Hepatic Lipid Metabolism-related Gene Research Articles

Fumigaclavine C ameliorates liver steatosis by attenuating hepatic de novo lipogenesis via modulation of the RhoA/ROCK signaling pathway

BackgroundNon-alcoholic fatty liver disease (NAFLD) has been well defined as a common chronic liver metabolism disorder. Statins as a first-line therapeutic treatment had some side effects. Here, we found that Fumigaclavine C (FC) was collected from endophytic Aspergillus terreus via the root of Rhizophora stylosa (Rhizophoraceae), had potential anti-adipogenic and hepatoprotective effects both in vitro and in vivo without obvious adverse side effects. However, the mechanisms of the prevention and management of FC for hepatic steatosis are incompletely delineated.MethodsThe pharmacodynamic effects of FC were measured in high-fat diet (HFD)-induced obese mice. Liver index and blood biochemical were examined. Histopathological examination in the liver was performed by hematoxylin & eosin or oil red O. The levels of serum TG, TC, LDL-c, HDL-c, FFA, T-bili, ALT, AST, creatinine, and creatine kinase were estimated via diagnostic assay kits. The levels of hepatic lipid metabolism-related genes were detected via qRT-PCR. The expression levels of hepatic de novo lipogenesis were quantitated with Western blot analysis. ResultsFC-treatment markedly reduced hepatic lipid accumulation in HFD-induced obese mice. FC significantly attenuated the hepatic lipid metabolism and ameliorated liver injury without obvious adverse side effects. Moreover, FC also could dose-dependently modulate the expressions of lipid metabolism-related transcription genes. Mechanically, FC notably suppressed sterol response element binding protein-1c mediated de novo lipogenesis via interfering with the RhoA/ROCK signaling pathway by decreasing the levels of geranylgeranyl diphosphate and farnesyl diphosphate.ConclusionsThese findings suggested that FC could improve hepatic steatosis through inhibiting de novo lipogenesis via modulating the RhoA/ROCK signaling pathway.

Increased Hepatic ATG7 mRNA and ATG7 Protein Expression in Nonalcoholic Steatohepatitis Associated with Obesity.

The autophagy gene ATG7 has been shown to be essential for the induction of autophagy, a process that used to be suppressed in nonalcoholic fatty liver disease (NAFLD). However, the specific role of ATG7 in NAFLD remains unclear. The aim of this study was to analyze hepatic ATG7 mRNA and ATG7 protein expression regarding obesity-associated NAFLD. Patients included women classified into normal weight (NW, n = 6) and morbid obesity (MO, n = 72). The second group was subclassified into normal liver (NL, n = 11), simple steatosis (SS, n= 29), and nonalcoholic steatohepatitis (NASH, n = 32). mRNA expression was analyzed by RT-qPCR and protein expression was evaluated by Western blotting. Our results showed that NASH patients presented higher ATG7 mRNA and ATG7 protein levels. ATG7 mRNA expression was increased in NASH compared with SS, while ATG7 protein abundance was enhanced in NASH compared with NL. ATG7 mRNA correlated negatively with the expression of some hepatic lipid metabolism-related genes and positively with endocannabinoid receptors, adiponectin hepatic expression, and omentin levels. These results suggest that ATG7-mediated autophagy may play an important role in the pathogenesis of NAFLD, especially in NASH, perhaps playing a possible protective role. However, this is a preliminary study that needs to be further studied.

Microbiota derived butyrate affected the muscle texture of Nile tilapia (Oreochromis niloticus) fed with different protein sources

Flesh quality is influenced by diet components, but the underlying mechanism remains unclear. This study aimed to investigate the effect of replacing soybean meal (SBM) protein with cottonseed protein concentrate (CPC) at different levels (0%, CK; 15%, CPC15; 30%, CPC30 and 45%, CPC45) on the flesh quality of Nile tilapia. The results indicated that different protein sources influenced muscle amino acid composition instead of fatty acid composition. Lower muscle lipid content was found in CPC45, which in turn significantly altered the muscle texture. The hepatic lipid metabolism-related genes were detected and we found that CPC45 significantly suppressed the lipogenesis and promoted lipolysis. Higher content of microbiota-derived butyrate was found in the intestinal content of CPC45 and butyrate could decrease the lipid accumulation in vitro. Replacing SBM with CPC increased the intestinal butyrate to suppress the lipogenesis in the liver which may account for the increased muscle hardness.

High-fructose corn syrup intake has stronger effects on the transcription level of hepatic lipid metabolism-related genes, via DNA methylation modification, in childhood and adolescence than in other generations

AimsThis study aimed to analyze differences in sensitivity to hepatic lipid metabolism at different ages, through DNA methylation, using an experimental rat model of high-fructose corn syrup (HFCS) intake. Main methodsThe experimental was divided into three periods: childhood and adolescence (postnatal day (PD) 21–60), young adulthood (PD61–100), and adulthood (PD101–140). Rats in the different age groups were assigned to receive either water (C: control group) or 20% HFCS solution (H: HFCS-fed group). We measured hepatic mRNA levels of peroxisome proliferator-activated receptor alpha (Ppara), carnitine palmitoyltransferase 1A (Cpt1a), fatty acid synthase (Fasn), and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (Pgc1a) using real-time PCR. Additionally, we examined the DNA methylation levels of Ppara, Cpt1a, Fasn, and Pgc1a using pyrosequencing. Key findingsGene expressions of Cpt1a and Ppara in childhood and adolescence were significantly lower in the H group than in the C group. Conversely, Fasn and Pgc1a expressions were significantly higher in the H group than in the C group. Additionally, there was hypermethylation of Cpt1a and Ppara and hypomethylation of Fasn and Pgc1a in the H groups of childhood and adolescence. However, only one gene expression and methylation change was observed in young adulthood and adulthood groups. We found that HFCS intake in rats had stronger lipid metabolic effects in childhood and adolescence than in other generations, and that its mechanism involved epigenetic regulation. SignificanceWe anticipate that these research findings will be a breakthrough for elucidating the varying effects of growth stage in the future.

ω3PUFAs improve hepatic steatosis in postnatal overfed rats and HepG2 cells by inhibiting acetyl-CoA carboxylase.

Postnatal overfeeding can lead to persistent increases in hepatic lipid synthesis and the risk of nonalcoholic fatty liver disease (NAFLD) in adulthood. The ω3 polyunsaturated fatty acids (ω3PUFAs) exhibit beneficial effects on NAFLD. Here, we employed a rat model and an in vitro HepG2 cell model to investigate whether fish oil (FO) affects hepatic lipid synthesis due to postnatal overfeeding. Male Sprague‐Dawley were divided into litter sizes of three (small litters, SLs) or 10 (normal litters, NLs) on postnatal day 3 and were fed standard chow or FO diet beginning on postnatal week 3 to generate NL, SL, NL‐FO, and SL‐FO groups. The results indicated that the FO diet reduced the postnatal overfeeding‐induced body weight gain and NAFLD characteristics (such as serum and liver triglyceride (TG) and hepatic steatosis). In addition, FO restored the expression of hepatic lipid metabolism‐related genes (including SCD1, FASN, CPT1, LPL, ACC, and SREBP‐1c) in SL‐FO rats. Specifically, the activity and expression pattern of ACC were consistent with SREBP‐1c. Furthermore, HepG2 cells were treated with oleic acid (OA), followed by eicosapentenoic acid (EPA), with or without SREBP‐1c siRNA. The cellular lipid droplets, TG content, and the expression of ACC (by 75%) and SREBP‐1c (by 45%) were increased by OA stimulation (p < .05), which was inhibited by EPA treatment. However, the effect of EPA treatment was abolished when SREBP‐1c was silenced. In conclusion, ω3PUFAs‐rich diet may be an effective way to reverse the developmental programming of hepatic lipid synthesis, at least partially, by inhibiting ACC through modulating SREBP‐1c.

α-Lipoic Acid Alleviates Hepatic Lipid Deposition by Inhibiting FASN Expression via miR-3548 in Rats.

Excessive liver lipid deposition is a vital risk factor for the development of many diseases. Here, we fed Sprague-Dawley rats with a control or α-lipoic acid-supplemented diet (0.2%) for 5 weeks to elucidate the effects of α-lipoic acid on preventive ability, hepatic lipid metabolism-related gene expression, and the involved regulatory mechanisms. In the current study, α-lipoic acid supplementation lowered plasma triglyceride level and hepatic triglyceride content. Reduced hepatic lipid deposition was closely associated with inhibiting fatty acid-binding protein 1 and fatty acid synthase expression, as well as increasing phosphorylated hormone-sensitive lipase expression at the protein level in α-lipoic acid-exposed rats. Hepatic miRNA sequencing revealed increased expression of miR-3548 targeting the 3′untranslated region of Fasn mRNA, and the direct regulatory link between miRNA-3548 and FASN was verified by dual-luciferase reporter assay. Taken together, α-lipoic acid lowered hepatic lipid accumulation, which involved changes in miRNA-mediated lipogenic genes.

Replacing fishmeal with cottonseed protein concentrate in feed for pearl gentian groupers (Epinephelus fuscoguttatus♀ × E. lanceolatus♂): Effects on growth and expressions of key genes involved in appetite and hepatic glucose and lipid metabolism

This study investigated the effects of replacing the fish meal (FM) in a 55 % FM fish feed with cottonseed protein concentrate (CPC) in pearl gentian groupers (Epinephelus fuscoguttatus♀ × E. lanceolatus♂). Effects on growth and the expression of key genes involved in appetite and hepatic glucose and lipid metabolism Four isoproteic and isolipidic diets were formulated containing 0 %, 6.06 %, 18.18 %, or 30.30 % CPC by replacing 0 % (FM, control), 10 % (CPC10), 30 % (CPC30), and 50 % (CPC50) of the FM in the feed, respectively. Each diet was fed to fish raised in triplicate groups for 56 days. No significant differences in specific growth rate, feed conversion ratio, or survival rate were found among dietary treatments. The weight gain in CPC groups was no different than in controls (P < 0.05). Fish fed the CPC50 diet had higher body lipid contents than others (P < 0.05) and the highest activity of hepatic fatty acid synthase, which was significantly higher than in group CPC10 (P < 0.05). The livers of CPC50 fish had significantly higher mRNA expression levels of apolipoprotein B-100, carnitine palmitoyltransferase 1, peroxisome proliferator-activated receptor α (PPARα), and PPARγ genes compared to other groups except CPC30 (P < 0.05). In conclusion, up to 50 % of the FM in fish feed can be replaced with CPC without adversely affecting the growth and feed utilization of pearl gentian groupers. However, 50 % replacement increased body lipid contents via modulation of hepatic lipid metabolism-related genes and enzyme activity.

Effects of dietary highly unsaturated fatty acid levels on growth, fatty acid profiles, antioxidant activities, mucus immune responses and hepatic lipid metabolism related gene expressions in loach ( Misgurnus anguillicaudatus ) juveniles

A 9-week rearing trail was conducted to examine the effects of different dietary highly unsaturated fatty acid (HUFA) levels on the growth performance, fatty acid profiles, antioxidant activities, mucus immune responses and lipid metabolism-related gene expressions of loach (Misgurnus anguillicaudatus) juveniles. Five test diets supplemented with 0%, 0.32%, 0.64%, 0.96% and 1.28% HUFA were used here. The loaches fed no HUFA diets had the lowest specific growth rate and survival rate. The loaches fed 0.32% HUFA diets had the lowest feed conversion rate and while no significant differences were found among the other four diet groups. Contents of hepatic eicosapentaenoic acid, docosahexaenoic acid and total polyunsaturated fatty acids were significantly increased with incremental dietary HUFA levels. Activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in 0% HUFA group were lowest, while malondialdehyde was just the opposite. The lysozyme activity was significantly increased with incremental dietary HUFA levels. However, the activities of alkaline phosphatase and acid phosphatase reached a peak in 0.32% HUFA group. Loaches fed diets with HUFA significantly up-regulated expressions of SOD, GPx, CAT and two lipid metabolism related genes. In conclusion, the optimal dietary HUFA level for loach juveniles was 0.64%–0.96%.

Dietary DHA/EPA Ratio Changes Fatty Acid Composition and Attenuates Diet-Induced Accumulation of Lipid in the Liver of ApoE-/- Mice.

Diets containing various docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) ratios protect against liver damage in mice fed with a high-fat diet (HFD). However, it is unclear whether these beneficial roles of DHA and EPA are associated with alterations of fatty acid (FA) composition in the liver. This study evaluated the positive impacts of n-6/n-3 polyunsaturated fatty acids (PUFAs) containing different DHA/EPA ratios on HFD-induced liver disease and alterations of the hepatic FA composition. ApoE−/− mice were fed with HFDs with various ratios of DHA/EPA (2 : 1, 1 : 1, and 1 : 2) and an n-6/n-3 ratio of 4 : 1 for 12 weeks. After treatment, the serum and hepatic FA compositions, serum biochemical parameters, liver injury, and hepatic lipid metabolism-related gene expression were determined. Our results demonstrated that dietary DHA/EPA changed serum and hepatic FA composition by increasing contents of n-6 and n-3 PUFAs and decreasing amounts of monounsaturated fatty acids (MUFAs) and the n-6/n-3 ratio. Among the three DHA/EPA groups, the DHA/EPA 2 : 1 group tended to raise n-3 PUFAs concentration and lower the n-6/n-3 ratio in the liver, whereas DHA/EPA 1 : 2 tended to raise n-6 PUFAs concentration and improve the n-6/n-3 ratio. DHA/EPA supplementation reduced the hepatic impairment of lipid homeostasis, oxidative stress, and the inflammatory responses in HFD-fed mice. The DHA/EPA 2 : 1 group had lower serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol and higher levels of adiponectin than HFD group. The DHA/EPA 1 : 2 group had elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, without significant change the expression of genes for inflammation or hepatic lipid metabolism among the three DHA/EPA groups. The results suggest that DHA/EPA-enriched diet with an n-6/n-3 ratio of 4 : 1 may reverse HFD-induced nonalcoholic fatty liver disease to some extent by increasing n-6 and n-3 PUFAs and decreasing the amount of MUFAs and the n-6/n-3 ratio.

Isoflavone Aglycones and Oligopeptides in Lactic Acid-Fermented Soy Milk Differentially Regulate Lipid Metabolism-Related Gene Expression

We previously investigated the physiological effect of an ethanol extract of fermented soymilk on rats and clarified that this extract modulated their hepatic lipid metabolism. Although the soy isoflavones and oligopeptides are representative functional components of the ethanol extract, it remained unclear whether these substances share a role in lipid metabolism modulation. Therefore, we attempted to clarify the effects of isoflavones and oligopeptides in lactic acid-fermented soymilk on lipid metabolism-related gene expression in rats and HepG2 cells. The fermented soymilk extract had a higher isoflavone aglycone content than the soymilk extract. Sevenweek-old male Sprague-Dawley rats were fed an AIN-93G diet, a diet plus 70% soymilk ethanol extract, or a diet plus 70% fermented soymilk ethanol extract for 5 weeks. Although both the soymilk and fermented soymilk ethanol extracts did not significantly affect plasma and hepatic lipid profiles, the expression levels of the genes encoding CYP7a1 and SREBP-2 were significantly upregulated in the livers of rats fed with the fermented soymilk extract. Whereas isoflavone aglycones upregulated CYP7a1-encoding gene expression in HepG2, oligopeptides in soymilk and fermented soymilk downregulated this expression. Oligopeptides in fermented soymilk downregulated the expression stronger than that observed with soymilk. On the other hand, no significant change in FAS expression was observed in the livers of rats fed the fermented soymilk extract. Although isoflavone aglycones did not affect FAS expression in HepG2 cells, oligopeptides in fermented soymilk downregulated FAS expression. The downregulation of FAS with oligopeptides from fermented soymilk was stronger than that from soymilk. In the present animal experiment, the effect on reduction of fat synthesis was not found because of insufficient amount of peptides derived from digestion of soy protein. These results suggest that isoflavone aglycones increase CYP7a1 gene expression, whereas oligopeptides decrease FAS expression. Isoflavone glycosides and proteins in soymilk were converted to isoflavone aglycones and oligopeptides by lactic acid fermentation, respectively, and these functional components independently improved the lipid metabolism. In the present study, it was found that isoflavone aglycones and oligopeptides in fermented soymilk differentially regulate hepatic lipid metabolism-related gene expression. Therefore, the consumption of fermented soymilk containing isoflavone aglycones and soy oligopeptides might prevent dyslipidemia more effectively than that of any other soy food. Fermented soymilk is a superior functional food modulating lipid metabolism.

Transcriptome profile of liver at different physiological stages reveals potential mode for lipid metabolism in laying hens

BackgroundLiver is an important metabolic organ that plays a critical role in lipid synthesis, degradation, and transport; however, the molecular regulatory mechanisms of lipid metabolism remain unclear in chicken. In this study, RNA-Seq technology was used to investigate differences in expression profiles of hepatic lipid metabolism-related genes and associated pathways between juvenile and laying hens. The study aimed to broaden the understanding of liver lipid metabolism in chicken, and thereby to help improve laying performance in the poultry industry.ResultsRNA-Seq analysis was carried out on total RNA harvested from the liver of juvenile (n = 3) and laying (n = 3) hens. Compared with juvenile hens, 2567 differentially expressed genes (1082 up-regulated and 1485 down-regulated) with P ≤ 0.05 were obtained in laying hens, and 960 of these genes were significantly differentially expressed (SDE) at a false discovery rate (FDR) of ≤0.05 and fold-change ≥2 or ≤0.5. In addition, most of the 198 SDE novel genes (91 up-regulated and 107 down-regulated) were discovered highly expressed, and 332 SDE isoforms were identified. Gene ontology (GO) enrichment and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the SDE genes were most enrichment in steroid biosynthesis, PPAR signaling pathway, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, three amino acid pathways, and pyruvate metabolism (P ≤ 0.05). The top significantly enriched GO terms among the SDE genes included lipid biosynthesis, cholesterol and sterol metabolic, and oxidation reduction, indicating that principal lipogenesis occurred in the liver of laying hens.ConclusionsThis study suggests that the majority of changes at the transcriptome level in laying hen liver were closely related to fat metabolism. Some of the SDE uncharacterized novel genes and alternative splicing isoforms that were detected might also take part in lipid metabolism, although this needs further investigation. This study provides valuable information about the expression profiles of mRNAs from chicken liver, and in-depth functional investigations of these mRNAs could provide new insights into the molecular networks of lipid metabolism in chicken liver.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1943-0) contains supplementary material, which is available to authorized users.

Effects of different dietary soybean oil levels on growth, lipid deposition, tissues fatty acid composition and hepatic lipid metabolism related gene expressions in blunt snout bream (Megalobrama amblycephala) juvenile

Soybean oil (SO) is widely used in freshwater aqua-feeds in China. However, little information is available about the effects of dietary SO levels on lipid deposition and hepatic lipid metabolism in fish. This study evaluated effects of different dietary soybean oil (SO) levels on growth performance, lipid deposition, tissues fatty acid compositions and hepatic lipid metabolism related gene expressions in blunt snout bream (Megalobrama amblycephala). Fish (average weight 0.34±0.01g) were fed five experimental diets containing 0% (0%SO), 20% (20%SO), 32% (32%SO), 56% (56%SO) and 100% (100%SO) SO in dietary lipid, and a diet containing 100% fish oil (100%FO). The body weight gain of fish fed 20%SO and 100%FO diets were significantly higher than in the other groups. Hepatic lipid content increased with incremental dietary SO level. The percentages of 18:2n−6 in the liver and muscle significantly increased with increasing dietary SO level. In the fish fed 56%SO and 100%SO diets 20:4n−6 content significantly increased in the liver and muscle suggesting the capacity of blunt snout bream to convert C18 fatty acids (PUFAs) to C20/22 fatty acids. However, increasing dietary SO level up-regulated acyl-CoA delta-9 desaturase and down-regulated peroxisome proliferator-activated receptors-α and -β, which might be responsible for the high 18:2n−6 content. It is suggested that supplementation of 20% soybean oil (8% lipid in diet) could improve blunt snout bream juvenile growth. However, an excess of 18:2n−6 in SO supplemented diets modified the expressions of lipid metabolism-related genes which induced lipid deposition. Statement of relevanceThe present study was conducted to evaluated the effects of different dietary soybean oil (SO) levels on growth performance, lipid deposition, tissues fatty acid compositions and hepatic lipid metabolism related gene expressions in blunt snout bream (M. amblycephala). Fish (average weight 0.34±0.01g) were fed five experimental diets containing the following inclusion levels of SO: 0% (0%SO), 20% (20%SO), 32% (32%SO), 56% (56%SO) and 100% (100%SO) in dietary lipid, and a diet contained 100% fish oil (100%FO) was also used here. The percentages of 18:2n−6 in the liver and muscle significantly increased with increasing dietary SO level, and the fish fed 56%SO and 100%SO diets significantly increased 20:4n−6 contents in the liver and muscle, suggesting blunt snout bream has the capacity to convert C18 fatty acids (PUFAs) to C20/22 fatty acids. However, increasing dietary SO level up-regulated acyl-CoA delta-9 desaturase and down-regulated peroxisome proliferator-activated receptors-α and -β, which might be related associated with high level of 18:2n−6 in SO. It suggested that supplementation of 20% soybean oil (8% lipid in diet) could improve growth of blunt snout bream juvenile. However, an excess of 18:2n−6 in SO would modify the expressions of lipid metabolism-related genes, which induced lipid deposition in fish.

Effects of Watermelon Powder on Lipid Metabolism through Regulation of Gene Expression in Atherogenic Diet‐Fed Rats

Cardiovascular disease (CVD) is the leading cause of death in the United States, which has led to an increasing need for cost effective non‐pharmacological treatment alternatives. Studies have shown that watermelon plays a role in vascular function by causing vasodilation, which lowers blood pressure and arterial stiffness. We want to examine if watermelon powder supplementation has therapeutic effects on lipid metabolism through regulation of hepatic gene expression. The genes of interest included fatty acid synthase (FAS), HMG‐CoA reductase (HMGCR), sterol regulatory element binding protein ‐1 and 2 (SREBP‐1, SREBP‐2). Forty male‐weanling (21 days old) Sprague‐Dawley rats were divided into four groups (10/group, total N=40) in a 2 (diets) x 2 (treatment) factorial design using an atherogenic diet with or without Dextran Sodium Sulfate (DSS) as an inflammatory agent for 48 hours. Watermelon powder groups exhibited significantly lower total cholesterol levels, LDL‐cholesterol, and serum triglycerides (P&lt;.05). FAS, HMGCR, SREBP‐1, and SREBP‐2 were significantly down regulated in watermelon diet groups (P&lt;.05). These findings support the use of watermelon powder as an alternative treatment for improving risk factors associated with CVD by altering hepatic lipid metabolism related gene expression and thus improving lipid profiles. Supported by NUTR 302L class and SDSU UGP.

Growth performance, lipid deposition and hepatic lipid metabolism related gene expression in juvenile turbot (Scophthalmus maximus L.) fed diets with various fish oil substitution levels by soybean oil

A 92-day feeding experiment was conducted to investigate the effects of dietary soybean oil (SO) on growth performance, fatty acid composition, lipid deposition and hepatic lipid metabolism related gene expression in juvenile turbot ( Scophthalmus maximus L.) (mean initial body weight, 5.88 ± 0.02 g). Three experimental diets were formulated with substitution of 33.3%, 66.7% and 100% fish oil (FO) by SO. Each diet was randomly fed to triplicate tanks, and each tank was stocked with 35 fish. The results showed that specific growth rate of turbot fed diets with 100% SO was significantly lower than that in the 33.3% and 66.7% SO groups. Fatty acid (FA) composition of total lipid in the liver and muscle was closely correlated with those in diets. The lipid content in the liver and muscle significantly increased with increasing dietary SO level. The activity of LPL in the liver of turbot was not significantly affected by dietary SO level. Relative gene expression of LPL, PPARα, FAS and MTP significantly increased, while relative expression of LXR and CPT I significantly decreased with increasing dietary SO level. There was no significant difference in the expression of SREBP-1 among dietary treatments. These results suggested that the growth of turbot fed diets with 100% SO was significantly lower than the low SO group. The increase of lipid deposition in the liver of turbot fed diets with higher dietary SO level would be related to the up-regulation of fatty acid synthesis-related gene (FAS) and the down-regulation of fatty acids oxidation gene (CPT I) expression. • Higher dietary SO level (> 66.7%) reduces growth and muscle quality of turbot. • Increasing hepatic lipid deposition of turbot fed with high SO relates to FAS. • Increasing hepatic lipid deposition of turbot fed with high SO relates to CPT I.

Consumption of Chinese Tea-Flavor Liquor Improves Circulating Insulin Levels without Affecting Hepatic Lipid Metabolism-Related Gene Expression in Sprague-Dawley Rats

Objective. To examine the effect of two Chinese liquors with quite different nonalcoholic components on insulin sensitivity, tissue polyunsaturated fatty acids (PUFA), and hepatic lipid metabolism in SD rats. Methods. Thirty-three SD rats were randomized into four groups and maintained in each treatment for 10 weeks: Chinese tea-flavor liquor (TFL, n = 9), traditional Chinese liquor (TCL, n = 8), ethanol control (EC, n = 8), and water control (WC, n = 8). Results. TFL significantly decreased plasma insulin (P = 0.009) and marginally decreased Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) (P = 0.05), compared with WC. Hepatic total and n-6 PUFA compositions were significantly decreased in TFL, TCL, and EC groups compared with WC group (P < 0.05). TFL significantly increased kidney n-6 PUFA (P = 0.05) and total PUFA (P = 0.039), compared with EC group. EC group showed significant higher gene expressions of acetyl-CoA carboxylase and steroid response element-binding protein (1c and 2), while there were no significant differences of these gene expressions in TFL or TCL group compared with WC. Conclusions. TFL has a beneficial effect on metabolic disorder in relation to improved circulating insulin levels without affecting hepatic lipid metabolism-related gene expressions in rats.

Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice

Excessive trans-fatty acids (TFA) consumption has been thought to be a risk factor mainly for coronary artery diseases while less attention has been paid to liver disease. We aimed to clarify the impact of TFA-rich oil consumption on the hepatic pathophysiology compared to natural oil. Mice were fed either a low-fat (LF) or high-fat (HF) diet made of either natural oil as control (LF-C or HF-C) or partially hydrogenated oil, TFA-rich oil (LF-T or HF-T) for 24 weeks. We evaluated the liver and body weight, serological features, liver lipid content and composition, liver histology and hepatic lipid metabolism-related gene expression profile. In addition, primary cultures of mice Kupffer cells (KCs) were evaluated for cytokine secretion and phagocytotic ability after incubation in cis- or trans-fatty acid-containing medium. The HF-T-fed mice showed significant increases of the liver and body weights, plasma alanine-aminotransferase, free fatty acid and hepatic triglyceride content compared to the HF-C group, whereas the LF-T group did not differ from the LF-C group. HF-T-fed mice developed severe steatosis, along with increased lipogenic gene expression and hepatic TFA accumulation. KCs showed increased tumor necrosis factor secretion and attenuated phagocytotic ability in the TFA-containing medium compared to its cis-isomer. Excessive consumption of the TFA-rich oil up-regulated the lipogenic gene expression along with marked hepatic lipid accumulation. TFA might be pathogenic through causing severe steatosis and modulating the function of KCs. The quantity and composition of dietary lipids could be responsible for the pathogenesis of non-alcoholic steatohepatitis.

Effects of maternal treatment of dehydroepiandrosterone (DHEA) on serum lipid profile and hepatic lipid metabolism-related gene expression in embryonic chickens

Over the last decade, much evidence emerged to suggest that alterations in maternal diets during pregnancy may irreversibly affect aspects of physiological and biochemical functions in the fetus. To explore the effects of maternal dietary treatments with dehydroepiandrosterone (DHEA) on lipid metabolism in the embryo, we investigated serum lipid profile and hepatic lipid metabolism-related gene expression in the maternal and embryonic chicken. Sixteen-week-old pullets were allocated into 3 groups (n=30), and after laying, they were provided with a commercial diet supplemented with DHEA at 0, 20 or 100mg/kg diet. Eggs were collected after DHEA treatment and incubated at 37.5 degrees C and a relative humidity of 60%. Blood and liver samples were collected from hens and embryonic chickens. DHEA treatment resulted in decreased body weight and increased relative liver weight in both maternal and embryonic chickens, while the concentrations of blood triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and non-esterified fatty acid (NEFA) were significantly lower in the 20mg DHEA/kg group as compared to the control group during embryonic development. The expression of acetyl CoA carboxylase (ACC) and carnitine palmitoyl transferase I (CPTI) gene was also reduced following treatment with 20mg DHEA/kg at hatching. However, blood TC, and hepatic fatty acid synthase (FAS) and hydroxy methylglutaryl-CoA reductase (HMGR) gene expression were significantly up-regulated in the 100mg DHEA/kg group during embryonic development and hatching. Overall, the results of this study indicate that maternal dietary treatment with DHEA regulates serum lipid metabolism and hepatic gene expression.