ◽  
Author(s):  
Jae Hwan Kim ◽  
Sujin Suk ◽  
Woo Jung Jang ◽  
Chang Hyung Lee ◽  
Jong-Eun Kim ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Hyun-Young Na ◽  
Mi Hyeon Seol ◽  
Mia Kim ◽  
Byung-Cheol Lee

Background. This study was performed to evaluate the effect of Seyoeum (SYE), a novel herbal meal replacement, on insulin resistance and nonalcoholic fatty liver disease (NAFLD) in obese mice fed with a high-fat diet (HFD).Methods. SYE contained six kinds of herbal powder such asCoix lacryma-jobi,Oryza sativa,Sesamum indicum,Glycine max,Liriope platyphylla,andDioscorea batatas. Male C57BL/6 mice were divided into four groups: normal chow (NC), HFD, SYE, and HFD plus SYE (HFD + SYE). The mice in groups other than NC were fed HFD for 9 weeks to induce obesity and then were fed each diet for 6 weeks. Clinical markers related to obesity, diabetes, and NAFLD were examined and gene expressions related to inflammation and insulin receptor were determined.Results. Compared with HFD group, body weight, serum glucose, serum insulin, HOMA-IR, total cholesterol, triglyceride, epididymal fat pad weight, liver weight, and inflammatory gene expression were significantly reduced in SYE group. Insulin receptor gene expression increased in SYE group.Conclusions. Based on these results, we conclude that SYE improved obesity and insulin resistance in high-fat fed obese mice. Our findings suggest that SYE could be a beneficial meal replacement through these antiobesity and anti-insulin resistance effects.


2020 ◽  
Author(s):  
Yu-Chun Lin ◽  
Hsiu-Chen Huang ◽  
Yu-Heng Lai ◽  
Jui-Chieh Chen ◽  
Hsiao-Hsuan Tien ◽  
...  

Abstract Background Obesity and its associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are a particular worldwide health problem at present. Momordica cochinchinensis fruit is consumed widely in Southeast Asia. However, whether it has functional effects on fat-induced metabolic dysfunction and gut microbiota remains unclear. This study was conducted to determine how Momordica cochinchinensis aril (MCA) affects obesity, nonalcoholic fatty liver, insulin resistance and gut microbiota in diet-induced obese mice.Methods Wild type male mice at age of 5 weeks received four different kinds of diets: a normal diet, high-fat diet (HFD), or HFD supplemented with 1% or 3% (wt:wt) lyophilized MCA for 10 weeks. Body weight, adipose tissue and liver weight, serum biochemical parameters, glucose tolerance and liver lipids were measured. Gut microbial composition was analyzed.Results MCA protected the mice against high-fat diet (HFD)-induced body weight gain, hyperlipidemia and hyperglycemia, compared with mice that were not treated. MCA inhibited the expansion of adipose tissue and adipocyte hypertrophy. In addition, the insulin sensitivity-associated index that evaluates insulin function was also significantly restored. MCA also regulated the secretion of adipokines in HFD-induced obese mice. Moreover, hepatic fat accumulation and liver inflammation were reduced, which suggested that fatty liver was prevented by MCA. Furthermore, MCA supplementation suppressed hepatic lipid accumulation by activation of AMPK and PPAR-alpha signaling pathway in the human fatty liver HuS-E/2 cell model. Supplementation with MCA resulted in microbiota populations changed significantly.Conclusion Our data indicate that dietary MCA is involved in the prevention of HFD-induced adiposity, insulin resistance and nonalcoholic fatty liver disease and altered the microbial contents of the gut and modulated microbial dysbiosis in the host.


2018 ◽  
Vol 17 (4) ◽  
pp. 415-421
Author(s):  
Li Li ◽  
Wang Huali ◽  
Ai Min ◽  
Pan Jian

The objective of this study was to examine the effect of grape pomace extracts on obesity-induced nonalcoholic fatty liver disease (NAFLD) in rats. To this end, forty male Wistar rats were assigned into four groups and were fed regular chow, high-fat diet, high-fat diet plus low-dose grape pomace extract (0.5%, w/w) or high-dose (2%, w/w) grape pomace extract (GPE) for 16 weeks. We observed that lipid concentrations (triglyceride and cholesterol) were elevated in the plasma and liver in rats on a high-fat diet and also on those receiving 2% GPE with high-fat diet. These changes were resulting from the downregulation of lipogenic enzymes and stimulation of hepatic lipolysis. A high-fat diet-mediated increase in hepatic oxidative stress was reduced by GPE. The plasma levels of proinflammatory cytokines TNF-α and IL-6 were significantly decreased by GPE. These results suggest that the supplementation with GPE may ameliorate adiposity, hepatic steatosis, oxidative stress and inflammation in high-fat diet-fed rats and potentially retard the development of obesity-induced NAFLD.


2016 ◽  
Vol 44 (03) ◽  
pp. 551-564 ◽  
Author(s):  
Mingxing Yang ◽  
Xiumin Li ◽  
Xin Zeng ◽  
Zhimin Ou ◽  
Mei Xue ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disorder characterized by the accumulation of excess fat in the liver. Rheum palmatumL. (RP) decoctions have been reported to ameliorate NAFLD. The aim of the present study was to investigate the effects and underlying mechanisms of RP in fatty liver disease induced by a high-fat diet (HFD) in rats. Low and high doses of aqueous RP extraction were orally administered to HFD-fed rats for six weeks. Body weight, tissue weight, glucose tolerance, insulin tolerance, hepatic morphology, and liver triglyceride (TG) content were assessed. The effects of RP on the expressions of lipogenic and lipolysis genes were measured by quantitative real-time PCR. The phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) was determined by Western blotting. Treatment with low-dose RP significantly reduced liver weight, liver TG content, and improved glucose tolerance in HFD-fed rats. Consistently, RP attenuated excess fat accumulation and downregulated the expression of lipogenic genes in the liver. Further, an increased phosphorylation of AMPK and ACC was observed. These findings suggest that low-dose RP alleviates hepatosteatosis, at least in part, by stimulating AMPK activity.


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