Liver Cholesterol Concentrations Research Articles

Metabolic Effects of Short-Term High-Fat Intake Vary Depending on Dietary Amino Acid Composition

BackgroundIt is generally accepted that excessive fat intake has undesirable effects on the energy metabolism of our body. Dietary amino acid composition is also critical to the regulation of lipid metabolism. ObjectivesThis study aimed to investigate whether high-fat diets (HFDs) with different amino acid deficiencies lead to different metabolic outcomes. MethodsSix-wk-old male Wistar rats were fed either a control diet (CN; 3.7 kcal/g, 12% calories from fat) or HFDs (5.1 kcal/g, 60% calories from fat) with 7 different amino acid compositions [control or methionine, arginine, histidine, lysine, threonine, or branched-chain amino acids (BCAAs) deficient], for 7 d. Tissue weights and lipid accumulation in the liver, skeletal muscle, and adipose tissue were measured, and serum biochemical parameters were analyzed. ResultsAlthough the food intake of the HFD groups was a little less than that of the CN group, the total calorie intakes were comparable among the groups, except for histidine-deficient and BCAA-deficient groups. In rats fed am HFD with a control amino acid composition (HFCN), dramatic increase in triglyceride (TG) accumulation in the liver and serum LDL cholesterol concentration were observed compared with the CN group. However, when the arginine content in the diet was reduced, liver TG accumulation was completely inhibited, with no apparent effects on serum lipoprotein-cholesterol concentrations. Meanwhile, deficiency of the other amino acids, such as threonine, reversed HFD-induced upregulation of serum LDL cholesterol. ConclusionsIt is observed that although the rats ingested an excessive amount of fat, neither ectopic fat accumulation nor dyslipidemia were always induced at least in the short term; hence, the consequent metabolic change was dependent on the dietary amino acid composition. These findings introduce an important perspective regarding HFD regimens in both scientific and clinical contexts.

Deletion of Elovl5 leads to dyslipidemia and atherosclerosis in LDLR-deficient mice

Atherosclerosis is a chronic inflammatory disease for which hepatic steatosis and atherogenic dyslipidemia are significant risk factors. We investigated the effects of endogenously generated very-long-chain polyunsaturated fatty acids (VL-PUFAs) on dyslipidemia and atherosclerosis development using mice that lack ELOVL5, a PUFA elongase that is required for the synthesis of arachidonic acid, EPA, and DHA from the essential fatty acids linoleic and linolenic acids, and the LDL receptor (LDLR). Elovl5−/−;Ldlr−/− mice manifest increased liver triglyceride and cholesterol concentrations due to the activation of sterol regulatory element binding protein-1, a transcription factor that activates enzymes required for de novo lipogenesis. Plasma levels of triglycerides and cholesterol in VLDL, IDL, and LDL were markedly elevated in Elovl5−/−;Ldlr−/− mice fed a chow and the mice exhibited marked aortic atherosclerotic plaques. Bone marrow-derived monocytes from wild-type (WT) and Elovl5−/− mice were polarized to M1 and M2 macrophages, and the effects of ELOVL5 on inflammatory activity were determined. There were no differences in most of the markers tested for M1 and M2 polarized cells between WT and Elovl5−/− cells, except for a slight increase in PGE2 secretion in Elovl5−/− cells, likely due to elevated Cox-2 expression. These results suggest that the deletion of Elovl5 leads to hepatic steatosis and dyslipidemia, which are the major factors in severe atherosclerosis in Elovl5−/−;Ldlr−/− mice.

Effects of Full-Spectrum Cannabis Oil with a Cannabidiol:Tetrahydrocannabinol 2:1 Ratio on the Mechanisms Involved in Hepatic Steatosis and Oxidative Stress in Rats Fed a Sucrose-Rich Diet

Introduction: This study aimed to analyze the effects of cannabis oil (cannabidiol:tetrahydrocannabinol [CBD:THC], 2:1 ratio) on the mechanisms involved in hepatic steatosis and oxidative stress in an experimental model of metabolic syndrome (MS) induced by a sucrose-rich diet (SRD). We hypothesized that noninvasive oral cannabis oil administration improves hepatic steatosis through a lower activity of lipogenic enzymes and an increase in carnitine palmitoyltransferase-1 (CPT-1) enzyme activity involved in the mitochondrial oxidation of fatty acids. Furthermore, cannabis oil ameliorates liver oxidative stress through the regulation of the main regulatory factors involved, nuclear factor erythroid 2 (NrF2) and nuclear factor-kB (NF-κB) p65. For testing this hypothesize, a relevant experimental model of MS was induced by feeding rats with a SRD for 3 weeks. Methods: Male Wistar rats were fed the following diets for 3 weeks: reference diet: standard commercial laboratory diet, SRD, and SRD + cannabis oil: noninvasive oral administration of 1 mg/kg body weight cannabis oil daily. The full-spectrum cannabis oil presents a total cannabinoid CBD:THC 2:1 ratio. Serum glucose, triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (AP), N-arachidonoylethanolamine or anandamide and 2-arachidonoylglycerol endocannabinoids levels, thiobarbituric acid reactive substance (TBARS) levels, and non-enzymatic antioxidant capacity (ferric ion-reducing antioxidant power [FRAP]) were evaluated. In the liver tissue: histology, nonalcoholic fatty liver disease activity score (NAS), triglycerides and cholesterol content, lipogenic enzyme activities (fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, and glucose-6-phosphate dehydrogenase), enzyme related to mitochondrial fatty acid oxidation (CPT-1), reactive oxygen species, TBARS, FRAP, glutathione, catalase, glutathione peroxidase, and glutathione reductase enzyme activities. 4-hydroxynonenal, NrF2, and NF-κB p65 levels were analyzed by immunohistochemistry. Results: The results showed that SRD-fed rats developed dyslipidemia, liver damage, hepatic steatosis (increase of key enzymes related to the novo fatty acid synthesis and decrease of key enzyme related to mitochondrial fatty acid oxidation), lipid peroxidation, and oxidative stress. Hepatic NrF2 expression was significantly decreased and NF-κB p65 expression was increased. Cannabis oil administration improved dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation (improving enzymes involved in lipid metabolism), and oxidative stress. In the liver tissue, NrF2 expression increased, and NF-κB p65 expression was reduced. Conclusion: The present study revealed new aspects of liver damage and steatosis, lipid peroxidation, and oxidative stress in dyslipidemic insulin-resistant SRD-fed rats. We demonstrated new properties and molecular mechanisms of cannabis oil (CBD:THC, 2:1 ratio) on lipotoxicity and hepatic oxidative stress in an experimental model of MS.

Ellagic acid reduces hepatic lipid contents through regulation of SIRT1 and AMPK in old rats

Objective Ellagic acid is used in traditional medicine for the treatment of lipid disorders. In this study, the effects of ellagic acid on key regulators of lipid metabolism, and histopathological alterations in aged liver were examined. Methods A total of 21 male Wistar rats were divided into three groups, including young control, old control, and old ellagic acid. After one month of treatment with ellagic acid, the expression levels of hepatic SIRT1, AMPK, SREBP-1c, PPAR-α, and phosphorylated AMPK (p-AMPK) were evaluated. The levels of several serum biochemical factors, and hepatic triglyceride, and cholesterol contents were assessed. Results Ellagic acid elevated the levels of SIRT1, p-AMPK, and PPAR-α and reduced SREBP-1c level in the liver of old rats. It decreased triglyceride and cholesterol contents in the aged liver and improved histopathological changes. Conclusions The results demonstrated that ellagic acid can exert protective effects against hepatic lipid metabolism disorders induced by ageing.

Effect of Sub-Lethal, Carbaryl and Cartap Exposures on Lipid and Cholesterol Contents in Liver, Kidney and Gills of Channa Punctatus (BLOCH)

Channa punctatus were exposed for 24, 48, 72 and 96 h to sub-lethal concentration (30% of LC50 for 96h) of carbaryl and cartap (carbamate pesticides) in order to record their effect on total lipid and cholesterol contents in liver, kidney and gills. The normal lipid content in liver, kidney and gills ranged from 17.95±0.41 to18.21±0.38 mg/g, 15.55i-0.51 to16.21±0.35 mg/g and 8.53±0.39 to 9.58±0.33 mg/g, whereas cholesterol contents varied between 3.60±0.06 to 3.81±0.04 mg/g, 1.61±0.05 to 1.72±0.02 mg/g and 0.71±0.02 to 0.77±0.10 mg/g, respectively. The treatment elicited significant decline in lipid and cholesterol contents throughout the exposure period suggesting response of the fish to the pesticide intoxication.

Supranutrition of microalgal docosahexaenoic acid and calcidiol improved growth performance, tissue lipid profiles, and tibia characteristics of broiler chickens

BackgroundDocosahexaenoic acid (DHA) and calcidiol could be enriched in chicken for improving public nutrition and health. It remains unclear if supranutritional levels of DHA and calcidiol impair growth performance or metabolism of broiler chickens. This study was to determine singular and combined effects of high levels of supplemental DHA-rich microalgal biomass or oil and calcidiol on growth performance, concentrations of triglycerides, cholesterol, and nonesterfied fatty acids in plasma, liver, breast, and thigh, and biophysical properties of tibia.MethodsIn Exp. 1, 144 day-old Cornish chicks were divided into 4 groups (6 cages/treatment, 6 birds/cage), and were fed a corn-soybean meal basal diet (BD), BD + 10,000 IU calcidiol/kg (BD + Cal), BD + 1% DHA-rich Aurantiochytrium (1.2 g DHA/kg; BD + DHA), and BD + Cal + DHA for 6 weeks. In Exp. 2, 180 day-old chicks were divided into 5 groups, and were fed: BD, BD + DHA (0.33% to 0.66% oil, 1.5 to 3.0 g DHA/kg), BD + DHA + EPA (1.9% to 3.8% eicosapentaenoic acid-rich Nannochloropsis sp. CO18, 0.3 to 0.6 g EPA/kg), BD + DHA + calcidiol (6000 to 12,000 IU/kg diet), and BD + DHA + EPA + Cal for 6 weeks.ResultsBirds fed BD + Cal diet in Exp. 1 and BD + DHA + EPA diet in Exp. 2 had higher (P < 0.05) body weight gain (10%–11%) and gain:feed ratio (7%), and lower (P < 0.05) total cholesterol and triglyceride concentrations in plasma (18%–54%), liver (8%–26%), breast (19%–26%), and thigh (10%–19%), respectively, over the controls. The two diets also improved (P < 0.05) tibial breaking strength (8%–24%), total bone volume (2%–13%), and (or) bone mineral density (3%–19%) of chickens.ConclusionSupranutrition of dietary calcidiol and DHA alone or together did not produce adverse effects, but led to moderate improvements of growth performance, lipid profiles of plasma and muscle, and bone properties of broiler chickens.

Feeding Australian Acacia Gums and Gum Arabic Leads to Non-Starch Polysaccharide Accumulation in the Cecum of Rats

Exudative gums from two Australian Acacia species (A. pycnantha and A. baileyana) and gum arabic (from A. senegal) were fed to rats at graded levels (0, 20, 40, 80 g/kg), replacing cellulose in purified diets containing cholesterol plus cholic acid. Compared with consumption of the control diet containing cellulose only, consumption of the gums had no significant effects on concentrations of plasma or liver cholesterol. Plasma triacylglycerol concentrations were higher in rats fed gum arabic, whereas liver triacylglycerols were lower in rats fed the gums. The gums did not affect the total pool of volatile fatty acids in the ceca, as compared with results in controls, but did promote the relative contribution of propionate at the expense of acetate. In rats fed the diet containing cellulose (80 g/kg) the proportions of cecal acetate:propionate:butyrate were 76:15:9, whereas in the rats fed A. pycnantha gum, gum arabic and A. baileyana gum (80 g/kg) the ratios were 42:54:4, 35:46:19 and 43:53:4, respectively. The low apparent fermentability of the gums was confirmed by the accumulation of non-starch polysaccharides in cecal digesta. In rats fed 80 g/kg A. pycnantha gum, 3.44 g of soluble non-starch polysaccharides was measured in the ceca, which was 58% of the dry weight of the cecal contents. We conclude that the biological activities of the Australian Acacia gums were similar to those of gum arabic and that these gums may have potential value as human food ingredients.

Plasma Total and Lipoprotein Cholesterol, Liver Cholesterol and Fecal Cholesterol Excretion in Hamsters Fed Fiber Diets

The effect of dietary fibers on plasma lipids, liver cholesterol and fecal cholesterol excretion was investigated in hamsters. Male 9- to 11-wk-old Golden-Syrian hamsters (n = 155) were fed a purified hypercholesterolemic diet (0.1% cholesterol, 10% fat) for 5 wk to elevate plasma lipid concentrations. Sixteen animals with elevated plasma total cholesterol were randomly assigned to each treatment group: control, oat bran, guar gum, cellulose, xylan and terminal groups. After 4 wk of fiber diet consumption, the plasma total cholesterol concentrations were significantly decreased in the oat bran, guar gum and xylan groups (16, 12 and 15%, respectively) (P < 0.05). Plasma HDL cholesterol concentration was significantly decreased only in the guar gum group (12%) (P < 0.05). The combined plasma VLDL+LDL cholesterol concentrations were significantly lowered by the oat bran, xylan and cellulose diets (38, 34 and 40%, respectively) (P < 0.05). After 4 wk of control diet consumption, the liver cholesterol concentration quadrupled to 10.6 mumol cholesterol/g liver (P < 0.05). After 4 wk of consumption of the treatment diets, liver cholesterol was further increased (P < 0.05) only in the cellulose group, to 14.5 mumol cholesterol/g liver. The total fecal cholesterol excretion was the highest (P < 0.05) in the oat bran group. In the present study, oat bran, guar gum and xylan were effective hypocholesterolemic agents in hamsters.

Pectin Feeding Influences Fecal Bile Acid Excretion, Hepatic Bile Acid and Cholesterol Synthesis and Serum Cholesterol in Rats

This study was designed to investigate the effects of pectin on cholesterol and bile acid metabolism and to elucidate the mechanisms involved in its hypolipidemic effect in rats. The key regulatory enzymes in cholesterol and bile acid metabolism, 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and cholesterol 7α-hydroxylase, were determined. Circulating, hepatic, and biliary lipid concentrations and fecal bile acid excretion were also measured. Male Wistar rats were fed a fiber-free or a pectin-supplemented (7 g/100 g) diet for 4 wk. Bile flow and the biliary secretion of both bile acids and cholesterol were not significantly different than controls in pectin-fed rats. The addition of pectin to the diet resulted in lower serum and liver cholesterol concentrations (-27 and -17%, respectively). Fecal bile acid excretion (+168%) and the hepatic activity of cholesterol 7α-hydroxylase (+70%) were significantly higher in pectin-fed animals. HMG-CoA reductase activity was also significantly greater (+11%) in the presence of dietary pectin. Results of our study indicate that pectin, by enhancing fecal bile acid excretion, may cause increased hepatic synthesis of bile acids and liver depletion of cholesterol in rats, which results in a higher rate of cholesterol synthesis and reduced serum cholesterol concentrations.

Corn Silk Extract: A Potential Modulator for Producing Functional Low Cholesterol Chicken Eggs

The chicken egg is one of the most globally-consumed animal protein sources with high-quality protein value. However, there is a growing concern about the association between excessive egg consumption and the increasing risk of cardiovascular disease incidence. Meanwhile, corn silk extract (CSE) is known to have hypo-lipidemic bioactive properties, as well as antioxidant and anti-inflammatory effects. Thus, the present study was designed to investigate the effect of feeding laying hens three different CSE levels on egg cholesterol content as well as egg production performance and oxidative stress marker levels. A total of 240, 40-week-old, Hy-Line Brown laying hens were divided into 4 symmetric groups (10 hens × 6 replicates). The control group was fed a basal diet while the other three groups were given the basal diet supplemented with 100 mg, 200 mg, or 400 mg CSE per kg feed, respectively. Egg production performance was monitored for eight successive weeks. Internal and external egg quality parameters were also measured. At the end of week 48 of age, blood samples were collected to determine the plasma lipid profile, stress markers, and liver function indicators. Data revealed that supplementation of 200 mg and 400 mg CSE to laying hen diets had a positive effect on egg production performance with a significant increase in egg numbers and egg weight as well as significantly improved feed efficiency. Egg quality parameters were significantly improved with CSE supplementation. Lipid peroxidation levels and inflammation marker concentrations significantly decreased for the experimental groups that were fed 200 mg and 400 mg CSE compared with the control group. Meanwhile, blood total cholesterol decreased significantly with CSE supplementation, along with an increase in high-density and a decrease in low-density lipoprotein cholesterol content. A high positive correlation was found between liver and egg cholesterol contents (r = 0.902, p &lt; 0.0001) which was linearly decreased with the increasing level of CSE supplementation. Egg cholesterol content significantly decreased by 9 to 19% in the CSE-supplemented groups compared with the control group. The present study demonstrated that CSE at 100 mg/kg and up to 400 mg/kg diets can be safely used to improve laying hen egg production performance with a direct effect on lowering egg cholesterol content as well as improving the redox status.

Bacillus coagulans XY2 ameliorates copper-induced toxicity by bioadsorption, gut microbiota and lipid metabolism regulation

Excessive copper pollutes the environment and endangers human health, attracting plenty of global attention. In this study, a novel strain named Bacillus coagulans XY2 was discovered to have a great copper tolerance and adsorption capacity. B. coagulans XY2 might maintain copper homeostasis through multisystem synergies of copper resistance, sulfur metabolism, Fe-S cluster assembly, and siderophore transport. In mice, by promoting the expression of SREBF-1 and SREBF-2 and their downstream genes, B. coagulans XY2 significantly inhibited the copper-induced decrease in weight growth rate, ameliorated dyslipidemia, restored total cholesterol and triglyceride contents both in serum and liver. Furthermore, B. coagulans XY2 recovered the diversity of gut microbiota and suppressed the copper-induced reduction in the ratio of Firmicutes to Bacteroidota. Serum metabolomics analysis showed that the alleviating effect of B. coagulans XY2 on copper toxicity was mainly related to lipid metabolism. For the first time, we demonstrated mechanisms of copper toxicity mitigation by B. coagulans XY2, which was related to self-adsorption, host copper excretion promotion, and lipid metabolism regulation. Moreover, working model of B. coagulans XY2 on copper homeostasis was predicted by whole-genome analysis. Our study provides a new solution for harmfulness caused by copper both in human health and the environment.

Effects of metabolic energy intervention on lipid content and liver transcriptome in finisher yellow-feathered chickens

High-energy diets improve growth rates and shorten the growth period while resulting in excessive fat deposition in the liver of birds. The effect of different energy diets on lipid content and liver transcriptome in finisher Huxu chickens was examined here. A total of 200 90-d-old Huxu chickens with an average BW of 1.08 kg were randomly divided into two dietary treatments. The birds were fed diets either containing 12.06 MJ ME/kg (low metabolic energy, LME) or 13.31 MJ ME/kg (high metabolic energy, HME) for 45 days. Chickens fed the HME diet had significantly higher total triglyceride and total cholesterol concentrations in both plasma and liver than did those fed the LME diet. Transcriptomic profiling showed 480 known differentially expressed genes (DEG), with 180 down-regulated and 300 up-regulated chickens from the HME diet compared with the LME diet. Notably, these genes were mostly enriched in lipid metabolism including the PPAR signalling pathway, fatty acid elongation, and glycerophospholipid metabolism. The relative mRNA expression level of 14 lipid metabolism-related genes, included 13 up-regulated (MBOAT2, PLA2G2E, AGPAT2, AGPAT3, PCYT2, PEMT, ELOVL2, HADHA, ACOT1L, FABP3, FABP1, PLIN1, RXRG) and one down-regulated (LCAT) gene. In conclusion, the present findings indicate that a high-energy diet likely regulates gene expression of the 14 lipid metabolism-related genes through the PPAR signalling pathway, fatty acid elongation, and glycerophospholipid metabolism resulting in excessive fat accumulation in the liver of Huxu chickens. These results provide a better understanding of the biological mechanisms by which the increased dietary energy induces fat accumulation in the liver. Highlights A high-energy diet without change in protein level induced excessive fat accumulation in the Huxu chickens. Chickens fed the high-energy diet had induced higher total triglyceride and total cholesterol concentrations in both plasma and liver. This study showed a comprehensive profile of hepatic gene expression in chickens with fatty liver induced by high energy.

Selenium-Enriched Cardamine violifolia Increases Selenium and Decreases Cholesterol Concentrations in Liver and Pectoral Muscle of Broilers

BackgroundSupernutrition of selenium (Se) in an effort to produce Se-enriched meat may inadvertently cause lipid accumulation. Se-enriched Cardamine violifolia (SeCv) contains >80% of Se in organic forms. ObjectivesThis study was to determine whether feeding chickens a high dose of SeCv could produce Se-biofortified muscle without altering their lipid metabolism. MethodsDay-old male broilers were allocated to 4 groups (6 cages/group and 6 chicks/cage) and were fed either a corn–soy base diet (BD, 0.13–0.15 mg Se/kg), the BD plus 0.5 mg Se/kg as sodium selenite (SeNa) or as SeCv, or the BD plus a low-Se Cardamine violifolia (Cv, 0.20–0.21mg Se/kg). At week 6, concentrations of Se and lipid and expression of selenoprotein and lipid metabolism–related genes were determined in the pectoral muscle and liver. ResultsThe 4 diets showed no effects on growth performance of broilers. Compared with the other 3 diets, SeCv elevated (P < 0.05) Se concentrations in the pectoral muscle and liver by 14.4–127% and decreased (P < 0.05) total cholesterol concentrations by 12.5–46.7% and/or triglyceride concentrations by 28.8–31.1% in the pectoral muscle and/or liver, respectively. Meanwhile, SeCv enhanced (P < 0.05) muscular α-linolenic acid (80.0%) and hepatic arachidonic acid (58.3%) concentrations compared with SeNa and BD, respectively. SeCv downregulated (P < 0.05) the cholesterol and triglyceride synthesis-related proteins (sterol regulatory element binding transcription factor 2 and diacylglycerol O-acyltransferase 2) and upregulated (P < 0.05) hydrolysis and β-oxidation of fatty acid–related proteins (lipoprotein lipase, fatty acid binding protein 1, and carnitine palmitoyltransferase 1A), as well as selenoprotein P1 and thioredoxin reductase activity in the pectoral muscle and/or liver compared with SeNa. ConclusionsCompared with SeNa, SeCv effectively raised Se and reduced lipids in the liver and muscle of broilers. The effect was mediated through the regulation of the cholesterol and triglyceride biosynthesis and utilization-related genes.

Corilagin prevents non-alcoholic fatty liver disease via improving lipid metabolism and glucose homeostasis in high fat diet-fed mice.

Non-alcoholic fatty liver disease (NAFLD) has been considered to be one of the most common chronic liver diseases. However, no validated pharmacological therapies have been officially proved in clinic due to its complex pathogenesis. The purpose of this study was to examine the protective effects of Corilagin (referred to Cori) against NAFLD in mice under a high fat diet (HFD) condition. Mice were fed either a normal control diet (NCD) or HFD with or without Cori (5 or 10 mg/kg body weight) for 15 weeks. In our results, Cori treatment significantly attenuated HFD-induced hepatic steatosis, high NAFLD activity score (NAD) and liver injury. Consistently, Cori treatment remarkably alleviated HFD-induced hepatic lipid accumulation (e.g., triglycerides (TG) and total cholesterol (TC) contents in liver), and improved plasma lipid concentrations (e.g., plasma TG, TC, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c)). Moreover, Cori treatment ameliorated NAFLD associated metabolic disorders such as glucose intolerance and insulin resistance in HFD-fed mice. Additionally, Cori treatment dramatically changed HFD-induced liver gene expression profiles, and identified overlapped differentially expressed genes (DEGs) between NCD vs. HFD group and HFD vs. HCR (high fat diet plus treatment with Cori) group. With these DEGs, we observed a marked enrichment of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which were closely associated with the metabolic balance in liver. Particularly, we found several potential hub proteins against NAFLD development with analyses of protein-protein interaction (PPI) network and qPCR assays. Collectively, our results revealed the important protective effects of Cori against the progress of NAFLD, which was probably mediated through improving dysregulated lipid metabolism and insulin resistance in HFD-fed mice. Additionally, Cori-dependent overlapped DEGs might serve as a featured NAFLD-associated gene expression signature for the diagnosis, treatment, as well as drug discovery and development of NAFLD in the near future.

Effect of aqueous extract of Colocasia esculenta against high-fat diet-induced non-alcoholic fatty liver disease in rats

Non-alcoholic fatty liver disease (NAFLD) is becoming a major public health problem due to the increasing incidence of obesity and diabetes in India for the last two decades. The present work is aimed to investigate the effect of aqueous extract of Colocasia esculenta against (AECE) high-fat diet-induced non-alcoholic fatty liver disease in Wistar albino rats. Wistar albino rats were assigned in to four groups as follows; Group I: Normal conventional diet, Group II: High fat diet, Group III &amp; Group IV: Combined high fat diet and different doses of Colocasia esculenta (200 and 400 mg/kg, p.o) for 4 weeks.Treatment with aqueous extract of Colocasia esculenta(200mg/kg, 400mg/kg bw) significantly reduced the body weight and weight gain. In addition, it also significantly reduced the serum triglycerides, total cholesterol, LDL cholesterol, VLDL cholesterol and showed a significant increase in HDL cholesterol as well as significant improvement in liver cholesterol and triglyceride content. AECE treated rats exhibited a significant beneficial effects on levels of liver function markers and oxidative stress and also reversed the histopathological changes.The study suggested the therapeutic potential of AECE against NAFLD, acting in part through anti-obesity, antioxidant mechanisms, and liver marker enzymes.

SEASONAL CHANGES OF CHOLESTEROL IN THE TISSUES OF MALE CATFISH MYSTUS CAVASIUS (HAM) IN BHADRA RESERVOIR, KARNATAKA, INDIA

Seasonal variation in cholesterol of the different tissues of the freshwater catfish Mystus cavasius was investigated from Bhadra Reservoir. The amount of cholesterol in liver, muscle and testes was measured. A decline was recorded during the period when the gonads were passing through the peak ripe stage. The highest value of the cholesterol was however attained before this phase of gonad maturation. Concentration pattern of liver cholesterol seemed related to variations in the cholesterol metabolism of the fish, necessitated, besides other factors, by the demand for sex hormones. A possibility of the influence of feeding intensity on liver cholesterol content has also been indicated.

Effects of dietary phosphorus level on growth, body composition, liver histology and lipid metabolism of spotted seabass (Lateolabrax maculatus) reared in freshwater

The present study was conducted to determine the effects of dietary phosphorus (P) levels on growth performance, body composition, liver histology and enzymatic activity, and expression of lipid metabolism-related genes in spotted seabass (Lateolabrax maculatus). Seven diets were prepared to contain available P levels of 0.48% (the control group), 0.69%, 0.89%, 1.10%, 1.28%, 1.51% and 1.77% and feed fish (4.26 ± 0.03 g) to satiety twice daily for 10 weeks. Significantly higher weight gain and specific growth rate were recorded at P levels of 0.69%–1.51% compared to the control group. Feed conversion ratio decreased with increasing P levels up to 0.89% and increased thereafter. The lowest liver lipid content, viscerosomatic index and lipid content of whole-body were obtained in the 0.89%-P group among dietary treatments. P and calcium (Ca) contents in whole body were increased, while liver triglyceride and cholesterol contents were decreased with increasing dietary P levels from 0.48% to 1.77%. The highest activity of hepatic lipase was recorded in the 1.10%-P group among dietary treatments. Compared to the control group, 1.10% P enhanced the proportion of HUFA and reduced the proportion of SFA and MUFA. The histological observations showed that P deficiency (0.48%) led to the vacuolization of hepatocytes and increased number of lipid droplets. Meanwhile, overall liver tissue structure was improved when P level increased to 1.28%. Compared to the control group, expression of lipid metabolism-related genes such as FAS, ACC-2 and SREBP-1 was decreased at 0.89%–1.10% P group while an opposite trend was observed in the expression of PPARa2 and CPT-1 genes. The current study showed that 0.89% dietary P levels could promote growth performance of spotted seabass and reduce lipid accumulation in the liver. A broken-line regression analysis based on weight gain showed that the optimum dietary P level (available P) for juvenile spotted seabass reared in freshwater was 0.72%.

Molecular characterization of farnesoid X receptor alpha in Megalobrama amblycephala and its potential roles in high-carbohydrate diet-induced alterations of bile acid metabolism

Farnesoid X receptorα (FXRα) plays a central role in maintaining the bile acid homeostasis in mammals, while relevant processes are still poorly interpreted in aquatic species. This study was conducted to characterize the fxrα gene in a cyprinidae species: blunt snout bream (Megalobrama amblycephala), and investigate its potential roles in bile acid metabolism. The Fxrα protein contains one DNA binding domain, one ligand binding domain, one His-Try “switch” and two modifies residues. A high degree of conservation (53.18–100.00 %) was observed in the Fxrα protein among most aquatic species and higher vertebrates. The transcription of fxrα was mainly observed in intestine, liver and kidney. Then fish (35.0 ± 0.15 g) were fed two diets containing 33 % and 45 % carbohydrate levels for 12weeks. High-carbohydrate diet significantly elevated the total cholesterol concentrations in plasma, liver and hindgut as well as the triglyceride concentrations in both liver and hindgut, but decreased the total bile acid concentrations in plasma, liver and hindgut. High dietary carbohydrate levels also significantly enhanced hepatic transcriptions of 3-hydroxy-3-methylglutaryl-CoA reductase (the rate-limiting enzyme in cholesterol synthesis), and those of fxrα (a bile acid receptor) and multidrug resistance associated protein 2 (a bile acid transporter) in hindgut. Furthermore, high dietary carbohydrate levels significantly decreased the transcriptions of cholesterol 7α-hydroxylase (the rate-limiting enzyme in bile acid synthesis) and organic anion-transporting polypeptides (a bile acid transporter) in liver as well as that of takeda G-protein-coupled bile acid receptor in hindgut. The results demonstrated that the fxrα gene of blunt snout bream is highly conserved compared with other vertebrates. Besides, high dietary carbohydrate levels increased total cholesterol concentrations, and up-regulated the transcription of fxrα, thus decreasing the biosynthesis and reabsorption of bile acids by mediating various target genes.

Expressing the Human Cholesteryl Ester Transfer Protein Minigene Improves Diet-Induced Fatty Liver and Insulin Resistance in Female Mice.

Mounting evidence has shown that CETP has important physiological roles in adapting to chronic nutrient excess, specifically, to protect against diet-induced insulin resistance. However, the underlying mechanisms for the protective roles of CETP in metabolism are not yet clear. Mice naturally lack CETP expression. We used transgenic mice with a human CETP minigene (huCETP) controlled by its natural flanking region to further understand CETP-related physiology in response to obesity. Female huCETP mice and their wild-type littermates were fed a high-fat diet for 6 months. Blood lipid profile and liver lipid metabolism were studied. Insulin sensitivity was analyzed with euglycemic-hyperinsulinemic clamp studies combined with 3H-glucose tracer techniques. While high-fat diet feeding induced obesity for huCETP mice and their wild-type littermates lacking CETP expression, insulin sensitivity was higher for female huCETP mice than for their wild-type littermates. There was no difference in insulin sensitivity for male huCETP mice vs. littermates. The increased insulin sensitivity in females was largely caused by the better insulin-mediated suppression of hepatic glucose production. In huCETP females, CETP in the circulation decreased HDL-cholesterol content and increased liver cholesterol uptake and liver cholesterol and oxysterol contents, which was associated with the upregulation of LXR target genes in long-chain polyunsaturated fatty acid biosynthesis and PPARα target genes in fatty acid β-oxidation in the liver. The upregulated fatty acid β-oxidation may account for the improved fatty liver and liver insulin action in female huCETP mice. This study provides further evidence that CETP has beneficial physiological roles in the metabolic adaptation to nutrient excess by promoting liver fatty acid oxidation and hepatic insulin sensitivity, particularly for females.

Dietary Phospholipids Prepared From Scallop Internal Organs Attenuate the Serum and Liver Cholesterol Contents by Enhancing the Expression of Cholesterol Hydroxylase in the Liver of Mice.

In this study, we successfully prepared scallop oil (SCO), which contains high levels of phospholipids (PL) and eicosapentaenoic acid (EPA), from the internal organs of the Japanese giant scallop (Patinopecten yessoensis), one of the most important underutilized fishery resources in Japan. The intake of SCO lowers the serum and liver cholesterol contents in mice; however, whether the fatty acids (FA) composition or PL of SCO exhibits any cholesterol-lowering effect remains unknown. To elucidate whether the cholesterol-lowering function is due to FA composition or PL of SCO, and investigate the cholesterol-lowering mechanism by SCO, in the present study, mice were fed SCO's PL fraction (SCO-PL), triglyceride (TG)-type oil with almost the same FA composition as SCO-PL, called SCO's TG fraction (SCO-TG), soybean oil (SOY-TG), and soybean's PL fraction (SOY-PL). Male C57BL/6J mice (5-week-old) were fed high-fat and cholesterol diets containing 3% (w/w) experimental oils (SOY-TG, SOY-PL, SCO-TG, and SCO-PL) for 28 days. The SCO-PL diet significantly decreased the serum and liver cholesterol contents compared with the SOY-TG diet, but the intake of SOY-PL and SCO-TG did not show this effect. This result indicated that the serum and liver cholesterol-lowering effect observed in the SCO intake group was due to the effect of SCO-PL. The cholesterol-lowering effect of SCO-PL was in part related to the promotion of liver cholesterol 7α-hydroxylase (CYP7A1) expression, which is the rate-limiting enzyme for bile acid synthesis. In contrast, the expression levels of the ileum farnesoid X receptor (Fxr) and fibroblast growth factor 15 (Fgf15), which inhibit the expression of liver CYP7A1, were significantly reduced in the SCO-PL group than the SOY-TG group. From these results, the increase in the liver CYP7A1 expression by dietary SCO-PL was in part through the reduction of the ileum Fxr/Fgf15 regulatory pathway. Therefore, this study showed that SCO-PL may be a health-promoting component as it lowers the serum and liver cholesterol contents by increasing the liver CYP7A1 expression, which is not seen in SOY-PL and SCO-TG.