SREBP-1c overexpression induces triglycerides accumulation through increasing lipid synthesis and decreasing lipid oxidation and VLDL assembly in bovine hepatocytes.

Published on Sep 1, 2014in The Journal of Steroid Biochemistry and Molecular Biology3.813
· DOI :10.1016/J.JSBMB.2014.02.009
Yu Li11
Estimated H-index: 11
(JLU: Jilin University)
Abstract The natural incidence of fatty liver in ruminants is significantly higher than in monogastric animals. Fatty liver is associated with sterol regulatory element-binding protein 1c (SREBP-1c). The aim of this study was to investigate the regulatory network effects of SREBP-1c on the lipid metabolic genes involved in fatty acid uptake, activation, oxidation, synthesis, and very low-density lipoprotein (VLDL) assembly in bovine hepatocytes. In vitro , bovine hepatocytes were transfected with an adenovirus-mediated SREBP-1c overexpression vector. SREBP-1c overexpression significantly up-regulated the expression and activity of the fatty acid uptake, activation, and synthesis enzymes: liver fatty acid binding protein, fatty acid translocase, acyl-CoA synthetase long-chain 1, acetyl-CoA carboxylase 1, and fatty acid synthase, increasing triglyceride (TG) synthesis and accumulation. SREBP-1c overexpression down-regulated the expression and activity of the lipid oxidation enzymes: carnitine palmitoyltransferase 1 and carnitine palmitoyltransferase 2. Furthermore, the apolipoprotein B100 expression and microsomal triglyceride transfer protein activity were significantly decreased. SREBP-1c overexpression reduced lipid oxidation and VLDL synthesis, thereby decreasing TG disposal and export. Therefore, large amounts of TG accumulated in the bovine hepatocytes. Taken together, these results indicate that SREBP-1c overexpression increases lipid synthesis and decreases lipid oxidation and VLDL export, thereby inducing TG accumulation in bovine hepatocytes.
📖 Papers frequently viewed together
541 Citations
57 Citations
64 Citations
#3Yu Li (JLU: Jilin University)H-Index: 11
Abstract High serum concentrations of nonesterified fatty acids (NEFA), which may affect the synthesis and assembly of very low density lipoproteins (VLDL), are associated with fatty liver during the early lactation period. Therefore, the objective of this study was to investigate the effects of NEFA on the synthesis and assembly of VLDL in bovine hepatocytes. Bovine hepatocytes were cultured and treated with different concentrations of NEFA. The mRNA expression of apolipoprotein B100 ( ApoB100 ...
28 CitationsSource
#1Yi-Ming Su (Fujian Medical University)H-Index: 2
#2Guorong Lv (Fujian Medical University)H-Index: 7
Last. Huitong Lin (Fujian Medical University)H-Index: 2
view all 5 authors...
Exposure to an adverse intrauterine environment increases the risk for adult metabolic syndrome. However, the influence of prenatal hypoxia on the risk of fatty liver disease in offspring is unclear. The purpose of the present study was to evaluate the role of reduced fetal oxygen on the development and severity of high-fat (HF) diet-induced nonalcoholic fatty liver disease (NAFLD). Based on design implicating 2 factors, ie, maternal hypoxia (MH) and postnatal HF diet, blood lipid and insulin le...
10 CitationsSource
#1Xinwei Li (JLU: Jilin University)H-Index: 23
#2Hui Chen (JLU: Jilin University)H-Index: 93
Last. Zhe Wang (JLU: Jilin University)H-Index: 26
view all 9 authors...
The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK) signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic ...
53 CitationsSource
#1Xinwei Li (JLU: Jilin University)H-Index: 23
#2Xiaobing Li (JLU: Jilin University)H-Index: 22
Last. Zhe Wang (JLU: Jilin University)H-Index: 26
view all 14 authors...
Non-esterified fatty acids (NEFAs) act as signaling molecules involved in regulating genes expression to modulate lipid metabolism. However, the regulation mechanism of NEFAs on lipid metabolism in dairy cows is unclear. The AMP-activated protein kinase (AMPK) signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of NEFAs and AMPKα inhibitors (BML-275). NEFAs increased AMPKα phosphorylation ...
23 CitationsSource
#1Xuguang Zhai (Nantong University)H-Index: 9
#2Kunfeng Yan (Nantong University)H-Index: 3
Last. Yajun Zhou (Nantong University)H-Index: 11
view all 8 authors...
Background and Purpose Liver fibrosis is commonly associated with obesity and most obese patients develop hyperleptinaemia. The adipocytokine leptin has a unique role in the development of liver fibrosis. Activation of hepatic stellate cells (HSCs) is a key step in hepatic fibrogenesis and sterol regulatory element-binding protein-1c (SREBP-1c) can inhibit HSC activation. We have shown that leptin strongly inhibits SREBP-1c expression in rat HSCs. Hence, we aimed to clarify whether the β-catenin...
47 CitationsSource
#1Yuhui WangH-Index: 1
#2Hei Sook Sul (University of California, Berkeley)H-Index: 57
are tightly and coordinately regulated, including enzymes in FA synthesis, such as ACL, ACC, FAS and stearoyl-CoA desaturase, enzymes in the production of NADPH required for FAS activity, such as malic enzyme and glucose-6-phosphate dehydrogenase, as well as enzymes in esterification for TAG synthesis, such as mGPAT and diacylglycerol acyltransferase. Some glycolytic enzymes, such as glucokinase and liver pyruvate kinase, are also regulated in a similar fashion to lipogenic enzymes to provide th...
2 CitationsSource
#1William J. Quinn (UPenn: University of Pennsylvania)H-Index: 20
#2Morris J. Birnbaum (UPenn: University of Pennsylvania)H-Index: 110
In recent years, it has become increasingly apparent that common polygenic diseases generally do not result from accumulated defects in a single pathway but, rather, present as complex interactions among multiple environmental and inherited factors. Nowhere is this more obvious than in diabetes mellitus, which is classified into at least two groups, type 1 and type 2 (T2DM), that share hyperglycemia but differ in the initiating primary immune destruction of the β-cells or insulin resistance, res...
21 CitationsSource
#1Linkang Zhou (THU: Tsinghua University)H-Index: 17
#2Li XuH-Index: 77
Last. Peng Li (THU: Tsinghua University)H-Index: 86
view all 10 authors...
High levels of dietary saturated fat have been closely associated with the development of hepatic steatosis, but the factors that mediate this process remain elusive. Here, we observed that the level of cell death-inducing DNA fragmentation factor-alpha-like effector a (Cidea) expression was highly correlated with the severity of hepatic steatosis in humans. Overexpression of Cidea in mouse liver resulted in increased hepatic lipid accumulation and the formation of large lipid droplets (LDs). In...
119 CitationsSource
#1Xinwei Li (JLU: Jilin University)H-Index: 23
#2Xiaobing Li (JLU: Jilin University)H-Index: 22
Last. Zhe Wang (JLU: Jilin University)H-Index: 26
view all 9 authors...
Dairy cows experience an increased demand for glucose to support milk production. However, negative energy balance is a common condition in peripartum cows. In response, fat mobilization provides non-esterified fatty acids (NEFAs) for oxidation in the liver to generate ATP. To investigate the effects of NEFAs on gluconeogenesis, the expression and enzyme activity of pyruvate carboxylase (PC) and phosphoenolpyruvate carboxylase (PEPCK) in cultured bovine hepatocytes were evaluated by quantitative...
24 CitationsSource
#1Yu Li (BU: Boston University)H-Index: 20
#2Shanqin Xu (BU: Boston University)H-Index: 22
Last. Mengwei Zang (BU: Boston University)H-Index: 27
view all 16 authors...
Summary AMPK has emerged as a critical mechanism for salutary effects of polyphenols on lipid metabolic disorders in type 1 and type 2 diabetes. Here we demonstrate that AMPK interacts with and directly phosphorylates sterol regulatory element binding proteins (SREBP-1c and -2). Ser372 phosphorylation of SREBP-1c by AMPK is necessary for inhibition of proteolytic processing and transcriptional activity of SREBP-1c in response to polyphenols and metformin. AMPK stimulates Ser372 phosphorylation, ...
1,001 CitationsSource
Cited By59
#1Fengcui Sun (SDUTCM: Shandong University of Traditional Chinese Medicine)H-Index: 1
#2Xiufen Yang (SDUTCM: Shandong University of Traditional Chinese Medicine)H-Index: 1
Last. Fengxia Zhang (SDUTCM: Shandong University of Traditional Chinese Medicine)H-Index: 2
view all 10 authors...
Hyperlipidemia is a disorder of lipid metabolism, which is a major cause of coronary heart disease. Although there has been considerable progress in hyperlipidemia treatment, morbidity and risk associated with the condition continue to rise. The first-line treatment for hyperlipidemia, statins, has multiple side effects; therefore, development of safe and effective drugs from natural products to prevent and treat hyperlipidemia is necessary. Diosgenin is primarily derived from fenugreek (Trigone...
#1Xin Ren (BTBU: Beijing Technology and Business University)H-Index: 1
#2Linxuan Wang (BTBU: Beijing Technology and Business University)
Last. Qun Shen (CAU: China Agricultural University)H-Index: 16
view all 7 authors...
Foxtail millet (FM) is receiving ongoing increased attention due to its beneficial health effects, including the hypoglycemic effect. However, the underlying mechanisms of the hypoglycemic effect have been underexplored. In the present study, the hypoglycemic effect of FM supplementation was confirmed again in high-fat diet and streptozotocin-induced diabetic rats with significantly decreased fasting glucose (FG), glycated serum protein, and areas under the glucose tolerance test (p < 0.05). We ...
#1Angel P. Y. Ma (Li Ka Shing Faculty of Medicine, University of Hong Kong)
#2Cherlie L. S. Yeung (Li Ka Shing Faculty of Medicine, University of Hong Kong)
Last. Judy Wai Ping Yam (HKU: University of Hong Kong)H-Index: 21
view all 13 authors...
Lipid accumulation exacerbates tumor development, as it fuels the proliferative growth of cancer cells. The role of medium-chain acyl-CoA dehydrogenase (ACADM), an enzyme that catalyses the first step of mitochondrial fatty acid oxidation, in tumor biology remains elusive. Therefore, investigating its mode of dysregulation can shed light on metabolic dependencies in cancer development. In hepatocellular carcinoma (HCC), ACADM was significantly underexpressed, correlating with several aggressive ...
1 CitationsSource
#1Yan Huang (NWAFU: Northwest A&F University)H-Index: 2
#2Chenxu Zhao (NWAFU: Northwest A&F University)H-Index: 1
Last. Jianguo Wang (NWAFU: Northwest A&F University)H-Index: 10
view all 10 authors...
Abstract During the periparturient transition period, negative energy balance (NEB) characterized by high concentrations of non-esterified fatty acids (NEFA) may cause fatty liver and ketosis in dairy cows. Previous studies have shown that the protein kinase R-like endoplasmic reticulum kinase (PERK) branch of the endoplasmic reticulum stress (ERS) response plays an important role in lipid metabolism in hepatocytes. This study, therefore, investigated the role of the PERK-branch in NEFA-induced ...
1 CitationsSource
#1Massimo Bionaz (OSU: Oregon State University)H-Index: 34
#2Einar Vargas-Bello-Pérez (UCPH: University of Copenhagen)H-Index: 10
Last. Sebastiano Busato (OSU: Oregon State University)H-Index: 4
view all 3 authors...
High producing dairy cows generally receive in the diet up to 5-6% of fat. This is a relatively low amount of fat in the diet compared to diets in monogastrics; however, dietary fat is important for dairy cows as demonstrated by the benefits of supplementing cows with various fatty acids (FA). Several FA are highly bioactive, especially by affecting the transcriptome; thus, they have nutrigenomic effects. In the present review, we provide an up-to-date understanding of the utilization of FA by d...
8 CitationsSource
ABSTRACT Dairy cows with fatty liver exhibit hepatic lipid accumulation and disturbances in fatty acid oxidation and lipid transport. Phosphatase and tensin homolog (PTEN), a lipid phosphatase, regulates intrahepatic fatty acid oxidation and lipid transport in mice. Whether PTEN play a role in fatty acid oxidation and very low density lipoprotein (VLDL) assembly in calf hepatocytes are unknown. Hepatocytes isolated from 3 healthy female Holstein calves (1 d old, 30–40 kg) were infected with empt...
1 CitationsSource
#1Velid UnsalH-Index: 6
#2Köksal DeveciH-Index: 1
Last. Mehmet Kemal TumerH-Index: 3
view all 4 authors...
The debate on the metabolic effects of high fructose corn syrup (HFCS) continues. The deterioration of endoplasmic reticulum (ER) homeostasis is called ER stress. Glucose-regulated protein-78 (GRP-78) and X-box binding protein-1 (XBP-1) are key markers of ER stress and the therapeutic targets of diseases. Sterol regulatory element binding protein-1c (SREBP-1c) is the most important transcription factor that regulates the expression of enzymes for fatty acid synthesis. The purpose of this paper i...
1 CitationsSource
#1Kairui Tang (JNU: Jinan University)H-Index: 4
#2Yuanjun Deng (JNU: Jinan University)H-Index: 7
Last. Yupei Zhang (JNU: Jinan University)H-Index: 6
view all 9 authors...
Background. Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide, and its incidence is increasing annually, but there is currently no specific drug for treating NAFLD. Shenling Baizhu powder (SL) is a safe herbal compound commonly used in clinical practice. Our previous research has shown that SL has the effect of preventing NAFLD, but its specific mechanism has not been determined. In this study, the potential mechanism of SL on NAFLD was explored by in vivo expe...
#1Zhen Chen (Hokkaido University)H-Index: 75
#2Yue Wu (Hokkaido University)H-Index: 5
Last. Shu-Ping Hui (Hokkaido University)H-Index: 21
view all 8 authors...
Abstract A comparative lipidomic profiling analysis of dairy cattle oocytes with different developmental competences was performed using a combination of high performance liquid chromatography-high resolution tandem mass spectrometry and multivariate statistical analysis. Significant lipidomic changes were identified in degenerating oocytes. Total triacylglycerol in the degenerating oocytes was 1.8-fold higher than that in the normal oocytes; however, total cardiolipin was 53.5% lesser than that...
4 CitationsSource
#1Jihong Dong (JLU: Jilin University)H-Index: 7
#2Juan J. Loor (UIUC: University of Illinois at Urbana–Champaign)H-Index: 68
Last. Xinwei Li (JLU: Jilin University)H-Index: 23
view all 13 authors...
ABSTRACT High blood concentrations of nonesterified fatty acids (NEFA) and altered lipid metabolism are key characteristics of fatty liver in dairy cows. In nonruminants, the mitochondrial membrane protein mitofusin 2 (MFN2) plays important roles in regulating mitochondrial function and intrahepatic lipid metabolism. Whether MFN2 is associated with hepatic lipid metabolism in dairy cows with moderate fatty liver is unknown. Therefore, to investigate changes in MFN2 expression and lipid metabolic...
6 CitationsSource