Experimental study of Lentinan antagonizes against hepatic lipid deposition induced by sodium arsenite in mice / 公共卫生与预防医学

Objective To investigate the ameliorative effect of Lentinan (LNT) on sodium arsenite (SA)-induced hepatic lipid deposition in mice. Methods C57BL/6 mice were used as the experimental subjects, which were divided into control group, SA-exposed group, LNT + SA-exposed group and LNT control group. Blood and liver tissue samples were collected at the end of the experiment, and serum glutathione transaminase (ALT) and glutathione aminotransferase (AST) levels were detected by enzyme-linked immunosorbent assay (ELISA). A part of liver tissues was stained with hematoxylin-eosin (HE) or oil red O to observe the characteristics of liver pathological damage and lipid deposition, and another part of liver tissues was used to detect triglyceride (TG) and Adiponectin (APN) levels by ELISA. Results Compared with control group or LNT control group, SA-exposed group showed the increased levels of AST and ALT, showing the characteristics of liver histopathological damage and lipid deposition, and the APN level decreased while the TG level increased (P<0.05). Compared with SA-exposed group, the levels of AST and ALT decreased in LNT + SA-exposed group, showing the reduced degree of liver tissue damage and lipid deposition, and APN level upregulated while TG level downregulated (P<0.05). Conclusion Chronic SA exposure induces liver function damage, APN downregulation and lipid deposition in C57BL/6 mice, while LNT intervention leads to the significantly improvement of hepatic damage and lipid deposition, which may be related to the elevated APN level in liver.

Methyl ferulic acid ameliorates ethanol-induced L02 cell steatosis through microRNA-378b-mediated CaMKK2-AMPK pathway / 中国中药杂志

Alcoholic liver disease(ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Methyl ferulic acid(MFA) has been proven to significantly inhibit alcohol-induced lipid production in L02 cells through the AMP-activated protein kinase(AMPK) pathway, but its in-depth mechanism remains unclear. This study aimed to further clarify the mechanism of MFA in improving lipid accumulation in L02 cells through the microRNA-378b(miR-378b)-mediated calcium/calmodulin-dependent protein kinase kinase 2(CaMKK2)-AMPK signaling pathway based on existing researches. L02 cells were induced by 100 mmol·L~(-1) ethanol for 48 h to establish the model of ALD in vitro, and 100, 50, and 25 μmol·L~(-1) concentration of MFA was treated. MiR-378b plasmids(containing the overexpression plasmid-miR-378b mimics, silence plasmid-miR-378b inhibitor, and their respective negative control-miR-378b NCs) were transfected into L02 cells by electroporation to up-regulate or down-regulate the levels of miR-378b in L02 cells. The levels of total cholesterol(TC) and triglyceride(TG) in cells were detected by commercial diagnostic kits and automatic biochemical analyzers. The expression levels of miR-378b in L02 cells were detected by real-time quantitative polymerase chain reaction(qRT-PCR). CaMKK2 mRNA levels were detected by PCR, and protein expressions of related factors involved in lipid synthesis, decomposition, and transport in lipid metabolism were detected by Western blot. The results displayed that ethanol significantly increased TG and TC levels in L02 cells, while MFA decreased TG and TC levels. Ethanol up-regulated the miR-378b level, while MFA effectively inhibited the miR-378b level. The overexpression of miR-378b led to lipid accumulation in ethanol-induced L02 cells, while the silence of miR-378b improved the lipid deposition induced by ethanol. MFA activated the CaMKK2-AMPK signaling pathway by lowering miR-378b, thus improving lipid synthesis, decomposition, and transport, which improved lipid deposition in L02 cells. This study shows that MFA improves lipid deposition in L02 cells by regulating the CaMKK2-AMPK pathway through miR-378b.

Punicalagin inhibits hepatic lipid deposition in obese mice via AMPK/ACC pathway / 中国中药杂志

Hepatic lipid deposition is one of the basic manifestations of obesity, and nowadays pharmacological treatment is the most important tool. Punicalagin(PU), a polyphenol derived from pomegranate peel, is a potential anti-obesity substance. In this study, 60 C57BL/6J mice were randomly divided into a normal group and a model group. After establishing a model of simple obesity with a high-fat diet for 12 weeks, the successfully established rat models of obesity were then regrouped into a model group, an orlistat group, a PU low-dose group, a PU medium-dose group, and a PU high-dose group. The normal group was kept on routine diet and other groups continued to feed the high-fat diet. The body weight and food intake were measured and recorded weekly. After 8 weeks, the levels of the four lipids in the serum of each group of mice were determined by an automatic biochemical instrument. Oral glucose tole-rance and intraperitoneal insulin sensitivity were tested. Hemoxylin-eosin(HE) staining was applied to observe the hepatic and adipose tissues. The mRNA expression levels of peroxisome proliferators-activated receptor γ(PPARγ) and C/EBPα were determined by real-time quantitative polymerase chain reaction(Q-PCR), and the mRNA and protein expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), anterior cingulate cortex(ACC), and carnitine palmitoyltransferase 1A(CPT1A) were determined by Western blot. Finally, the body mass, Lee's index, serum total glyceride(TG), serum total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C) levels were significantly higher and high-density lipoprotein cholesterol(HDL-C) levels were significantly lower in the model group as compared with the normal group. The fat deposition in the liver was significantly increased. The mRNA expression levels of hepatic PPARγ and C/EBPα and the protein expression level of ACC were increased, while the mRNA and protein expression levels of CPT-1α(CPT1A) and AMPK were decreased. After PU treatment, the above indexes of obese mice were reversed. In conclusion, PU can decrease the body weight of obese mice and control their food intake. It also plays a role in the regulation of lipid metabolism and glycometabolism metabolism, which can significantly improve hepatic fat deposition. Mechanistically, PU may regulate liver lipid deposition in obese mice by down-regulating lipid synthesis and up-regulating lipolysis through activation of the AMPK/ACC pathway.

The impact of excessive gestational weight gain on fetal hepatic lipid metabolism and the regulatory mechanism / 中华实用儿科临床杂志

Objective:A rat model of excessive gestational weight gain (EGWG) was constructed to investigate the impact of EGWG on fetal hepatic lipid metabolism and the relevant regulatory mechanism.Methods:Healthy Sprague-Dawley rats were caged together and tested for pregnancy.Rats with the sperm observed under microscope were considered pregnant for 0.5 days.Pregnant rats were divided into the normal diet (ND) group and high-fat diet (HFD) group by the random number table method, with 8 rats in each group.The body weight during pregnancy of the pregnant rats was recorded.Cesarean section was performed at day 21.5 of gestation and the birth weight of the fetal rats was recorded.Hepatic lipid deposition of the pregnant and fetal rats was examined by hematoxylin-eosin (HE) staining and oil red O staining.Triglyceride (TG) and cholesterol (TC) levels in livers and serum of the pregnant and fetal rats were detected by glycerol phosphate oxidase-peroxidase(GPO-PAP) method.The mRNA and protein expression levels of key genes FASN and SREBP1c in hepatic lipid metabolism of fetal rats were measured by real-time polyme-rase chain reaction (RT-PCR) and Western blot.Differences between the two groups were compared by independent sample t test. Results:There was no difference in pre-pregnancy body weight between the HFD group and the ND group, but the differences in the weight and the weight gain during pregnancy gradually enlarged between the two groups.At day 21.5 of gestation, the weight of the pregnant rats[(467.75±22.05) g vs.(430.88±18.80) g, t=-3.600, P=0.003], the weight gain of the pregnant rats during pregnancy[(181.50±9.68) g vs.(148.50±10.86) g, t=-6.415, P<0.001] and the birth weight of the fetal rats[(5.51±0.17) g vs.(4.85±0.35) g, t=-4.779, P<0.001] of the HFD group were significantly higher than those of the ND group.Both HE staining and oil red O staining presented increased hepatic lipid deposition in the pregnant and fetal rats of the HFD group.The hepatic and serum TG and TC levels of the pregnant and fetal rats of the HFD group were significantly higher than those of the ND group (all P<0.05). RT-PCR and Western blot showed that the mRNA and protein levels of key genes FASN and SREBP1c in hepatic lipid metabolism of fetal rats of the HFD group were significantly higher than those of the ND group (all P<0.05). Conclusions:An EGWG model can be successfully constructed by a 21-day HFD during pregnancy.EGWG can lead to hepatic lipid deposition in the fetal rats.The mechanism may be related to the expression changes of key genes FASN and SREBP1c in hepatic lipid metabolism of fetal rats.

Dihydromyricin inhibited hepatic lipid deposition induced by high-fat diet in obese mice by activating SIRT1-AMPK pathway / 中国药理学通报

Aim To investigate the effect of dihydromyricetin (DHM) on lipid accumulation in liver of obese mice induced by high fat diet and its mechanism. Methods Sixty C57BL/6J mices were randomly divided into six groups (n = 10); (1)ND group; normal diet, (2)ND + L-DHM group; normal diet and treatment with low-dose DHM (125 mg • kg

Effect of Sulgidduk containing pine needle juice on lipid metabolism in high fat-cholesterol diet induced dyslipidemic rats / 한국영양학회지

PURPOSE: Dyslipidemia is a major risk factor for cardiovascular disease. Pine needles (Pinus densiflora seib et Zucc) are a traditional medicine used to treat dyslipidemia in clinical settings. This study examined the potential effects of sulgidduk, a Korean traditional rice cake containing pine needle juice to protect against dyslipidemia induced by a high-fat/sugidduk diet in a rat model. METHODS: Twenty one male Sprague-Dawley rats were divided randomly into three groups: normal control (NC), Sulgidduk diet (SD), Sulgidduk diet containing pine needle juice (PSD). The blood lipid levels, production of lipid peroxide in the plasma and liver, total cholesterol and triglyceride in the liver and feces, antioxidant enzyme activities in plasma and erythrocytes were measured to assess the effects of PSD on dyslipidemia. RESULTS: A high-fat/Sulgidduk diet induced dyslipidemia, which was characterized by significantly altered lipid profiles in the plasma and liver. The food intake was similar in the three groups, but weight gain and food efficiency ratio (FER) were reduced significantly in the PSD group compared to those in the SD group. The level of total cholesterol, LDL-cholesterol and TBARS in the plasma showed tendencies to decrease in the PSD group compared to those in the SD group. The levels of high-fat/Sulgidduk diet-induced sterol regulatory element-binding protein 2 (SREBP2) gene expression were reduced significantly in the PSD group. The supplementation of PSD reduced the hepatic triglyceride and total cholesterol levels significantly, and enhanced the fecal excretion of triglyceride and hepatic antioxidant enzyme activities compared to the SD group. CONCLUSION: These results suggest that the addition of 0.4% pine needle juice to Sulgidduk may be an alternative snack to control dyslipidemia.

New insight into inter-organ crosstalk contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver dysfunction and a significant global health problem with substantial rise in prevalence over the last decades. It is becoming increasingly clear that NALFD is not only predominantly a hepatic manifestation of metabolic syndrome, but also involves extra-hepatic organs and regulatory pathways. Therapeutic options are limited for the treatment of NAFLD. Accordingly, a better understanding of the pathogenesis of NAFLD is critical for gaining new insight into the regulatory network of NAFLD and for identifying new targets for the prevention and treatment of NAFLD. In this review, we emphasize on the current understanding of the inter-organ crosstalk between the liver and peripheral organs that contributing to the pathogenesis of NAFLD.

Helianthus tuberosus (Jerusalem artichoke) tubers improve glucose tolerance and hepatic lipid profile in rats fed a high-fat diet

Objectives To analyze the effects of feeding Helianthus tuberosus (HT) tubers on glucose tolerance and lipid profile in rats fed a high-fat diet (HFD). Methods A normal HFD or HFD including 10 w/w% HT tubers (HFD + HT) was fed to F334/Jcl rats. After 10 weeks, organ weights, glucose tolerance, and lipid profile were analyzed. Results The body weight, liver weight, and epidermal fat content in the HFD group were higher than those of the normal group, and similar to those of the HFD + HT group. The oral glucose tolerance test at 10 weeks revealed that the blood glucose level 30 min after beginning the test in the HFD + HT group was significantly lower than that in the HFD group. Liver triglyceride and total cholesterol levels in the HFD + HT group were significantly lower than those in the HFD group. Fecal triglyceride and total cholesterol levels in the HFD + HT group were higher than those in the HFD group. Histological analyses revealed that fat and glycogen accumulation increased in the HFD group, but decreased in the HFD + HT group. Conclusions These results indicate that HT tubers have anti-fatty liver effects based on improvements in glucose tolerance and the hepatic lipid profile.

Helianthus tuberosus (Jerusalem artichoke) tubers improve glucose tolerance and hepatic lipid profile in rats fed a high-fat diet

OBJECTIVES@#To analyze the effects of feeding Helianthus tuberosus (HT) tubers on glucose tolerance and lipid profile in rats fed a high-fat diet (HFD).@*METHODS@#A normal HFD or HFD including 10 w/w% HT tubers (HFD + HT) was fed to F334/Jcl rats. After 10 weeks, organ weights, glucose tolerance, and lipid profile were analyzed.@*RESULTS@#The body weight, liver weight, and epidermal fat content in the HFD group were higher than those of the normal group, and similar to those of the HFD + HT group. The oral glucose tolerance test at 10 weeks revealed that the blood glucose level 30 min after beginning the test in the HFD + HT group was significantly lower than that in the HFD group. Liver triglyceride and total cholesterol levels in the HFD + HT group were significantly lower than those in the HFD group. Fecal triglyceride and total cholesterol levels in the HFD + HT group were higher than those in the HFD group. Histological analyses revealed that fat and glycogen accumulation increased in the HFD group, but decreased in the HFD + HT group.@*CONCLUSIONS@#These results indicate that HT tubers have anti-fatty liver effects based on improvements in glucose tolerance and the hepatic lipid profile.

Progress in the programming effect of early nutrition on hepatic lipid metabolism / 国际儿科学杂志

The early life of nutrition is closely related to obesity and metabolic syndrome in adult.Lipid metabolic dysfunction is one of the important mechanisms in the development of adult diseases.Liver plays a key role in lipid metabolism.Hepatic lipid metabolism mainly includes fatty acid uptake,synthesis,esterification,oxidation and export.Exposed to a optimal nutrition environment in early life might lead to some adaptive effects in the liver and its organization structure,cell numbers and metabolic function.These adaptive responses might play a persistent effect in each way of hepatic lipid metabolism.Clarifying the programming effect of early nutrition on hepatic lipid metabolism and the relative molecular mechanism might provide related theoretical basis and practical molecular target for the prevention of adult diseases during childhood.

Desalinated underground seawater of Jeju Island (Korea) improves lipid metabolism in mice fed diets containing high fat and increases antioxidant potential in t-BHP treated HepG2 cells

This study was performed to investigate the effect of desalinated underground seawater (named as 'magma seawater', MSW) of Jeju Island in Korea on lipid metabolism and antioxidant activity. MSW was collected from underground of Han-Dong in Jeju Island, and freely given to high fat diet (HFD)-fed C57BL/6 mice for 10 weeks. Although there were no significant differences in the body weight changes and plasma lipid levels, hepatic triglyceride levels were significantly lower in the MSW group than in the normal tap water (TW)-drunken control group. Furthermore, the activity of fatty acid synthase (FAS) was significantly decreased and carnitine palmitoyltransferase (CPT) activity was increased in MSW group compared to TW group. Similarly, real-time PCR analysis revealed that mRNA expressions of lipogenic genes were lowered in MSW groups compared to the control group. In a morphometric observation on the liver tissue, accumulation of fats was remarkably reduced in MSW group. Meanwhile, in vitro assay, free radical scavenging activity measured by using diphenylpicrylhydrazyl (DPPH) was increased in MSW group. The 2'-7'-dichlorofluorescein diacetate (DCF-DA) staining followed with fluorescent microscopy showed a low intensity of fluorescence in MSW-treated HepG2 cells, compared to TW-treated HepG2 cells, which indicated that the production of reactive oxygen species by tert-butyl hydroperoxide (t-BHP) in HepG2 cells was decreased by MSW treatment. The antioxidant effect of MSW on t-BHP-induced oxidative stress in HepG2 cells was supported by the increased activities of intracellular antioxidant enzymes such as catalase and glutathione reductase. From these results, we speculate that MSW has an inhibitory effect on lipogenesis in liver and might play a protective role against cell damage by t-BHP-induced oxidative stress.

Effect of a Pholiota adiposa Extract on Fat Mass in Hyperlipidemic Mice

The purpose of this study was to investigate the effect of a Pholiota adiposa extract on fat mass in hyperlipidemic mice fed on a high-fat diet. The water extracts from P. adiposa (ASI 24018) were not affected in the total triglyceride contents and epididymal fat mass in mice fed on a high-fat diet, but the retroperitoneal fat mass decreased significantly. This result suggests that the P. adiposa extract may be a potential candidate for use as a functional food that can act as a prophylactic against hyperlipidemia. However, the P. adiposa extract showed no effect in the total triglyceride contents and epididymal fat mass.

EFFECTS OF DIETARY CHOLESTEROL ON LIPIDS METABOLISM IN RATS / 营养学报

Objective:To investigate the effect of dietary cholesterol on hepatic TG accumulation in rats. Method:Fourteen male Wistar rats were randomly divided into 2 groups and fed 1% cholesterol or cholesterol free AIN76 diets. After 4 w,serum triglyceride(TG) ,total cholesterol(TC) ,high density lipoprotein cholesterol(HDL-C) ,phospholipids(PL) ,glucose and free fatty acid(NEFA) levels were determined. Hepatic lipid concentrations(TG,TC,PL) and the activities and/or mRNA expression of malic enzyme(ME) ,glucose-6-phosphate dehydrogenase(G6PDH) ,fatty acid synthase(FAS) ,phosphatidate phophatase(PAP) ,carnitine palmitoyl transferase(CPT1,2) ,HMG-CoA reductase,acylCoA-cholesterol acyltransferase(ACAT) ,cholesterol 7?-hydroxylase(CYP7A) were also determined. Results:The serum TC and non-HDL-C levels were significantly increased but TG and HDL-C levels were significantly decreased by cholesterol feeding. The concentrations of hepatic TC and TG were 4-20 folds higher in cholesterol group than those in cholesterol free group. The activities of hepatic ME,G6PDH,FAS,PAP and CPT were depressed by cholesterol(40%,70%,50%,15% and 25% respectively) . The mRNA expression of FAS,CPT1,CPT2,and HMG-CoA reductase were down-regulated(35%,30%,50% and 25% respectively) and CYP7? and ACAT were up regulated(6.5 and 1.6 fold) by cholesterol in liver. Conclusion:The dietary cholesterol increases TG accumulation in liver,but dose not stimulates the activity and the gene expressionof hepatic TG synthesis related enzymes.