Expression Of ACC Research Articles

Yogurt-derived Lactobacillus plantarum Q16 alleviated high-fat diet-induced non-alcoholic fatty liver disease in mice

Accumulating evidence revealed that some probiotics regulated lipid metabolism and alleviated diet-induced non-alcoholic fatty liver disease (NAFLD). This study mainly explored whether yogurt-derived Lactobacillus plantarum Q16 modulated lipid and energy metabolism, and suppressed microbial dysbiosis in high-fat diet (HFD)-fed mice. Results showed that oral administration of L. plantarum Q16 improved serum and hepatic lipid profile. Protein analysis showed that L. plantarum Q16 could reduce hepatic lipid content by reducing the expression of FAS, ACC, SCD-1, Srebp-1c and ATGL, but increasing expression levels of CPT-1α, PPAR-α and ATGL. Meanwhile, L. plantarum Q16 also improved hepatic energy metabolism by regulating FGF21/adiponectin/AMPKα/PGC-1α signaling pathway. Metagenomic analysis also discovered that L. plantarum Q16 increased species diversity and richness of intestinal microbiota, promoted proliferation of beneficial commensals and suppressed the growth of endotoxin-producing microorganisms in the colon of HFD-fed mice. Overall, L. plantarum Q16 protected against HFD-induced NAFLD by improving hepatic profile and regulating colonic microbiota composition.

238-LB: Erythropoietin Receptor–Mediated Erythropoietin Regulation of Energy Metabolism in Mice

EPO receptor (EPOR) expression in white adipose tissue (WAT) mediates EPO metabolic activity and mitochondrial biogenesis. Mice that lack EPOR in adipose tissue have increase fat mass accumulation, increased susceptibility to diet induced obesity and decreased WAT mitochondrial activity. Here we assess the potential for EPO to promote a metabolic response in liver, brown adipose tissue and skeletal muscle by assessing the extent of EPOR expression using the EpoR-dtTomato-Cre mouse. We quantified EPOR in liver, brown adipose tissue and soleus muscle compared with EPOR expression in subcutaneous and epididymal WAT and found the highest level in WAT by mRNA, protein and immunohistochemical analyses. Elevated EPO by intraperitoneal injection or by transgene over expression resulted in tissue specific changes in gene expression. In liver, EPO decreased expression of genes involved in gluconeogenesis and triglyceride secretion. In brown adipose tissue, EPO increased expression of thermogenic genes. In subcutaneous WAT, EPO decreased genes involved in lipogenesis. In soleus muscle, EPO decreased expression of lipolytic genes. These findings indicate that increased EPO decreases lipogenesis gene LPI, ACC1, ACC2 and Fas expression in the BAT, skeletal muscle, ScWAT, liver and eWAT and increases lipolysis gene Atgl and Hsl expression in the BAT, ScWAT, skeletal muscle, and Atgl expression in the liver and eWAT. Measurements of energy metabolism did not detect any changes associated with EPO treatment in energy expenditure, respiratory exchange ratio, locomotor activity and total activity. However, as observed in WAT, we also find that EPO promotes mitochondria activity in liver, brown adipose tissue and skeletal muscle indicated by elevated gene expression of CytC, Idh3α, Cpt1, Pgc-1α and Cox7a1. Together, these data support the hypothesis that EPO promotes lipolysis and inhibits fat synthesis to regulate body weight and fat mass. In addition, EPO may regulate glucose metabolism via inhibition of gluconeogenesis. Disclosure W. Yin: None. H. Rogers: None. P. K. Rajvanshi: None. X. An: None. M. Gassmann: None.

Estrogen receptor α activation modulates the gut microbiome and type 2 diabetes risk factors.

Estradiol and exercise can decrease risk factors associated with type 2 diabetes (T2D) including total body weight gain and abdominal fat gain. Estradiol functions through estrogen receptor (ER) α and ERβ. Some studies suggest that activation of ERα may provide protection against T2D. Female Wistar rats were ovariectomized and fed a high‐fat diet for 10 weeks and divided into the following 5 experimental groups: (1) no treatment (control), (2) exercise, (3) estradiol, (4) propylpyrazoletriyl (a selective ERα agonist), and (5) diarylpropionitrile (a selective ERβ agonist). ERα activation decreased the abundance of Firmicutes, and ERα and ERβ activation increased the abundance of Bacteroidetes. ERα activation decreased food consumption, and ERα and ERβ activation increased voluntary activity. Exercise was the only treatment to decrease the blood glucose and serum insulin levels. ERα activation, but not ERβ, increased hepatic protein expression of ACC and FAS and decreased hepatic protein expression of LPL. ERα activation also decreased hepatic mRNA expression of PPARα and PPARγ. This study elucidates the functions of estradiol by assessing specific activation of ERα and ERβ. As obesity increases the abundance of Firmicutes and decreases the abundance of Bacteroidetes, our study shows that ERα activation can restore the gut microbiome to non‐obese abundances. This study further provides novel insights into ERα’s role in hepatic fat metabolism via regulation of ACC, FAS, LPL, PPARα, and PPARγ.

Oxidation-reduction potential affects medium-chain fatty acid ethyl ester production during wine alcohol fermentation

The medium-chain fatty acid ethyl esters (MCFAEEs) are a group of important aroma compounds generated during wine production. Wine alcohol fermentation involves several redox processes, which are affected by the oxidation–reduction potential (ORP). However, the mechanism via which ORP regulates MCFAEE production remains unclear. To investigate the effect of ORP on MCFAEE production, wine alcohol fermentation was performed using Saccharomyces cerevisiae under different ORPs. The results demonstrated that the ORPs studied (except for 90 mV) did not significantly affect cell growth, sugar consumption, and ethanol production, while the MCFAEE concentration in the simulated wines can be manipulated by ORP operation. MCFAEE levels increased till 96 h, and then decreased. The maximum MCFAEE level of 1222.97 μg/L was obtained after 96 h at 0 mV, which was 45.32% higher than that of the control. During the increase, higher relative expression of ACC1, FAS1, FAA2 and EEB1, elevated external citric acid flux, and moderate intracellular NADP+/NADPH ratio were observed at 0 mV compared to that at other ORPs. During the decrease, lowest relative expression of POX1 was detected at 0 mV. We showed for the first time the relationship between ORP operation and MCFAEE production in winemaking, which will improve the aroma quality of wine.

The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production.

3-Hydroxypropionic acid (3-HP) is a promising high value-added chemical. Acetyl-CoA carboxylase (Acc) is a vital rate-limiting step in 3-HP biosynthesis through the malonyl-CoA pathway. However, Acc toxicity in cells during growth blocks its ability to catalyze acetyl-CoA to malonyl-CoA. The balancing of Acc and malonyl-CoA reductase (MCR) expression is another an unexplored but key process in 3-HP production. To solve these problems, in the present study, we developed a method to mitigate Acc toxicity cell growth through Acc subunits (AccBC and DtsR1) expression adjustment. The results revealed that cell growth and 3-HP production can be accelerated through the adjustment of DtsR1 and AccBC expression. Subsequently, the balancing Acc and MCR expression was also employed for 3-HP production, the engineered strain achieved the highest titer of 6.8 g/L, with a high yield of 0.566 g/g glucose and productivity of 0.13 g/L/h, in shake-flask fermentation through the malonyl-CoA pathway. Likewise, the engineered strain also had the highest productivity (1.03 g/L/h) as well as a high yield (0.246 g/g glucose) and titer (up to 38.13 g/L) in fed-batch fermentation, constituting the most efficient strain for 3-HP production through the malonyl-CoA pathway using a cheap carbon source. This strategy might facilitate the production of other malonyl-CoA-derived chemical compounds in the future.

The Bile Acid Receptor Tgr5 and High Fat, High Sugar‐Induced Liver Injury

BackgroundProgression of fatty liver disease to NASH/fibrosis is a major health concern. Bile acids regulate metabolic homeostasis and inflammation in the liver and gut via the activation of nuclear farnesoid‐X‐receptor (Fxr) and the membrane G protein‐coupled bile acid receptor 1 (Gpbar1, aka Tgr5). Tgr5 is expressed in the gut and skeletal muscle, and in cholangiocytes and Kupffer cells of the liver. Activation of Tgr5 reduces inflammation through suppression of NFκB. Tgr5 also induces GLP‐1 secretion from enterocytes to improve insulin sensitivity. Here, we fed Tgr5‐/‐ mice a high fat, high fructose, and high sucrose diet to test the hypothesis that lack of Tgr5 would exacerbate the progression from fatty liver to NASH/fibrosis.MethodsFemale C57Bl/6J control wild type mice (WT) and Tgr5 knockout mice (Tgr5‐/‐) were fed a high fat (40% kcal), high fructose diet + 20% sucrose water (HFS) for 20 weeks. Metabolic phenotypes were characterized through examination of lipid and cholesterol metabolism pathways, and fibrosis and inflammation pathways.ResultsTgr5‐/‐ mice fed HFS were more glucose intolerant compared to WT mice, despite gaining the same amount of weight. Tgr5‐/‐ mice fed HFS accumulated significantly more hepatic cholesterol and triglycerides compared to WT mice on the same diet, and gene expression of Acc and Fasn were significantly upregulated. Surprisingly, hepatic expression of genes involved in inflammation and fibrosis were significantly reduced in Tgr5‐/‐ mice fed HFS diet. Tgr‐/‐mice had significantly reduced expression of Col1a1, Col1a2, Tgfb, and Sma. Tgr5‐/‐ also had significantly reduced liver hydroxyproline, a measure of collagen production. Liver fibrosis is partly mediated through serotonin signaling. Tgr5‐/‐mice had significantly reduced expression of Maoa and the serotonin receptors Htr2a and Htr2b, which may have protected against the development of liver fibrosis in these mice.ConclusionAltered serotonin metabolism may protect Tgr5‐/‐ mice from the progression of steatosis to NASH/fibrosis induced by a high fat, high sugar diet.

Dietary calcium pyruvate could improve growth performance and reduce excessive lipid deposition in juvenile golden pompano (Trachinotus ovatus) fed a high fat diet.

Excessive lipid deposition in farmed fish is a challenge in the aquaculture industry. To study the effect of dietary calcium pyruvate (CaP) on lipid accumulation in fish, we used a high fat diet (HFD) to establish a lipid accumulation model in juvenile golden pompano (Trachinotus ovatus) and supplemented with 0%, 0.25%, 0.50%, 0.75% and 1.0% CaP (diets D0-D4, respectively). After 8-week feeding in floating cages, dietary CaP significantly improved growth performance, which peaked in fish fed diet D3. Supplementation of CaP significantly decreased whole body lipid content in fish fed D2-D4 and hepatosomatic index and liver lipid content in fish fed D3 and D4. Serum and hepatic antioxidant indices, including glutathione, catalase and superoxide dismutase, showed generally increasing trends in fish fed diets with CaP. In addition, increasing dietary CaP increasingly reduced hepatic activities of hexokinase, phosphofructokinase and pyruvate kinase involved in glycolysis, and increased glycogen contents of the liver and muscle. Dietary CaP up-regulated the liver mRNA expression of pparα, cpt1, hsl and fabp1, but down-regulated expression of srebp-1, fas and acc. In conclusion, 0.75% CaP improved growth performance and reduced excessive lipid deposition by affecting fatty acid synthesis and lipolysis in juvenile T. ovatus fed HFD.

Effects of dietary supplementation of trans-anethole on the intestinal antioxidant status, immune function, and liver lipid metabolism in broilers

This study was aimed to investigate the effects of trans-anethole (TA) on intestinal antioxidant status, immune function and liver lipid metabolism in broilers. A total of 256 1-day-old Arbour Acres broilers were allocated to 4 treatment groups with 8 birds per replicate. TA was added to diets at a concentration of 0 (control), 400, 600, and 800 mg/kg for 42 days. Dietary supplementation of TA increased the average daily feed intake (ADFI) of birds throughout the entire period. TA supplemented at 400 mg/kg of diet contributed to the lowest jejunal and ileal malondialdehyde (MDA) concentration on d 42, and the highest ileal total superoxide dismutase (T-SOD) activity on d 21 and d 42. TA supplementation at the concentration of 400 and 600 mg/kg of diet increased mRNA expression of ileal interleukin (IL)-4 on d 21, and intestinal secretory immunoglobulin A (sIgA) concentration on d 42. Supplementation of TA at the concentration up to 800 mg/kg of diet had adverse effects on intestinal antioxidant status, immune function and liver lipid metabolism compared with control group. Differently, TA supplemented at 400 mg/kg led to lower mRNA expression of liver ACC1, FASN, sterol regulatory element-binding protein 1c (SREBP-1), and higher CPT1 on d 42. In conclusion, TA inclusion improved intestinal antioxidant status and immune function, and enhanced liver lipid metabolism of broilers. HIGHLIGHTS Supplementation of 400 mg/kg of TA increased intestinal antioxidant status and immune function, and promoted liver lipid metabolism of broilers compared with non-supplemented group.

Effect of Lactobacillus fermentum HFY06 Combined with Arabinoxylan on Reducing Lipid Accumulation in Mice Fed with High-Fat Diet.

In this experiment, a high-fat diet was used to induce hyperlipidemia in mice to determine the synergistic effect of AX and L. fermentum HFY06 on the prevention of hyperlipidemia and its potential regulatory mechanism. The results of this study showed that after the AX and L. fermentum HFY06 synergistic intervention, the body weight, epididymal fat index, blood lipid level, and liver function indexes of mice were improved. In addition, the synbiotics comprising AX and L. fermentum HFY06 increased the CAT activity in the serum of mice on a high-fat diet, reduced NO and MDA levels, and improved the body's oxidative stress. From the perspective of molecular biology, on the one hand, AX and L. fermentum HFY06 synergistic intervention activated the AMPK pathway to regulate body lipid metabolism; up-regulated the mRNA expressions of CPT-1, PPAR-α, CYP7A1, and HSL; and down-regulated the mRNA expressions of ACC, C/EBPα, and LPL. On the other hand, the synergistic effect of AX and HFY06 enhanced the mRNA expressions of ZO-1, occludin, and claudin-1 in the small intestine of mice, increased the strength of the intestinal barrier, and optimized the composition of the intestinal microbiota. From the above results, it can be concluded that AX and L. fermentum HFY06 have a synergistic effect in improving hyperlipidemia. However, this study was only performed using animal models, and the lipid synthesis and metabolism mechanism are complicated; hence, further clinical studies are needed.

G protein-coupled estrogen receptor 1 mediates proliferation and adipogenic differentiation of goat adipose-derived stem cells through ERK1/2-NF-κB signaling pathway.

Adipose tissue formation and moderate fat deposition are important for the production performance and eating quality of livestock meats. The self-renewal and adipogenic differentiation of adipose-derived stem cells are responsible for the formation and development of adipose tissue. In addition, estrogen targeting G protein-coupled estrogen receptor 1 (GPER1) has been reported to modulate cell proliferation and differentiation during tissue and organ development. However, the potential correlation among estrogen, GPER1, proliferation, and adipogenic differentiation in goat adipose-derived stem cells (gADSCs) is still unclear. Herein, we demonstrated that 17β-estradiol enhances the proliferative ability of gADSCs, indicated by the increased cell number and cell viability, accompanied by up-regulated expressions of cyclin D1 and PCNA. Meanwhile, the adipogenic differentiation is promoted by 17β-estradiol, supported by higher ccumulation of intracellular lipids and increased expressions of PPARγ, ACC, and FABP4. Notably, these activities are all obviously reduced by administration with GPER1 antagonist G15, but GPER1 agonist G1 enhances cell proliferation and adipogenic differentiation. Moreover, GPER1 silencing diminishes cell proliferation and adipogenic differentiation. In parallel, 17β-estradiol elevates the protein level of nuclear p-p65. Furthermore, the phosphorylation of p65 is enhanced by G1 but inhibited by G15 and GPER1 silencing. In addition, the phosphorylation of p65 is mediated by ERK1/2, suggesting that estrogen targeting GPER1 regulates cell proliferation and adipogenic differentiation of gADSCs through the ERK1/2-NF-κB signaling pathway. This study may provide a strong theoretical basis for improving meat quality, flavor, and cold resistance of livestock.

Transcriptome analysis revealing the mechanism of soybean protein isolates and soybean peptides on Lacticaseibacillus rhamnosus Lra05

To further investigate the promoting effect of soybean protein and peptides on Lacticaseibacillus rhamnosus Lra05 (L. rhamnosus Lra05), the overall changes of gene expression of it was investigated through transcriptome analysis treated with dPEP and dSPI The results showed that there were 890, 113, and 1073 differentially expressed genes (DEGs) in dPEP/MRS, dSPI/MRS and dPEP/dSPI comparison, respectively. Besides, we found dPEP could promote the expression of acc and fab family genes related to fatty acid biosynthesis, but dSPI played the opposite role. Moreover, dPEP stimulated genes clustered in pur family and ribosome protein, responsible for purine and protein synthesis. Interestingly, dPEP suppressed genes regulating peptides and amino acids transportation and dSPI specially inhibited the pyr family genes involved in pyrimidine metabolism. These data revealed the knowledge about the metabolic pathways affected by dPEP and dSPI and provide a preliminary understanding of the relationship between soybean proteins and peptides and L. rhamnosus Lra05.

Hesperidin attenuates hepatic lipid accumulation in mice fed high-fat diet and oleic acid induced HepG2 via AMPK activation

AimsIn recent years, more and more people are suffering from lifestyle-related disease such as nonalcoholic fatty liver disease (NAFLD) because of unhealthy diet and lack of physical exercise. Hesperidin (HDN) is a flavonoid found in high concentrations in citrus fruits. In this study, we investigated the effect of HDN on NAFLD, providing information to develop dietary supplements for NAFLD treatment and prevention. Materials and methodsTesting kits, hematoxylin–eosin staining, oil red O staining, western blot, immunofluorescence, cck-8 assay, and blood biochemical analysis were carried out during the experiments in vivo and in vitro. Key findingsThe current study revealed that HDN significantly reduced liver index and serum lipid levels, and protected against liver steatosis and injury induced by HFD. In addition, HDN suppressed oil acid induced intracellular lipid accumulation in HepG2 cells. Moreover, HDN increased the expression level of pAMPK and downregulated SREBP-1C, ACC and FAS expression in vivo and in vitro. SignificanceIn summary, HDN attenuates lipid accumulation in vivo and in vitro via AMPK activation, suggesting that HDN may serve as a potential therapeutic agent for treating NAFLD.

Heat-Killed Enterococcus faecalis EF-2001 Attenuate Lipid Accumulation in Diet-Induced Obese (DIO) Mice by Activating AMPK Signaling in Liver.

To explore the inhibitory mechanism of heat-killed Enterococcus faecalis, EF-2001 on hepatic lipid deposition, a diet-induced obese (DIO) animal model was established by high-fat diet (HFD). The DIO C57BL/6 mice were divided into four groups: the normal group without HFD (ND, n = 8), obesity group (HFD, n = 8), experimental group (HFD + EF-2001, 200 mg/kg, n = 8), and positive control group (HFD + Orlistat, 60 mg/kg, n = 8). After 4 weeks, liver and adipose tissue were fixed in 10% paraformaldehyde, followed by embedding in paraffin for tissue sectioning. The differences in body mass, body fat ratio, fatty cell area, and lipid profiling of the liver (TC, LDL, and HDL) were also determined. Moreover, Western blot was performed to analyze the expression of lipid accumulation-related proteins, including AMPK, PPARγ, SREBP-1, ACC, and FAS. Compared with the HFD group, the HFD + EF-2001 group exhibited decreased fat mass, liver index, adipocyte area, TC, and LDL, and an increased level of HDL. The results of liver hematoxylin and eosin (H&E), and oil red O staining showed that the mice in each intervention group were improved on hepatic lipid accumulation, and the mice in the HFD + EF-2001 group were the most similar to those in the normal group when compared with the HFD group. From the Western blot results, we proved that EF-2001 activated the AMPK signaling pathway. EF-2001 significantly upregulated the expressions of p-AMPK and p-ACC and downregulated PPARγ, SREBP-1, and FAS in murine liver. Taken together, these results suggest that EF-2001 decrease lipid accumulation in the DIO model mice through the AMPK pathway and ameliorate liver damage by HFD.

Oral Administration of Bacterial β Cell Expansion Factor A (BefA) Alleviates Diabetes in Mice with Type 1 and Type 2 Diabetes.

Diabetes mellitus (DM) is a group of metabolic diseases, and there is an urgent need to develop new therapeutic DM oral drugs with fewer side effects and sound therapeutic efficacy. In this study, a β cell expansion factor A (BefA) production strain of Escherichia coli (BL21-pet 28C-BefA) was constructed, and the antidiabetes effect of BefA was evaluated using type 1 DM (T1DM) and type 2 DM (T2DM) mice models. The T1DM mice results indicated that BefA significantly reduced blood glucose levels; exerted a protective effect on islet β cell morphology; downregulated the expressions of TLR-4, p-NFκB/NFκB, and Bax/Bcl-2, and the secretion levels of IL-1β and TNF-α; increased the expression of PDX-1 protein and insulin secretion in a concentration-dependent manner; and restored the disturbed microbial diversity to normal levels. Similarly with the T1DM mice, BefA obviously increased islet β cells and reduced the inflammatory reaction and apoptosis in T2DM mice, as well as improved liver lipid metabolism by downregulating the expressions of CEBP-α, ACC, and Fasn; inhibited the synthesis of triglycerides; and induced Cpt-1, Hmgcs2, and Pparα in a concentration-dependent manner. In conclusion, BefA alleviates diabetes via increasing the number of islet β cells, reducing the inflammatory reaction and apoptosis, improving liver lipid metabolism, and restoring microbial diversity to normal levels, which provides a new strategy for a DM oral drug.

Exploring the Possible Link between the Gut Microbiome and Fat Deposition in Pigs.

Excessive lipid accumulation and high oxidative stress have become a serious health and economic problem in the pig industry. Fatness characteristics are crucial in pig production since they are closely related to meat quality. The gut microbiome is well acknowledged as a key element in fat deposition. But the link between gut microbiota and fat accumulation in pigs remains elusive. To examine whether there is a link between pigs' gut microbiome, lipogenic properties, and oxidative stress, we selected 5 high-fat pigs and 5 low-fat pigs from 60 250-day-old Jinhua pigs in the present study and collected the colon content, serum sample, and liver and abdominal fat segments from each pig for metagenomic analysis, the oxidative stress assay, and RT-qPCR analysis, respectively. The backfat thickness and fat content of the longissimus dorsi muscle were considerably higher in the high-fat pigs than in the low-fat pigs (P < 0.05). An obvious difference in GSH-Px and MDA in the serum between the high- and low-fat pigs was observed. After RT-qPCR analysis, we found the gene expression of ACC1 and SREBP1 in the liver and FAS, PPARγ, and LPL in the abdominal fat were significantly higher in high-fat pigs than in low-fat pigs (P < 0.05). Additionally, metagenomic sequencing revealed that high-fat pigs had a higher abundance of Archaeal species with methanogenesis functions, leading to more-efficient fat deposition, while low-fat pigs had higher abundances of butyrate-producing bacteria species that improved the formation of SCFAs, especially butyrate, thus alleviating fat deposition in pigs. Furthermore, a total of 17 CAZyme families were identified to give significant enrichments in different fat phenotypes of pigs. This study would provide a detailed understanding of how the gut microbiome influences fat deposition in pigs, as well as a hint for improving growth performance and fatness traits by manipulating the gut microbiome.

High Fat Diet and Ethanol-Induced Fatty Liver Disease Mouse Model

Abstract A diet high in fat and/or alcohol is a major cause of fatty liver disease (FLD), which is a common precursor to chronic liver disease. As the pathogenetic mechanisms of FLD remain unclear, an appropriate animal model is critical to problem solving in this field. This study aimed to develop an FLD mouse model using a diet high in fat and/or ethanol. Five-week-old female ICR mice were given free access to a high fat diet (HFD, 60 kcal % fat of total food), or daily intragastrically administered ethanol (E, 0.5 g/kg/day), or a combination of HFD and ethanol (HFD+E). Hepatic histology was observed with oil red O (ORO) staining. Hepatic triglyceride (TG) levels, antioxidant enzyme activities, and mRNA expression levels of metabolic, antioxidant, and inflammatory genes, i.e. peroxisome proliferator activated receptor-alpha and gamma (Ppar-α and Ppar-γ), sterol regulatory element binding protein-1 (Srebp-1), acetyl-CoA carboxylase (Acc), fatty acid synthase (Fas), fat cluster of differentiation (Cd-36), catalase (Cat), superoxide dismutase 1 and 2 (Sod1 and Sod2), glutathione peroxidase (Gpx), nuclear factor-kappa b (Nf-ĸb), tumor necrosis factor-alpha (Tnf-α), and monocyte chemoattractant protein-1 (Mcp-1) were determined. HFD+E induced FLD in mice by increasing hepatic TG levels and expression of Acc and Fas metabolic genes and Cd-36 and Mcp-1 inflammatory genes, while simultaneously reducing the activity and expression of antioxidant enzymes. These findings confirm that HFD+E is a potent regimen for FLD induction in mice. Keywords: High fat diet, Alcohol, Non-invasive, Antioxidation, Metabolic gene, Inflammatory gene

Effects of different lipid sources on growth performance, fatty acids composition in tissue and expression of genes related to lipid metabolism in largemouth bass (Micropterus salmoides)

An eight-week feeding trial was conducted to investigate the effects of dietary lipid sources on growth performance, fatty acids composition in tissue and expression of genes related to lipid metabolism in juvenile largemouth bass (Micropterus salmoides). Four experimental diets were formulated to contain 6% coconut oil (CO), rapeseed oil (RO), linseed oil (LO) and fish oil (FO), respectively. Each diet was fed to triplicate groups of juvenile for 8 weeks. The results indicated that final body weight (FBW), percent weight gain (PWG), specific growth rate (SGR), feed efficiency (FE), survival, hepatopancreas index (HSI), viscerosomatic index (VSI) and intraperitoneal fat ratio (IPF) were not significantly influenced by dietary different lipid sources (P＞0.05). Moreover, proximate composition in whole body, dorsal muscle and liver were also not significantly affected by dietary different lipid sources (P ＞0.05). Fish fed with FO diet was significantly higher MDA concentration in hepatic and serum than those fed with CO, RO and LO diets (P < 0.05). However, T-AOC, SOD and GSH activities in hepatic and serum were not affected by different lipid sources (P＞0.05). Fish fed with RO diet had significantly higher relative expression of fas and acc in liver than those fed the other diets, the highest expression of lpl was occurred at fish fed with CO diet (p < 0.05). Meanwhile, fish fed with CO and FO diets had significantly lower expression of elovl5 and Δ6fad in liver than those fed with RO diet (p < 0.05). In conclusion, the results of present study indicated that vegetable oils such as CO, RO and LO can potentially be used as dietary FO substitutes for juvenile largemouth bass.

Decabromodiphenyl ether-induced PRKACA hypermethylation contributed to glycolipid metabolism disorder via regulating PKA/AMPK pathway in rat and L-02 cells

BDE-209 is the most prevalent congener of polybrominated diphenyl ethers and has high bioaccumulation in humans and animals. BDE-209 has been reported to disrupt glycolipid metabolism, but the mechanisms are still unclear. In this study, we found that BDE-209 induced liver tissue injury and hepatotoxicity, increased the glucose and total cholesterol levels in the serum of rats, and increased glucose and triglyceride levels in L-02 cells. BDE-209 exposure changed the PKA, p-PKA, AMPK, p-AMPK, ACC, and FAS expression in rats’ liver and L-02 cells. Moreover, BDE-209 induced PRKACA-1 hypermethylation in L-02 cells. AMPK activator (AICAR) inhibited the changes of p-AMPK, ACC, and FAS expression and elevation of glucose and triglyceride levels induced by BDE-209. DNA methylation inhibitor (5-Aza-CdR) reversed BDE-209 induced alters of PKA/AMPK/ACC/FAS signaling pathway. These results demonstrated that BDE-209 could disrupt the glycolipid metabolism by causing PRKACA-1 hypermethylation to regulate the PKA/AMPK signaling pathway in hepatocytes.

FADS1 overexpression promotes fatty acid synthesis and triacylglycerol accumulation via inhibiting the AMPK/SREBP1 pathway in goat mammary epithelial cells.

Delta-5 desaturase (D5D), encoded by the fatty acid desaturase 1 (FADS1) gene, is a rate-limiting enzyme in polyunsaturated fatty acid (PUFA) synthesis that influences the PUFA levels in milk fat. However, the function and molecular mechanism of FADS1 in milk fat metabolism remain largely unknown. The FADS1 overexpression increased the triglyceride content, lipid droplet size, and expression of genes related to fatty acid de novo synthesis (SREBP1 and ACC), intracellular fatty acid transporters (FABP3 and FABP4) and triacylglycerol synthesis gene (DGAT2). It also significantly promoted the SREBP1 nuclear translocation by inhibiting the AMPK activation. In addition, FADS1 overexpression inhibited cell proliferation and arrested cell cycle at the G1 phase. These findings reveal a novel FADS1-AMPK-SREBP1 pathway regulating milk fat production in the goat mammary gland.

Expression of Membrane Bound O-Acyltransferase Domain Containing 7 after Myocardial Infarction and its Role in Lipid Metabolism in vitro.

Background: Previous microarray analysis on peripheral blood leukocytes from three patients with acute myocardial infarction (AMI) showed that elevated expression of membrane bound o-acyltransferase domain containing 7(MBOAT7) relative to control. To further verify these findings, we investigated more patients and explored the possible mechanisms in vitro.Objective: To study alterations in MBOAT7 expression in leukocytes after AMI, and to explore the relationship between MBOAT7 and lipid metabolism pathways in hepatocytes in vitro.Methods: Ninety patients with AMI and 90 controls were recruited from the Han population in Northeast China. RT-fluorescent PCR was used to measure MBOAT7 mRNA levels. MBOAT7 interference and overexpression vectors were constructed and transfected into L-02 hepatocytes and expression was examined by RT-qPCR and western blotting. The expression of SCAP, LDLR, HMGCR, ACAT1, ABCA1, SREBP1, ACC, FAS, SCD, and PPARγ in the lipid metabolism pathway were investigated by RT-qPCR. Triglyceride and cholesterol levels were measured by ELISA.Results: It was found that MBOAT7 mRNA levels were elevated in the leukocytes of patients with AMI. Hepatocytes were successfully transfected, shown by attenuated MBOAT7 mRNA levels in the silenced group (0.41±0.04 vs 1.01±0.07 for control, P=0.0019 <0.01) and raised levels in the overexpressing cells (23.29±0.39 vs 1.00±0.06 for control, P <0.0001). These results were confirmed by western blotting. Expression of the lipid metabolism-related genes was altered in response to MBOAT7 expression. Triglyceride levels increased after MBOAT7 silencing (118.40 ± 2.26 vs 70.54 ± 0.25 for control, P<0.0001), as did those of cholesterol (628.30 ± 8.89 vs 544.70 ± 11.04, P = 0.0041) but were not altered on MBOAT7 overexpression.Conclusion: MBOAT7 did not affect the metabolism of triglycerides in hepatocytes through fatty acid synthesis and decomposition pathways. The MBOAT7 level in the peripheral blood can be used as a marker for acute myocardial infarction but cannot be used as a single therapeutic target to regulate lipid metabolism.