Lipid Accumulation In Liver Tissue Research Articles

C-C chemokine receptor type 5 deficiency exacerbates alcoholic fatty liver disease through pro-inflammatory cytokines and chemokines-induced hepatic inflammation.

Chemokines and chemokine receptors implicated with alcoholic liver disease. Studies have shown that inflammation and oxidative stress induce fat molecules aggregation in liver. We evaluated the relationship between alcoholic fatty liver disease and C-C chemokine receptor 5 (CCR5) and impact of inflammation and oxidative stress in fat molecule deposition. Lieber-DeCarli diet containing ethanol or isocaloric control diets were fed to wild-type and CCR5 knockout mice for 10days and gavaged with a single dose of ethanol or isocaloric maltose dextrin at 11th day. Cytokine, chemokine, and reactive oxygen species levels were measured in liver tissues to study the role of CCR5 in alcoholic fatty liver disease. C-C chemokine receptor type 5 knockout mice exacerbated ethanol-induced liver injury. Serum levels of aspartate aminotransferase and alanine aminotransferase were higher in CCR5 knockout mice than wild-type mice, and CCR5 knockout mice showed more severe lipid accumulation in liver tissue than wild-type mice after ethanol feeding. Increased expressions of pro-inflammatory cytokines TNF-α and IL-6 and chemokines CCL2, CCL3, CCL4, and CCL5 result in exacerbation of hepatitis in CCR5 knockout mice after ethanol feeding. Oxidative stress induced by reactive oxygen species was more severe in CCR5 knockout mice, and increasing level of fatty acid import and decreasing level of lipid degradation resulted in lipid accumulation in ethanol-fed CCR5 knockout mice. Deficiency of CCR5 exacerbates alcoholic fatty liver disease by hepatic inflammation induced by pro-inflammatory cytokines and chemokines and oxidative stress.

Theophylline-Based KMUP-1 Improves Steatohepatitis via MMP-9/IL-10 and Lipolysis via HSL/p-HSL in Obese Mice.

KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) has been reported to cause hepatic fat loss. However, the action mechanisms of KMUP-1 in obesity-induced steatohepatitis remains unclear. This study elucidated the steatohepatitis via matrix metallopeptidase 9 (MMP-9) and tumor necrosis factor α (TNFα), and related lipolysis via hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) by KMUP-1. KMUP-1 on steatohepatitis-associated HSL/p-HSL/ATGL/MMP-9/TNFα/interleukin-10 (IL-10) and infiltration of M1/M2 macrophages in obese mice were examined. KMUP-1 was administered by oral gavage from weeks 1–14 in high-fat diet (HFD)-supplemented C57BL/6J male mice (protection group) and from weeks 8–14, for 6 weeks, in HFD-induced obese mice (treatment group). Immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining of tissues, oil globules number and size, infiltration and switching of M1/M2 macrophages were measured to determine the effects on livers. IL-10 and MMP-9 proteins were explored to determine the effects of KMUP-1 on M1/M2 macrophage polarization in HFD-induced steatohepatitis. Long-term administration of KMUP-1 reversed HFD-fed mice increased in body weight, sGOT/sGPT, triglyceride (TG) and glucose. Additionally, KMUP-1 decreased MMP-9 and reactive oxygen species (ROS), and increased HSL/p-HSL and IL-10 in HFD mice livers. In conclusion, KMUP-1, a phosphodiesterase inhibitor (PDEI), was shown to reduce lipid accumulation in liver tissues, suggesting that it could be able to prevent or treat steatohepatitis induced by HFD.

金錢草 추출물이 고지방 식이에 의한 생쥐의 지질 대사 변화에 미치는 영향

Objectives : Herba on lipid levels in serum and lipid accumulation in liver tissue in high fat diet-induced hyperlipidemic mice. Methods : Experimental groups were subdivided into four; Normal diet group (Nor), Hyperlipidemic mice (Con), Lysimachiae Herba water extract administered mice (LWE), Lysimachiae Herba methanol extract administered mice (LME). Thereafter the changes in body weight, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, AST, ALT, fasting blood glucose in serum were measured. In addition histopathological changes in liver tissue was also observed. Results : Body weight, AST and ALT were not affected by the administration of water or methanol extracts of Lysimachiae Herba. However, methanol extracts of Lysimachiae Herba down regulated the total cholesterol and triglyceride in high fat diet - induced hyperlipidemic mice. Conclusions : In this study, results of total cholesterol and triglyceride showed significant effect in LME compared with LWE, but other results didn’t. Therefore, it is necessary to have more study of Lysimachiae Herba to apply hyperlipidemia.

Elastin Insufficiency Predisposes Mice to Impaired Glucose Metabolism.

Williams-Beuren syndrome is the consequence of a large contiguous-gene deletion on the seventh human chromosome that includes the elastin gene. Elastin is an extracellular matrix protein responsible for the cardiovascular abnormalities associated with Williams’s syndrome, including hypertension and aortic stenosis. A high percentage of individuals with Williams’s syndrome also have impaired glucose tolerance, independent of traditional risk factors for diabetes. Here, we show that murine adipose tissue does assemble elastic fibers; however, isolated elastin insufficiency (Eln+/−) in mice does not independently influence glucose metabolism or tissue lipid accumulation. Similarly, isolated ApoE deficiency (ApoE−/−), a model of hyperlipidemia and atherosclerosis, does not impair insulin sensitivity. However, Eln+/−; ApoE−/− double mutant mice exhibit notable hyperglycemia, adipocyte hypertrophy, inflammation of adipose tissue, and ectopic lipid accumulation in liver tissue. Further, Eln+/−; ApoE−/− mutants have significant impairment of insulin sensitivity by insulin tolerance testing, independent of body weight or diet, suggesting that elastin insufficiency predisposes to metabolic disease in susceptible individuals.

Deep Sea Water Modulates Blood Pressure and Exhibits Hypolipidemic Effects via the AMPK-ACC Pathway: An in Vivo Study

Deep sea water (DSW), originally pumped from the Pacific Rim off the coast of Hualien County (Taiwan), and its mineral constituents, were concentrated by a low-temperature vacuum evaporation system to produce a hardness of approximately 400,000 mg/L of seawater mineral concentrate. The primary composition of this seawater mineral concentrate was ionic magnesium (Mg2+), which was approximately 96,000 mg/L. Referring to the human recommended daily allowance (RDA) of magnesium, we diluted the mineral concentrate to three different dosages: 0.1 × DSW (equivalent to 3.75 mg Mg2+/kg DSW); 1 × DSW (equivalent to 37.5 mg Mg2+/kg DSW); and 2 × DSW (equivalent to 75 mg Mg2+/kg DSW). Additionally, a magnesium chloride treatment was conducted for comparison with the DSW supplement. The study indicated that 0.1 × DSW, 1 × DSW and 2 × DSW decreased the systolic and diastolic pressures in spontaneous hypertensive rats in an eight-week experiment. DSW has been shown to reduce serum lipids and prevent atherogenesis in a hypercholesterolemic rabbit model. Our results demonstrated that 1 × DSW and 2 × DSW significantly suppressed the serum cholesterol levels, reduced the lipid accumulation in liver tissues, and limited aortic fatty streaks. These findings indicated that the antiatherogenic effects of DSW are associated with 5′-adenosine monophosphate-activated protein kinase (AMPK) stimulation and the consequent inhibition of phosphorylation of acetyl-CoA carboxylase (ACC) in atherosclerotic rabbits. We hypothesize that DSW could potentially be used as drinking water because it modulates blood pressure, reduces lipids, and prevents atherogenesis.

통심락(通心絡)이 고지방식이로 유도된 이상지질혈증 생쥐의 체내 지질 변화에 미치는 영향

Objectives : This study was designed to investigate the effects of Tong Xin Lou (TXL) on lipid accumulation in liver tissue in Hypercholesterolemic mice. TXL is new drug, which is one of Cardiotonic Pills. TXL is used for activating the blood flow in the restoration stage of cerebral infarction, and for alleviation of angina pectoris including the symptoms as chest oppressed and stabbing pain. Methods : Hyperlipidemia was induced by providing high fat diet for 6 weeks. Normal group was provided with normal rodent diet. TXL was administered orally in the concentration of 10 mg/day for 2 weeks (TXL group). D/W was administered orally in CTL group for 2 weeks. We observed histopathological changes in liver and heart tissues, and also investigated the effect on body weights, and levels of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride in serum. Results : In this study, TXL did not affects weight gain in hypercholesterolemic mice. TXL group showed downward tendency of lipid accumulation compared with CTL group. In addition, oral administration of TXL lowered levels of total cholesterol (P < 0.05) and triglyceride (P < 0.05), which were elevated by induction of hypercholesterolemia. Conclusion : These results suggest that TXL can prevent lipid accumulation in liver tissue through regulation of dyslipidemia.

Ethanolic Extract ofVitis thunbergiiExhibits Lipid Lowering Properties via Modulation of the AMPK-ACC Pathway in Hypercholesterolemic Rabbits

Vitis thunbergii (VT) is a wild grape that has been shown to provide various cardioprotective effects. The present study was designed to examine whether a VT extract could reduce serum lipid levels and prevent atherogenesis in a hypercholesterolemic rabbit model. At the end of an 8-week study, our results showed that a VT extract supplement markedly suppressed the serum levels of cholesterol and low-density lipoprotein, reduced lipid accumulation in liver tissues, and limited aortic fatty streaks. Our findings suggest that the VT extract activated AMPK (5′-adenosine monophosphate-activated protein kinase) with subsequent inhibition of the activation of ACC (acetyl-CoA carboxylase). Our results suggest that this VT extract could be further developed as a potential lipid-lowering agent and as a natural health food to prevent atherogenesis.

Effects on Body Mass of Laboratory Rats after Ingestion of Drinking Water with Sucrose, Fructose, Aspartame, and Sucralose Additives~!2009-03-31~!2010-11-25~!2010-08-26~!

The excessive consumption of natural sweeteners is considered to be a major cause of increase in body mass. The authors wished to establish whether hypocaloric artificial sweeteners also promoted mass gain in laboratory rats (Harlan Wistar male rats). Ad libitum sweeteners were added to the drinking water of five groups of nine male rats each weighing circa 40g: Group 1, 15% fructose; group 2, 10% sucrose; group 3, 0.3% aspartame; group 4, 0.19% sucralose; and group 5 (control), ordinary drinking water. The daily volume of water consumption, the amount of ingested food, and gain of body mass were assessed during 73 days. Histological sections of the liver tissue of these rats were analyzed using Sudan and Hematoxylin-Eosin red staining. Results indicated that the fructose solution promoted the highest final gain in body mass, statistically different from the control and sucrose groups (p<0.05). The caloric consumption was similar to that of the sucrose group, but different from that of the control and one of the groups consuming hypocaloric sweeteners, aspartame (p<0.05). Rats that ingested sucrose solutions had the lowest final body mass in spite of the fact that their total caloric intake was one of the highest, and as mentioned, similar to fructose. Rats that drank water with hypo-caloric artificial sweeteners, aspartame and sucralose ingested the same amount of food, and the caloric intake was similar to the control group (p<0.05). They were fatter than the control and sucrose groups, although their caloric consumption was lower than that of the fructose-drinking specimens, apparently confirming recent findings about glucose absorption with ingestion of artificial sweeteners. The behavior of the sucralose group, with a body mass higher than those of the control and sucrose groups, should be further studied, since this group showed a tendency to drink more water over time when compared to the control and aspartame groups. Liver-to-body mass ratios were not statistically different (p<0.05) among the five groups, but both groups consuming hypocaloric sweeteners had slightly lower ratios than the sucrose, fructose, and control groups. As has been mentioned in previous research, ingestion of fructose solutions led to an increase of lipids in the liver tissue, in comparison with the other groups studied. Groups consuming hypocaloric sweeteners also showed a slight increase in lipid accumulation in liver tissue but not as much as the fructose-consuming group. The results of these experiments indicate the advisability of a long term experiment focusing on the ingestion of these sweeteners and their role in the increase in body mass.

Liver autofluorescence properties in animal model under altered nutritional conditions

Autofluorescence spectroscopy is a promising and powerful approach for an in vivo, real time characterization of liver functional properties. In this work, preliminary results on the dependence of liver autofluorescence parameters on the nutritional status are reported, with particular attention to vitamin A and lipid accumulation in liver tissue. Normally fed and 24 h starving rats were used as animal models. Histochemical and autofluorescence analysis showed that lipids and vitamin A colocalize in the liver parenchyma. Fasting condition results in a parallel increase in both lipids and vitamin A. Autofluorescence imaging and microspectrofluorometric analysis carried out on unfixed, unstained tissue sections under 366 nm excitation, evidenced differences in both spectral shape and response to continuous irradiation between liver biopsies from fed and starving rats. As to photobleaching, in particular, fitting analysis evidenced a reduction of about 85% of the signal attributable solely to vitamin A during the first 10 s of irradiation. The tissue whole emission measured in fed and starving rat livers exhibited reductions of about 35% and 52%, respectively, that are closely related to vitamin A contents. The findings open interesting perspectives for the set up of an in situ, real time diagnostic procedure for the assessment of liver lipid accumulation, exploiting the photophysical properties of vitamin A.

Peripartal Metabolism and Production of Holstein Cows Fed Diets Supplemented with Fat During the Dry Period

Previous research from our laboratory demonstrated that cows fed supplemental fat throughout the dry period in an attempt to increase body condition score (BCS) had little hepatic lipid accumulation at d 1 postpartum compared with cows fed an isocaloric high-grain diet or a lower energy control diet. However, results were confounded by lower dry matter intake and loss of BCS by cows fed the fat-supplemented diet. Here, cows were fed a control diet (C) moderately high in nonfiber carbohydrates (NFC) or an isocaloric fat-supplemented, low NFC (F) diet to reassess the effects of supplemental fat throughout the dry period on peripartal lipid accumulation in liver. A more energy-dense, high-NFC diet supplemented with fat (CF) was also fed to test the efficacy of supplemental fat in a diet with similar carbohydrate composition but higher energy density. Intakes of dry matter and net energy for lactation were similar among treatments throughout the experiment, although diet×day interactions during the last 21 d before parturition indicated that cows fed CF decreased intakes more slowly. Cows gained similar amounts of BCS and body weight among diets prepartum, but cows fed C tended to lose more BCS and body weight around parturition. Milk production and milk components did not differ among treatments. Prepartum concentrations of glucose, insulin, total protein, nonesterified fatty acids, and μ-hydroxybutyrate in plasma were similar among treatments. Supplemental fat increased prepartum concentrations of urea and cholesterol in plasma. Postpartum concentrations of metabolites and insulin in plasma were similar among treatments. Concentrations of total lipid and triglyceride in liver increased at parturition, whereas hepatic glycogen concentration decreased, but concentrations were not different among treatments. Supplemental fat fed prepartum did not affect peripartal lipid accumulation in liver tissue and did not benefit postpartum milk production.