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The aim of the present study was to identify the effects of dehydroepiandrosterone (DHEA) on hepatic lipid metabolism parameters and lipogenic gene mRNA expression in broiler chickens. A total of 72 1-day-old broiler chicks received a common basal diet with DHEA added at either 0 (control), 5 or 20 mg/kg feed. In the present study, the hepatic triglyceride (TG) concentration was significantly lower in male and female broilers that had bed administered DHEA than in control birds. In contrast, DHEA administration caused a marked rise in the hepatic non-esterified fatty acid (NEFA) concentration in both male and female broilers and also increased lipase (HL) activity in male broilers, while in female birds, no significant differences were observed in HL activity. The expression of peroxisome proliferators-activated receptor α (PPARα) and carnitine palmitoyl transferase I (CPTI) mRNA was decidedly enhanced following treatment with DHEA, and a similar tendency was also observed in the expression of acyl-Coenzyme A oxidase 1 (ACOX1). However, no significant differences were observed in the expression of either sterol regulatory element binding protein-1c (SREBP-1c) or acetyl CoA carboxylase (ACC) mRNA, except for a decline in the expression of ACC in females treated with 5 mg DHEA/kg. Numerous peroxisomes without a core and an increased number of peroxisomes were evident during morphological observations of broiler livers, in animals that had been treated with DHEA. Overall, the results of the present study indicated that DHEA accelerated lipid catabolism by direct regulation of hepatic lipid metabolism and by induction of relevant gene expression. [ABSTRACT FROM AUTHOR]

Our group (Magkos F, Wright DC, Patterson BW, Mohammed BS, Mittendorfer B, Am J Physiol Endocrinol Merab 290: E355-E362, 2006) has recently demonstrated that a single, prolonged bout of moderate-intensity cycling (2 h at 60% of peak oxygen consumption) in the evening increases basal whole-body free fatty acid (FFA) flux and fat oxidation, decreases hepatic VLDL-apolipoprotein B-100 (apoB-100) secretion, and enhances removal efficiency of VLDL-triglyceride (TG) from the circulation the following day in untrained, healthy, lean men. In the present study, we investigated the effect of a single, shorter-duration bout of the same exercise (1 h cycling at 60% of peak oxygen consumption) on basal FFA, VLDL-TG, and VLDL-apoB-100 kinetics in seven untrained, healthy, lean men by using stable isotope-labeled tracer techniques. Basal FFA rate of appearance in plasma and plasma FFA concentration were ~55% greater (P < 0.05) the morning after exercise than rest, whereas resting metabolic rate and whole-body substrate oxidation rates were not different after rest and exercise. Exercise had no effect on plasma VLDL-TG and VLDL-apoB-100 concentrations, hepatic VLDL-TG and VLDL-apoB-100 secretion rates, and VLDL-TG and VLDL-apoB-100 plasma clearance rates (all P > 0.05). We conclude that in untrained, healthy, lean men 1) the exercise-induced changes in basal whole-body fat oxidation, VLDL-TG, and VLDL-apoB-100 metabolism during the late phase of recovery from exercise are related to the duration of the exercise bout; 2) single sessions of typical recreational activities appear to have little effect on basal, fasting plasma TG homeostasis; and 3) there is a dissociation between systemic FFA availability and VLDL-TG and VLDL-apoB-100 secretion by the liver. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of the study was to investigate the effect of flaxseed oil (FO), rich in alpha-linolenic acid (ALA) (18:3 n-3) on growth parameters and lipid metabolism of rats fed with high fat diet. High fat diet (HFD) resulted in significant alterations in hepatic lipids, increase in body weight gain and negative effect on lipoprotein metabolism. FO supplementation significantly lowered the increase in body weight gain, liver weight, plasma cholesterol, triglycerides, phospholipids, free fatty acids, high-density lipoprotein (HDL), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein (VLDL), LDL/HDL and TC/HDL ratio in HFD fed rats. FO significantly reduced the hepatic and plasma lipid levels indicating its hypolipidemic activity. On the other hand, oral administration of FO exhibited lower plasma lipoprotein profile as compared to HFD rats. Hepatic protection by FO is further substantiated by the normal liver histological findings in HFD fed rats. These data suggest that FO participate in the normal regulation of plasma lipid concentration and cholesterol metabolism in liver. No adverse effect of FO on growth parameters and plasma lipids in rats fed with fat-free diet. The results of the present study demonstrate that FO may be developed as a useful therapy for hyperlipidemia through reducing hepatic lipids, thereby proving its hypolipidemic activity. [Copyright &y& Elsevier]

Genistein (GEN) has been shown to significantly inhibit hepatic triglyceride accretion triggered by estrogen deficiency. The main purpose of this in vitro study was to investigate the function and molecular mechanism of estrogen receptor β (ERβ) in regulating hepatic lipid metabolism induced by GEN. Different doses of GEN or GEN with an ERβ antagonist were treated with HepG2 cells. Results showed that 25 μM GEN significantly diminished triglyceride levels. Meanwhile, GEN downregulated the levels of genes and proteins involved in lipogenesis, such as sterol-regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and stearoyl-coenzyme A desaturase 1 (SCD1), and upregulated the gene and protein levels of the regulation factors responsible for fatty acid β-oxidation, such as carnitine palmitoyltransferase 1α (CPT-1α) and peroxisome proliferator-activated receptor α (PPARα). Furthermore, 25 μM GEN reduced the levels of phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Moreover, most of these effects from GEN were reverted by pretreatment with the antagonist of ERβ. In conclusion, GEN improved hepatic lipid metabolism by activating ERβ and further modulation of Akt/mTOR signals. The results provide novel aspects of the regulatory mechanism of ERβ on hepatic lipid metabolism and might help to profoundly understand the functions of food-derived phytoestrogens in preventing and treating hepatic steatosis in postmenopausal women. [ABSTRACT FROM AUTHOR]

In this study, we investigated the anti-obesity properties of the novel peptide Ala-Gly-Leu-Gln-Phe-Pro-Val-Gly-Arg (AGL9), isolated from the enzymatic hydrolysate of Allomyrinadichotoma larvae. To investigate the preventive effects of AGL9 against hepatic steatosis and its possible mechanisms of action, we established an nonalcoholic fatty liver disease (NAFLD) model by feeding C57BL/6 mice a high-fat diet. NAFLD mice were administered 100 mg/kg AGL9 and 60 mg/kg orlistat via gavage (10 mL/kg) for 5 weeks, followed by the collection of blood and liver tissues. We found that AGL9 normalized the levels of serum alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol, high-density lipoprotein, very low-density lipoprotein (LDL)/LDL, adiponectin, and leptin in these mice. Additionally, AGL9 activated the protein-level expression of 5′ AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation and the transcript-level expression of sterol regulatory element-binding protein-1c, fatty acid synthase, superoxide dismutase, glutathione peroxidase, glucocorticoid receptor, nuclear respiratory factor 2, tumor necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1 in hepatocytes. These results showed that AGL9 exhibited hepatoprotective effects by attenuating lipid deposition, oxidative stress, and inflammation via inhibition of AMPK/Nrf2 signaling, thereby reducing the production of hepatic proinflammatory mediators and indicating AGL9 as a potential therapeutic strategy for NAFLD. [ABSTRACT FROM AUTHOR]

Lipid metabolism disorder plays a fundamental role in the pathogenesis of atherosclerosis. As the largest metabolic organ of the human body, the liver has a key role in lipid metabolism by influencing fat production, fat decomposition, and the intake and secretion of serum lipoproteins. Numerous clinical and experimental studies have indicated that the dysfunction of hepatic lipid metabolism is closely related to the onset of atherosclerosis. However, the identity and functional role of hepatic lipid metabolism responsible for these associations remain unknown. This review presented that cholesterol synthesis, cholesterol transport, and the metabolism of triglycerides, lipoproteins, and fatty acids are all associated with hepatic lipid metabolism and atherosclerosis. Moreover, the roles of gut microbiota, inflammatory response, and oxidative stress in the pathological association between hepatic lipid metabolism and atherosclerosis are also discussed. This significant evidence strongly supports that hepatic lipid metabolism disorders may increase the risk of atherosclerosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

• HFD consumption alteres the expression of genes involved in lipid metabolism. • PGG reduces HFD-mediated body weight gain and hepatic steatosis. • PGG reverses HDF-induced alterations in hepatic lipid metabolic gene expression. • PGG, a well tolerated natural product, holds the potential for NAFLD treatment. Non-alcoholic fatty liver disease (NAFLD) is currently the most frequently occurring liver disorder in the world. However, a specific drug for the treatment of patients with NAFLD is not available. Therefore, the discovery of novel compounds for the treatment of NAFLD and elucidation of the underlying mechanisms of therapeutic drugs that can be used to treat this disease are urgently needed. 1,2,3,4,6 penta- O -galloyl-β- d -glucose (PGG) is known to exert anti-inflammatory, antidiabetic, and hepatoprotective effects. However, little is known about the therapeutic potential of PGG in NAFLD. In this study, we investigated the effects of PGG on a high-fat diet (HFD)-induced mouse model of NAFLD. PGG was co-administered along with an HFD to C57BL/6 mice. After eight weeks of treatment, serum biochemistry, liver steatosis, and lipid metabolism-related genes were examined. The results showed that PGG treatment significantly reduced HFD-induced gain in body weight, liver steatosis, and leukocyte infiltration in a dose-dependent manner. Furthermore, PGG treatment markedly reduced serum triglyceride and glucose levels in HFD mice. Moreover, alterations in the mRNA expression of genes involved in lipid metabolism, including Hmgcr , Acc1 , Abca1 , Mttp , and Cd36 , observed in the livers of HFD-treated mice were significantly reversed by PGG treatment. PGG significantly reduced HFD-induced protein expression of CD36, which is associated with fatty acid uptake, insulin resistance, hyperinsulinemia, and increased hepatic steatosis, in the liver of HFD mice. These results suggest that PGG inhibits HFD-induced hepatic steatosis and reverses HFD-induced alterations of gene expression in lipid metabolism. PGG has been shown to be well tolerated; therefore, it has potential uses in NAFLD treatment. [ABSTRACT FROM AUTHOR]

• Gegen Qinlian Decoction abated nonalcoholic steatohepatitis associated liver injuries. • Gegen Qinlian Decoction could improve lipid metabolism. • Gegen Qinlian Decoction had anti-oxidative stress effect. • Gegen Qinlian Decoction had anti-inflammatory effect. • Anti-inflammatory effect involved inhibition of TLR4 signaling pathways. Gegen Qilian Decoction (GGQLD) is a well-established classic Chinese medicine prescription in treating nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of GGQLD action on NASH is still not clear. This study aimed to assess the anti-NASH effect of GGQLD, and to explore its molecular mechanisms in vivo and in vitro. In HFD-fed rats, GGQLD decreased significantly serum triglyceride (TG), cholesterol (CHO), total bile acid (TBA), low-density lipoprotein (LDL), free fatty acid (FFA) and lipopolysaccharide (LPS) levels, increased levels of differentially expressed proteins (DEPs) Ahcy, Gpx1, Mat1a, GNMT, and reduced the expression of ALDOB. In RAW264.7 macrophages, GGQLD reduced the expression levels of inflammatory factors TNF-α and IL-6 mRNA, and diminished NASH by increasing differentially expressed genes (DEGs) CBS, Mat1a, Hnf4α and Pparα to reduce oxidative stress or lipid metabolism. The results of DEGs verification also showed that GGQLD up-regulated expressions of Hnf4α, Pparα and Cbs genes. In HepG2 cells, GGQLD decreased IL-6 levels and intracellular TG content, and inhibited FFA-induced expression of toll-like receptor 4 (TLR4). In summary, GGQLD abates NASH associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of TLR4 signal pathways. These findings provide new insights into the anti-NASH therapy by GGQLD. [ABSTRACT FROM AUTHOR]

• Disruption of GH-JAK2-STAT5 signalling induces hepatic steatosis. • Hepatic STAT5 executes tumour suppressive functions in HCC development. • Hepatic JAK2 exerts oncogenic functions in HCC development. • Divergent role of GH signalling in oxidative stress and damage management. The rising prevalence of obesity came along with an increase in associated metabolic disorders in Western countries. Non-alcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of the metabolic syndrome and is linked to primary stages of liver cancer development. Growth hormone (GH) regulates various vital processes such as energy supply and cellular regeneration. In addition, GH regulates various aspects of liver physiology through activating the Janus kinase (JAK) 2- signal transducer and activator of transcription (STAT) 5 pathway. Consequently, disrupted GH - JAK2 - STAT5 signaling in the liver alters hepatic lipid metabolism and is associated with NAFLD development in humans and mouse models. Interestingly, while STAT5 as well as JAK2 deficiency correlates with hepatic lipid accumulation, recent studies suggest that these proteins have unique ambivalent functions in chronic liver disease progression and tumorigenesis. In this review, we focus on the consequences of altered GH - JAK2 - STAT5 signaling for hepatic lipid metabolism and liver cancer development with an emphasis on lessons learned from genetic knockout models. [ABSTRACT FROM AUTHOR]

Aerobic exercise is widely accepted as a beneficial option for reducing fat in humans. Recently, it has been suggested that molecular hydrogen (H 2 ) augments mitochondrial oxidative phosphorylation. Therefore, the hypothesis that inhaling H 2 could facilitate lipid metabolism during aerobic exercise was investigated in the current study by measuring the breath acetone levels, which could be used as non-invasive indicators of lipid metabolism. This study aimed to investigate the effect of inhaling H 2 on breath acetone output during submaximal exercise using a randomized, single-blinded, placebo-controlled, and cross-over experimental design. After taking a 20-minute baseline measurement, breath acetone levels were measured in ten male subjects who performed a 60% peak oxygen uptake-intensity cycling exercise for 20 minutes while inhaling either 1% H 2 or a control gas. In another experiment, six male subjects remained in a sitting position for 45 minutes while inhaling either 1% H 2 or a control gas. H 2 significantly augmented breath acetone and enhanced oxygen uptake during exercise (P < 0.01). However, it did not significantly change oxidative stress or antioxidant activity responses to exercise, nor did it significantly alter the breath acetone or oxygen uptake during prolonged resting states. These results suggest that inhaling H 2 gas promotes an exercise-induced increase in hepatic lipid metabolism. The study was approved by the Ethical Committee of Chubu University, Japan (approved No. 260086-2) on March 29, 2018.

Sexual dimorphism is associated not only with somatic and behavioral differences between men and women, but also with physiological differences reflected in organ metabolism. Genes regulated by sex hormones differ in expression in various tissues, which is especially important in the case of liver metabolism, with the liver being a target organ for sex hormones as its cells express estrogen receptors (ERs: ERα, also known as ESR1 or NR3A; ERβ; GPER (G protein-coupled ER, also known as GPR 30)) and the androgen receptor (AR) in both men and women. Differences in sex hormone levels and sex hormone-specific gene expression are mentioned as some of the main variations in causes of the incidence of hepatic diseases; for example, hepatocellular carcinoma (HCC) is more common in men, while women have an increased risk of autoimmune liver disease and show more acute liver failure symptoms in alcoholic liver disease. In non-alcoholic fatty liver disease (NAFLD), the distinction is less pronounced, but increased incidences are suggested among men and postmenopausal women, probably due to an increased tendency towards visceral fat accumulation.

The present study was conducted to evaluate the effects of 3 meals administered daily with varying dietary crude protein (CP) contents on hepatic lipid metabolism with a pig model. Pigs were divided into 3 groups according to the following feeding patterns: feeding a basal CP diet 3 times daily (3C); feeding a high CP diet for breakfast, the basal CP diet for lunch, and a low CP diet for dinner (HCL); and feeding the low CP diet for breakfast, the basal CP diet for lunch, and the high protein diet for dinner (LCH). Three groups took equivalent diet per meal ensuring that every pig was fed with similar dietary formulae daily. Results showed that HCL feeding pattern reduced the relative kidney weight ( P  < 0.05), and LCH feeding pattern increased the relative liver weight of pigs ( P  < 0.05) when compared with those in the 3C group. Plasma urea nitrogen ( P  < 0.01) and lipase ( P  < 0.05) decreased in the HCL group but increased in the LCH group. Both HCL and LCH feeding patterns reduced plasma triglycerides ( P  < 0.01), non-esterified fatty acids (NEFA) ( P  < 0.01), and hepatic crude fat (0.05 <  P  < 0.10) of pigs. Real-time quantitative PCR (RT-qPCR) results showed that dynamic feeding patterns down-regulated ( P  < 0.05) the mRNA level of lipid metabolism related genes, including adipose triglyceride lipase (ATGL) , acetyl-CoA carboxylase ( ACCα ), liver X receptor ( LXRα ) in the liver, and negatively regulate elements of circadian clock, including period 1 ( Per1 ), period 2 ( Per2 ), cryptochrome ( Cry2 ), which in turn, upregulated ( P  < 0.05) the protein expression of positive regulate element brain and muscle Arnt-like 1 (BMAL1) when compared with 3C group. Overall, our findings suggested that dynamic feeding patterns may affect hepatic lipid metabolism via regulation of the circadian clock., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2020 Chinese Association of Animal Science and Veterinary Medicine. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

The liver is the main site of de novo lipogenesis in poultry, and hepatic lipid metabolism disorder will lead to excessive abdominal fat deposition or fatty liver disease, finally causing huge economic loss. The present study was conducted to investigate developmental changes in hepatic lipid metabolism of chicks from embryonic periods to the first week after hatching. Liver samples were collected from embryonic day 11 (E11) to the age of day 7 posthatch (D7) for lipid metabolism analysis. Hematoxylin-eosin and Oil Red O staining analysis showed that hepatic lipids increased gradually during embryonic period and declined posthatch; The sum of hepatic triglycerides and cholesterol reached the peak at E19 and D1 by ELISA analysis (P < 0.05). Acetyl-CoA carboxylase, fatty acid synthase, and acyl-CoA desaturase 1 mRNA expression in the liver were higher from E17 to D1 with the peak at E19 when compared with those at E13 and E15 (P < 0.05). Hepatic elongase of very long-chain fatty acids 6 and microsomal triglyceride transfer protein mRNA abundance were lower during embryonic periods but reached relative higher level after hatching (P < 0.05). On the contrary, hepatic carbohydrate response element binding protein (ChREBP), carnitine palmitoyltransferase 1, and peroxisome proliferators-activated receptor α expression were higher during embryonic periods but decreased posthatch (P < 0.05). The mRNA abundance of sterol-regulatory element binding protein 1c was the lowest at E13 and E15, then increased gradually from E17 to D1, while decreased from D3 to D7 little by little (P < 0.05). In summary, hepatic lipogenesis genes have different expression patterns during the embryonic periods and the first week of posthatch, which might be activated by ChREBP during embryonic periods; fatty acid oxidation was enhanced around the hatched day but declined posthatch. These findings will broaden the understanding of physiological characteristics and dynamic pattern about hepatic lipid metabolism in chicks., (Copyright © 2020. Published by Elsevier Inc.)

Scope: Non-alcoholic fatty liver disease (NAFLD) among adolescents has been related to fructose intake. Additionally, maternal high-fat diet (mHFD) increases the offspring susceptibility to NAFLD at adulthood. Here, it is hypothesized that mHFD may exacerbate the fructose impact in adolescent male rat offspring, by changing the response of contributing mechanisms to liver injury., Methods and Results: Female Wistar rats receive standard (mSTD: 9% fat) or high-fat diet (mHFD: 29% fat) prior mating throughout pregnancy and lactation. After weaning, offspring receive standard chow and, from the 25th to 45th day, receive water or fructose-drinking water (15%). At 46 days old, fructose groups show increased adiposity, increased serum and hepatic triglycerides, regardless of maternal diet. Fructose aggravates the hepatic imbalance of redox state already exhibited by mHFD offspring. The hepatic activation of cellular repair pathways by fructose, such as unfolded protein response and macroautophagy, is disrupted only in mHFD offspring. Fructose does not change the liver morphology of mSTD offspring. However, it intensifies the liver injury already present in mHFD offspring., Conclusion: Fructose intake during adolescence accelerates the emergence of NAFLD observed previously at the adult life of mHFD offspring, and reveals a differentiated hepatic response to metabolic insult, depending on the maternal diet., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Liver has numerous critical metabolic functions including lipid metabolism, which is usually dysregulated in obesity, the metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates bone morphogenetic proteins (BMPs) play an important role in adipogenesis and thermogenic balance in adipogenic progenitors and adipose tissue. However, the direct impact of BMPs on hepatic steatosis and possible association with NAFLD are poorly understood. Here, we found that BMP4 was up-regulated in oleic acid-induced steatosis and during the development of high fat diet (HFD)-induced NAFLD. Exogenous BMP4 reduced lipid accumulation and up-regulated the genes involved in lipid synthesis, storage and breakdown in hepatocytes. Exogenous BMP4 inhibited hepatic steatosis, reduced serum triglyceride levels and body weight, and alleviated progression of NAFLD in vivo . Mechanistically, BMP4 overexpression in hepatocytes down-regulated most components of the mTORC1 signaling axis. Collectively, these findings strongly suggest that BMP4 may play an essential role in regulating hepatic lipid metabolism and the molecular pathogenesis of NAFLD. Manipulating BMP4 and/or mTORC1 signaling axis may lead to the development of novel therapeutics for obesity, metabolic syndrome, and NAFLD.

4-Hydroxy-3-methoxycinnamic acid (HMCA), a hydroxycinnamic acid derivative, is abundant in fruits and vegetables, including oranges, carrots, rice bran, and coffee beans. Several beneficial effects of HMCA have been reported, including improvement of metabolic abnormalities in animal models and human studies. However, its mitigating effects on high-fat diet (HFD)-induced obesity, and the mechanism underlying these effects, remain to be elucidated. In this study, we demonstrated that dietary HMCA was efficacious against HFD-induced weight gain and hepatic steatosis, and that it improved insulin sensitivity. These metabolic benefits of HMCA were ascribable to 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) produced by gut microbiota. Moreover, conversion of HMCA into HMPA was attributable to a wide variety of microbes belonging to the phylum Bacteroidetes. We further showed that HMPA modulated gut microbes associated with host metabolic homeostasis by increasing the abundance of organisms belonging to the phylum Bacteroidetes and reducing the abundance of the phylum Firmicutes. Collectively, these results suggest that HMPA derived from HMCA is metabolically beneficial, and regulates hepatic lipid metabolism, insulin sensitivity, and the gut microbial community. Our results provide insights for the development of functional foods and preventive medicines, based on the microbiota of the intestinal environment, for the prevention of metabolic disorders. [ABSTRACT FROM AUTHOR]

Many studies have shown that resistant maltodextrin (RMD) possesses blood cholesterol lowering and anti-obesity effects. In order to investigate the effect of RMD on lipid metabolism in the liver, rats were fed with a high-fat (HF) diet for 7 weeks to induce hyperlipidemia and fatty liver. Normal control rats were fed with a normal diet. HF-diet-fed rats were treated with 5% RMD for 8 weeks. The results showed that the increased plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, the increased hepatic triglyceride and total cholesterol levels, and fatty liver in HF-diet-fed rats were significantly decreased after supplementation with RMD. Supplementation with RMD significantly (1) induced AMP-activated protein kinase (AMPK) phosphorylation; (2) inhibited the activities of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and HMG-CoA reductase (HMGCR); (3) suppressed the protein expression of peroxisome proliferator activated receptor (PPAR)-γ; (4) increased β-oxidation of fatty acids by increasing the protein expression carnitine palmitoyl transferase 1α (CPT-1α) in the livers of HF-diet-fed rats. Taken together, supplementation of RMD was capable of inhibiting lipogenic enzyme activities and inducing fatty acid β-oxidation through increasing AMPK activation, thereby reducing lipid accumulation in the liver. [ABSTRACT FROM AUTHOR]

Dietary polyunsaturated fatty acids (PUFA), especially n-3 and n-6 fatty acids (FA), play an important role in the regulation of FA metabolism in all mammals. However, FA metabolism differs between different organs, suggesting a distinct partitioning of highly relevant FA. For the present study in cattle, a novel technology was applied to overcome rumen biohydrogenation of dietary unsaturated FA. Angus heifers were fed a straw-based diet supplemented for 8 weeks with 450 g/day of rumen-protected oil, either from fish (FO) or sunflower (SO). The FA composition in blood and five important organs, namely heart, kidney, liver, lung, and spleen, was examined. In blood, proportions of polyunsaturated FA were increased by supplementing FO compared to SO. The largest increase of eicosapentaenoic acid (EPA) proportion was found with FO instead of SO in the kidney, the lowest in the lung. Docosahexaenoic acid (DHA) was increased more in the liver than in kidney, lung, and spleen. The heart incorporated seven times more EPA than DHA, which is more than all other organs and described here for the first time in ruminants. In addition, the heart had the highest proportions of α-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) of all organs. The proportions of polyunsaturated FA in the lung and spleen were exceptionally low compared to heart, liver, and kidney. In conclusion, it was shown that the response to FO in the distribution of dietary n-3 FA was organ-specific while proportions of n-6 FA were quite inert with respect to the type of oil supplemented., (© 2019 AOCS.)

The quality of canola oil is affected by different extraction methods. The effect of cold-pressed canola oil (CPCO) diet and traditional refined bleached deodorized canola oil (RBDCO) diet on lipid accumulation and hepatic steatosis in mice were investigated. The body weight, peroxisome proliferator-activated receptor-α concentration, serum lipid profile, insulin sensitivity, and oxidative stress were increased in mice fed with CPCO diet, which had higher unsaturated fatty acid, tocopherols, phytosterols, and phospholipids but lower saturated fatty acid than RBDCO, after 12 weeks,. Moreover, CPCO significantly increased tocopherols and phytosterols content in liver and reduced liver cholesterol contents and lipid vacuoles accumulation than RBDCO. Also, serum proinflammatory cytokines, 3-hydroxy-3-methylglutary coenzyme A reductase expression level, lipogenic enzymes, and transcriptional factors such as sterol regulatory element-binding proteins 1c, acetyl-CoA carboxylase, and fatty acid synthase in the liver were also markedly downregulated from CPCO diet mice. Overall, CPCO can reduce lipid accumulation and hepatic steatosis by regulating oxidative stress and lipid metabolism in Kun Ming mice compared with RBDCO. PRACTICAL APPLICATION: The results suggested that more bioactive components were contained in cold-pressed canola oil (CPCO) rather than refined bleached deodorized canola oil (RBDCO). CPCO could lower the risk of obesity and hyperlipidemia, reduce lipid accumulation, and prevent hepatic steatosis. It could be considered as a kind of better edible oil than RBDCO., (© 2019 Institute of Food Technologists®.)

A novel AMP-activated protein kinase (AMPK) activator, IMM-H007 (H007), has been reported to reduce serum lipid levels and inhibit lipid accumulation in the liver in hyperlipidemic animal models. However, how H007 ameliorates hepatic steatosis and inflammation remains unknown. In the present study, H007, at 200 mg/kg, reduced hepatic lipid levels and the levels of collagenous fiber in the liver in high-fat diet (HFD)-fed hamsters compared to those in the HFD group. Meanwhile, compared to the controls, H007 significantly inhibited sterol-regulatory element binding protein (SREBP)-1c and acetyl CoA carboxylase (ACC) expression by upregulating the AMPK activity, suppressing the saturated fatty acid accumulation and increasing polyunsaturated fatty acid synthesis in the liver. Compared to the controls, H007 treatment inhibited the expression of monocyte chemotactic protein (MCP-1) in fatty acid-treated HepG2 cells; suppressed leukocyte adherence and rolling on the liver microvasculature; and suppressed hepatic macrophage infiltration. H007 also suppressed the expression of nuclear factor-κB (NF-κB) p65 in fatty acid- and lipopolysaccharide-treated HepG2 cells compared to that in the controls by activating AMPK. These data suggested that H007 had a beneficial effect by improving the lipid composition in the liver and inhibiting inflammatory cell trafficking in the development of nonalcoholic fatty liver disease., (Copyright © 2019 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Two trials were performed using extruded diets as on-growing feeds for weaned Atlantic bluefin tuna (Thunnus thynnus; ABT) to establish adequate dietary levels of both lipid and omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), and impacts on lipid metabolism via liver gene expression. In trial A, ABT were fed with either a commercial feed (Magokoro®; MGK) as a reference diet or two experimental feeds differing in lipid levels (15 or 20%) using krill oil (KO) as the single lipid source in order to estimate suitable lipid content. Fish fed MGK displayed the highest growth, followed by 15KO, and therefore a dietary lipid content of 15% was considered preferable to 20% at this stage. In trial B, fish were fed MGK, 15KO, or a feed containing 15% lipid with a blend of KO and rapeseed oil (RO) (1:1, v/v; 15KORO). Fish fed 15KO and 15KORO showed no difference in weight gain, specific growth rate, and fork length. Increasing dietary lipid level or including vegetable oil, RO, in the feeds did not increase liver lipid content. Liver fatty acid compositions largely reflected dietary profiles confirming very limited endogenous LC-PUFA biosynthesis. Liver of ABT fed 15KO and 20KO displayed the highest contents of docosahexaenoic acid (DHA). The hepatic expression of genes encoding enzymes and transcription factors involved in lipid and fatty acid metabolism, as well as genes encoding antioxidant enzymes, showed that many of these genes were regulated by dietary lipid and LC-PUFA content. Results suggested that ABT juveniles can be on-grown on inert dry feeds that support good fish growth and the accumulation of DHA.

Background: Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursodeoxycholic acid (UDCA) play an essential role in the pathogenesis of NAFLD by regulating the level of sterol regulatory element-binding protein (SREBP) 1c, but the underlying regulatory mechanism remains elusive. Increased evidence indicates that the AKT/mTOR/SREBP-1 signaling pathway is a key pathway to regulate hepatic cellular lipid metabolism. UDCA may regulate the AKT/mTOR/SREBP-1 signaling pathway to ameliorate hepatic lipid metabolism., Aim: To investigate the functional mechanism of UDCA in an oleic acid (OA)-induced cellular model of NAFLD., Methods: The cellular model of NAFLD was established using OA and treated with UDCA. First, the best concentration of UDCA was selected. For the best time-dependent assay, cells were stimulated with OA only or co-treated with OA and 2 mmol/L UDCA for 24 h, 48 h, and 72 h. Oil red O staining was used to observe the accumulation of intracellular lipids, while the intracellular contents of triglyceride, alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and aspartate aminotransferase (AST) were detected by enzymatic methods. Meanwhile, the expression levels of AKT/mTOR/SREBP-1 signaling pathway-related proteins were detected by real-time PCR and Western blot., Results: In the NAFLD cell model established with LO2 cells induced using OA, lipid accumulation was obvious. UDCA significantly inhibited lipid accumulation at different concentrations (especially 2 mmol/L) and decreased cell growth ability at different time points. The biochemical parameters like ALT, AST, and GGT were significant improved by UDCA. UDCA treatment vividly repressed the activation of AKT, mTOR, and CRTC2 and the expression of nSREBP-1 in LO2 cells induced with OA., Conclusion: Our findings demonstrate the effect of UDCA in improving NAFLD. UDCA attenuates OA-induced hepatic steatosis mainly by regulation of AKT/mTOR/SREBP-1 signal transduction., Competing Interests: Conflict-of-interest statement: There is no conflict of interest in this study.

Simple steatosis is the hallmark of nonalcoholic fatty liver disease, with lipid accumulating as either microvesicular or macrovesicular lipid droplets within hepatocytes. The present study used a combination of laser capture microdissection and RNAseq to characterize murine gene expression in nonsteatotic, microsteatotic, and macrosteatotic compartments collected from the same liver. The data indicate that microvesicular steatosis is intermediate to macrovesicular steatosis, showing a widespread and pronounced metabolic gene regulation of lipid export, gluconeogenesis, and de novo lipogenesis. Key enzymes, such as fatty acid synthase and fructose 1,6-bisphosphatase as well as apolipoprotein C-III, were identified to show clear expression differences between the compartments. Furthermore, increased expression of lipid particle formation genes provided a molecular description of the fusion of microsteatotic lipid compartments to produce macrosteatotic cells with a single enlarged lipid droplet., (© 2019 AOCS.)

Background: As a promising nanocarrier in biomedical fields, silica nanoparticles (SiNPs) could transfer from the circulatory system to multiple organs. Among these, blood-liver molecular exchange is a critical factor in biological response to NPs. However, the potential effect of SiNPs on hepatic lipid metabolism is unclear. In this study, we employed three models to attempt discover whether and how SiNPs disturb hepatic lipid metabolism in vivo and in vitro., Methods: Firstly we used ICR mice models to evaulated the effects of SiNPs on the serum and hepatic lipid levels through repeated intravenous administration, meanwhile, the protein expressions of protein markers of lipogenesis (ACC1 and FAS), the key enzyme of fatty acid β-oxidation, CPT1A,and leptin levels in liver were detected by western blot. For verification studies, the model organism zebrafish and cultured hepatic L02 cells were further performed. The TLR5 and adipocytokine-signaling pathway were verified., Results: Inflammatory cell infiltration and mild steatosis induced by SiNPs were observed in the liver. Cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were elevated significantly in both blood serum and liver tissue, whereas the ratio of high-density:low-density lipoprotein cholesterol was markedly decreased. Protein markers of lipogenesis (ACC1 and FAS) were elevated significantly in liver tissue, whereas the key enzyme of fatty acid β-oxidation, CPT1A, was decreased significantly. Interestingly, leptin levels in the SiNP-treated group were also elevated markedly. In addition, SiNPs caused hepatic damage and steatosis in zebrafish and enhanced hyperlipemia in high-cholesterol diet zebrafish. Similarly, SiNPs increased the release of inflammatory cytokines (IL1β, IL6, IL8, and TNFα) and activated the TLR5-signaling pathway in hepatic L02 cells., Conclusion: In summary, our study found that SiNPs triggered hyperlipemia and hepatic steatosis via the TLR5-signaling pathway. This suggests that regulation of TLR5 could be a novel therapeutic target to reduce side effects of NPs in living organisms., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Dysbiotic gut microbiota contributes to genetically obese phenotype in human. However, the effect of genetic obesity-associated gut microbiota on host hepatic metabolic deteriorations remains largely unknown. Gut microbiota from a genetically obese human donor before and after a dietary weight loss program was transplanted into germ-free C57BL/6J male mice, grouped as PreM and PostM groups, respectively. The gut microbiome, liver pathology and transcriptome response in the gnotobiotic mice were evaluated. After being fed on normal chow diet for 4 weeks, PreM group developed liver macrovesicular steatosis accompanied with higher concentrations of hepatic triglyceride and cholesterol, while PostM group exhibited normal hepatic physiology. The gut microbiota in PreM and PostM groups was significantly different from each other and was more resembling with their respective donor. RNA-sequencing revealed that, in comparison with PostM group, PreM group showed a foregoing pro-steatotic transcriptional response in liver featuring by the repression of lipid beta-oxidation and the activation of lipid absorption and cholesterol uptake before the pathology of liver steatosis. Moreover, peroxisome proliferator-activated receptor alpha (PPARα), which was repressed in PreM group, may act as crucial regulator of the hepatic transcriptional profile of lipid metabolism between two groups. Our results show that gut microbiota from a genetically obese human promotes the onset of liver steatosis by impacting hepatic transcriptional profile of lipid metabolism in mice. This adds new evidence that gut microbiota may play a causative role in the development of non-alcoholic fatty liver disease.