scholarly journals Caffeine and EGCG Alleviate High-Trans Fatty Acid and High-Carbohydrate Diet-Induced NASH in Mice: Commonality and Specificity

2021 ◽  
Vol 8 ◽  
Author(s):  
Xin Xin ◽  
Chen Cheng ◽  
Cai Bei-yu ◽  
Li Hong-shan ◽  
Tian Hua-jie ◽  
...  

Caffeine and epigallocatechin-3-gallate (EGCG), which respectively, are the main functional extracts from coffee and green tea, and present protective effects against non-alcoholic fatty liver diseases (NAFLD). These two beverages and their functional extracts are highly recommended as potential treatments for obesity and NAFLD in clinics; however, their pharmacodynamic effects and pharmacological mechanisms in non-alcoholic steatohepatitis (NASH) remain unclear. Therefore, the aim of this study was to explore the commonality and specificity of the pharmacodynamic effects and pharmacological mechanisms of caffeine and EGCG on NASH mice, which were fed with a high-trans fatty acid/high-carbohydrate (HFHC) diet. C57BL/6J mice were fed a normal diet (control group) or an HFHC diet (HFHC group) for 24 weeks. HFHC group mice were additionally treated with caffeine (75 mg/kg) or EGCG (100 mg/kg) for 6 weeks, using obeticholic acid (OCA,10 mg/kg) as a positive control group. The pharmacological effects of the drugs, including effects on glucose and lipid metabolism and liver inflammation and fibrosis, were evaluated. Gene expression in liver tissue samples from the different groups were assessed. Both caffeine and EGCG significantly reduced the liver manifestations of NASH induced by HFHC. The pathological aspects of liver lipid deposition, inflammation, and liver fibrosis in both groups were strongly ameliorated. Of note, most indexes were strongly reversed in the caffeine group, although AST activity, fasting blood glucose, and the HOMA-IR index were improved in the ECGC group. There were 714 differentially expressed genes between the caffeine and HFHC groups and 268 differentially expressed genes between the EGCG and HFHC groups. Twenty and 17 NASH-related KEGG signaling pathways were enriched by caffeine and EGCG. This study confirmed that 75 mg/kg caffeine and 100 mg/kg EGCG could significantly improve liver lipid deposition, glucose metabolism, inflammation, and fibrosis in a mouse model of NASH induced by HFHC. The bioinformatics platform we built for caffeine and EGCG in NASH disease found that the two drugs may greatly overlap in improving the mechanism related to NASH inflammation. However, caffeine may have better potential in regulating glucose metabolism and EGCG may have better potential in regulating lipid metabolism.

2020 ◽  
pp. 1-10
Author(s):  
Renlei Ji ◽  
Xiaojun Xiang ◽  
Xueshan Li ◽  
Kangsen Mai ◽  
Qinghui Ai

Abstract A 10-week feeding trial was conducted to investigate the effect of dietary curcumin (CC) on growth antioxidant responses, fatty acid composition, and expression of lipid metabolism-related genes of large yellow croaker fed a high-fat diet (HFD). Four diets (lipid level at 18 %) were formulated with different levels of curcumin (0, 0·02, 0·04 and 0·06 %). The best growth performance was found in the 0·04 % curcumin group, with the body and hepatic lipid levels lower than the control group (0 % CC). The content of TAG, total cholesterol and LDL-cholesterol was the least in the 0·06 % curcumin group. The lowest malondialdehyde and the highest superoxide dismutase, catalase and total antioxidant capacity were observed in the 0·04 % curcumin group. The 0·04 % curcumin group had higher expression of Δ6fad, elovl5 and elovl4 and showed higher hepatic n-6 and n-3 PUFA. Expression of ppara, cpt1, and aco was significantly increased, while expression of srebp1 and fas was dramatically decreased in curcumin groups compared with the control group. Overall, 0·04 % curcumin supplementation could mitigate the negative effects caused by HFD and promote growth via reducing hepatic lipid deposition, improving antioxidant activity and increasing PUFA of large yellow croaker. To conclude, abnormal hepatic lipid deposition was probably due to increased fatty acid oxidation and reduced de novo synthesis of fatty acids.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zheng Ma ◽  
Na Luo ◽  
Lu Liu ◽  
Huanxian Cui ◽  
Jing Li ◽  
...  

Abstract Background A body distribution with high intramuscular fat and low abdominal fat is the ideal goal for broiler breeding. Preadipocytes with different origins have differences in terms of metabolism and gene expression. The transcriptome analysis performed in this study of intramuscular preadipocytes (DIMFPs) and adipose tissue-derived preadipocytes (DAFPs) aimed to explore the characteristics of lipid deposition in different chicken preadipocytes by dedifferentiation in vitro. Results Compared with DAFPs, the total lipid content in DIMFPs was reduced (P < 0.05). Moreover, 72 DEGs related to lipid metabolism were screened, which were involved in adipocyte differentiation, fatty acid transport and fatty acid synthesis, lipid stabilization, and lipolysis. Among the 72 DEGs, 19 DEGs were enriched in the PPAR signaling pathway, indicating its main contribution to the regulation of the difference in lipid deposition between DAFPs and DIMFPs. Among these 19 genes, the representative APOA1, ADIPOQ, FABP3, FABP4, FABP7, HMGCS2, LPL and RXRG genes were downregulated, but the ACSL1, FABP5, PCK2, PDPK1, PPARG, SCD, SCD5, and SLC27A6 genes were upregulated (P < 0.05 or P < 0.01) in the DIMFPs. In addition, the well-known pathways affecting lipid metabolism (MAPK, TGF-beta and calcium) and the pathways related to cell communication were enriched, which may also contribute to the regulation of lipid deposition. Finally, the regulatory network for the difference in lipid deposition between chicken DAFPs and DIMFPs was proposed based on the above information. Conclusions Our data suggested a difference in lipid deposition between DIMFPs and DAFPs of chickens in vitro and proposed a molecular regulatory network for the difference in lipid deposition between chicken DAFPs and DIMFPs. The lipid content was significantly increased in DAFPs by the direct mediation of PPAR signaling pathways. These findings provide new insights into the regulation of tissue-specific fat deposition and the optimization of body fat distribution in broilers.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9673
Author(s):  
Jingan Wang ◽  
Kaijun Zhang ◽  
Xin Hou ◽  
Wucheng Yue ◽  
He Yang ◽  
...  

Activin receptor IIB (ActRIIB) is a serine/threonine-kinase receptor binding with transforming growth factor-β (TGF-β) superfamily ligands to participate in the regulation of muscle mass in vertebrates. However, its structure and function in crustaceans remain unknown. In this study, the ActRIIB gene in Eriocheir sinensis (Es-ActRIIB) was cloned and obtained with a 1,683 bp open reading frame, which contains the characteristic domains of TGF-β type II receptor superfamily, encoding 560 amino acids. The mRNA expression of Es-ActRIIB was the highest in hepatopancreas and the lowest in muscle at each molting stage. After injection of Es-ActRIIB double-stranded RNA during one molting cycle, the RNA interference (RNAi) group showed higher weight gain rate, higher specific growth rate, and lower hepatopancreas index compared with the control group. Meanwhile, the RNAi group displayed a significantly increased content of hydrolytic amino acid in both hepatopancreas and muscle. The RNAi group also displayed slightly higher contents of saturated fatty acid and monounsaturated fatty acid but significantly decreased levels of polyunsaturated fatty acid compared with the control group. After RNAi on Es-ActRIIB, the mRNA expressions of five ActRIIB signaling pathway genes showed that ActRI and forkhead box O (FoxO) were downregulated in hepatopancreas and muscle, but no significant expression differences were found in small mother against decapentaplegic (SMAD) 3, SMAD4 and mammalian target of rapamycin. The mRNA expression s of three lipid metabolism-related genes (carnitine palmitoyltransferase 1β (CPT1β), fatty acid synthase, and fatty acid elongation) were significantly downregulated in both hepatopancreas and muscle with the exception of CPT1β in muscles. These results indicate that ActRIIB is a functionally conservative negative regulator in growth mass, and protein and lipid metabolism could be affected by inhibiting ActRIIB signaling in crustacean.


2010 ◽  
Vol 140 (5) ◽  
pp. 919-924 ◽  
Author(s):  
Anil K. G. Kadegowda ◽  
Erin E. Connor ◽  
Beverly B. Teter ◽  
Joseph Sampugna ◽  
Pierluigi Delmonte ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kai Xing ◽  
Xitong Zhao ◽  
Hong Ao ◽  
Shaokang Chen ◽  
Ting Yang ◽  
...  

AbstractFat deposition is very important in pig production, and its mechanism is not clearly understood. MicroRNAs (miRNAs) play critical roles in fat deposition and energy metabolism. In the current study, we investigated the mRNA and miRNA transcriptome in the livers of Landrace pigs with extreme backfat thickness to explore miRNA-mRNA regulatory networks related to lipid deposition and metabolism. A comparative analysis of liver mRNA and miRNA transcriptomes from pigs (four pigs per group) with extreme backfat thickness was performed. We identified differentially expressed genes from RNA-seq data using a Cufflinks pipeline. Seventy-one differentially expressed genes (DEGs), including twenty-eight well annotated on the porcine reference genome genes, were found. The upregulation genes in pigs with higher backfat thickness were mainly involved in fatty acid synthesis, and included fatty acid synthase (FASN), glucokinase (GCK), phosphoglycerate dehydrogenase (PHGDH), and apolipoprotein A4 (APOA4). Cytochrome P450, family 2, subfamily J, polypeptide 34 (CYP2J34) was lower expressed in pigs with high backfat thickness, and is involved in the oxidation of arachidonic acid. Moreover, 13 differentially expressed miRNAs were identified. Seven miRNAs were associated with fatty acid synthesis, lipid metabolism, and adipogenic differentiation. Based on comprehensive analysis of the transcriptome of both mRNAs and miRNAs, an important regulatory network, in which six DEGs could be regulated by differentially expressed miRNAs, was established for fat deposition. The negative correlate in the regulatory network including, miR-545-5p and GRAMD3, miR-338 and FASN, and miR-127, miR-146b, miR-34c, miR-144 and THBS1 indicate that direct suppressive regulation may be involved in lipid deposition and energy metabolism. Based on liver mRNA and miRNA transcriptomes from pigs with extreme backfat thickness, we identified 28 differentially expressed genes and 13 differentially expressed miRNAs, and established an important miRNA-mRNA regulatory network. This study provides new insights into the molecular mechanisms that determine fat deposition in pigs.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Meng Zhang ◽  
Fang Li ◽  
Xiang-fei Ma ◽  
Wen-ting Li ◽  
Rui-rui Jiang ◽  
...  

Abstract Background The distribution and deposition of fat tissue in different parts of the body are the key factors affecting the carcass quality and meat flavour of chickens. Intramuscular fat (IMF) content is an important factor associated with meat quality, while abdominal fat (AbF) is regarded as one of the main factors affecting poultry slaughter efficiency. To investigate the differentially expressed genes (DEGs) and molecular regulatory mechanisms related to adipogenic differentiation between IMF- and AbF-derived preadipocytes, we analysed the mRNA expression profiles in preadipocytes (0d, Pre-) and adipocytes (10d, Ad-) from IMF and AbF of Gushi chickens. Results AbF-derived preadipocytes exhibited a higher adipogenic differentiation ability (96.4% + 0.6) than IMF-derived preadipocytes (86.0% + 0.4) (p < 0.01). By Ribo-Zero RNA sequencing, we obtained 4403 (2055 upregulated and 2348 downregulated) and 4693 (2797 upregulated and 1896 downregulated) DEGs between preadipocytes and adipocytes in the IMF and Ad groups, respectively. For IMF-derived preadipocyte differentiation, pathways related to the PPAR signalling pathway, ECM-receptor interaction and focal adhesion pathway were significantly enriched. For AbF-derived preadipocyte differentiation, the steroid biosynthesis pathways, calcium signaling pathway and ECM-receptor interaction pathway were significantly enriched. A large number of DEGs related to lipid metabolism, fatty acid metabolism and preadipocyte differentiation, such as PPARG, ACSBG2, FABP4, FASN, APOA1 and INSIG1, were identified in our study. Conclusion This study revealed large transcriptomic differences between IMF- and AbF-derived preadipocyte differentiation. A large number of DEGs and transcription factors that were closely related to fatty acid metabolism, lipid metabolism and preadipocyte differentiation were identified in the present study. Additionally, the microenvironment of IMF- and AbF-derived preadipocyte may play a significant role in adipogenic differentiation. This study provides valuable evidence to understand the molecular mechanisms underlying adipogenesis and fat deposition in chickens.


2017 ◽  
Vol 312 (1) ◽  
pp. E11-E18 ◽  
Author(s):  
Anantha Metlakunta ◽  
Wan Huang ◽  
Maja Stefanovic-Racic ◽  
Nikolaos Dedousis ◽  
Ian Sipula ◽  
...  

Leptin has potent effects on lipid metabolism in a number of peripheral tissues. In liver, an acute leptin infusion (~120 min) stimulates hepatic fatty acid oxidation (~30%) and reduces triglycerides (TG, ~40%), effects that are dependent on phosphoinositol-3-kinase (PI3K) activity. In the current study we addressed the hypothesis that leptin actions on liver-resident immune cells are required for these metabolic effects. Myeloid cell-specific deletion of the leptin receptor (ObR) in mice or depletion of liver Kupffer cells (KC) in rats in vivo prevented the acute effects of leptin on liver lipid metabolism, while the metabolic effects of leptin were maintained in mice lacking ObR in hepatocytes. Notably, liver TG were elevated in both lean and obese myeloid cell ObR, but the degree of obesity and insulin resistance induced by a high-fat diet was similar to control mice. In isolated primary hepatocytes (HEP), leptin had no effects on HEP lipid metabolism and only weakly stimulated PI3K. However, the coculture of KC with HEP restored leptin action on HEP fatty acid metabolism and stimulation of HEP PI3K. Notably, leptin stimulated the release from KC of a number of cytokines. However, the exposure of HEP to these cytokines individually [granulocyte macrophage colony-stimulating factor, IL-1α, IL-1β, IL-6, IL-10, and IL-18] or in combination had no effects on HEP lipid metabolism. Together, these data demonstrate a role for liver mononuclear cells in the regulation of liver lipid metabolism by leptin.


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Zengpeng Lv ◽  
Hao Fan ◽  
Bochen Song ◽  
Guang Li ◽  
Dan Liu ◽  
...  

The experiment was designed to clarify the effect and molecular mechanism of maternal genistein (GEN) on the lipid metabolism and developmental growth of offspring chicks. Laying broiler breeder (LBB) hens were supplemented with 40 mg/kg genistein (GEN), while the control group was fed with the low-soybean meal diet. The offspring chicks were grouped according to the mother generation with 8 replicates each. Hepatic transcriptome data revealed 3915 differentially expressed genes (DEGs, P adjusted < 0.05, fold change>1.5 or fold change<0.67) between chicks in the two groups. Maternal GEN activated the GH-IGF1-PI3K/Akt signaling pathway, which promoted the developmental processes and cellular amino acid metabolic processes, as well as inhibited the apoptotic process. GEN treatment significantly increased the weight gain, breast muscle percentage, and liver index in chicks. PANTHER clustering analysis suggested that maternal GEN enhanced the antioxidant activity of chicks by the upregulation of gene (SOD3, MT1, and MT4) expression. Accordingly, the activities of T-AOC and T-SOD in the liver were increased after GEN treatment. The overrepresentation tests revealed that maternal GEN influenced the glycolysis, unsaturated fatty acid biosynthesis, acyl-coenzyme A metabolism, lipid transport, and cholesterol metabolism in the chick livers. Hepatic cholesterol and long-chain fatty acid were significantly decreased after GEN treatment. However, the level of arachidonic acid was higher in the livers of the GEN-treated group compared with the CON group. Moreover, GEN treatment enhanced fatty acid β-oxidation and upregulated PPARδ expression in the chick liver. ChIP-qPCR analysis indicated that maternal GEN might induce histone H3-K36 trimethylation in the promoter region of PPARδ gene (PPARD) through Iws1, methyltransferases. It also induced histone H4-K12 acetylation at the PPARD promoter through MYST2, which activated the PPAR signaling pathways in the chick livers. In summary, supplementing LBB hens with GEN can alter lipid metabolism in the offspring chicks through epigenetic modification and improve the antioxidative capability as well as growth performance.


2020 ◽  
Vol 11 ◽  
Author(s):  
Junpeng Yao ◽  
Pengcheng Hu ◽  
Yanhong Zhu ◽  
Yingyan Xu ◽  
Qingsong Tan ◽  
...  

Compared with wild grass carp (Ctenopharyngodon idellus), intensively cultured fish displayed disordered lipid metabolism, showing excess lipid deposition in the hepatopancreas and muscle. Lotus leaf prevents fat accumulation in humans and may have similar effects on fish. This study explored the regulatory mechanisms by which the dietary addition of an alcoholic extract of lotus leaf (AELL) reduced lipid deposition in the hepatopancreas and muscle of juvenile grass carp. The fish (average initial weight: 34.00 ± 0.40 g) were fed four experimental diets containing different AELL levels (0, 0.07, 0.14, and 0.21%) for 8 weeks. Serum components, lipid droplet size, triacylglycerol (TAG) content, enzymatic activities, and mRNA levels of genes related to lipid metabolism in the hepatopancreas and muscle were analyzed. The results show that dietary AELL supplementation significantly reduced the TAG content and lipid droplet area in the histological sections as well as the fatty acid synthase (FAS) activity in both the hepatopancreas and muscle but enhanced the activities of lipoprotein lipase (LPL) and carnitine palmitoyltransferase I (CPT1) in both tissues. In addition, dietary AELL supplementation decreased the mRNA expression of genes involved in fatty acid uptake (cd36, fatp1/fatp4/fatp6, fabp10/fabp11, acsl1/acsl4) and de novo lipid synthesis (pgd, g6pd, and fasn) as well as the transcription factors pparg and srebf1 in the hepatopancreas and muscle but increased the mRNA levels of genes relating to lipid catabolism (cpt1a, lipe, pnpla2, lpl), lipid transportation (apob), and the transcription factor ppara in both tissues. In conclusion, dietary AELL supplementation reduced lipid accumulation in the hepatopancreas and muscle by affecting the gene expression of proteins with known effects on lipid metabolism in juvenile grass carp.


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