Increase of fatty acid oxidation and VLDL assembly and secretion overexpression of PTEN in cultured hepatocytes of newborn calf.

Published on Jan 1, 2012in Cellular Physiology and Biochemistry
· DOI :10.1159/000341477
Shixin Fu5
Estimated H-index: 5
 , Qinghua Deng9
Estimated H-index: 9
 + 7 AuthorsGuowen Liu27
Estimated H-index: 27
Source
Abstract
Background: Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene that also plays a vital role in regulating fatty acid metabolism. Here we attempted to elucidate the role of PTEN in the regulation of fatty acid oxidation and the assembly and secretion of very low density lipoprotein (VLDL) in dairy cow liver. Methods: We transfected primary culture calf hepatocytes with adenovirus-mediated PTEN overexpression vector (AD-GFP-PTEN).PTEN-overexpressing hepatocytes and control hepatocytes were obtained. Results: Compared with controls, overexpression of PTEN significantly up-regulated CPT I, ACSL, HADH expression (ppl0.01), ApoE (ppppagt;0.05). To demonstrate that fatty acid metabolism was changed, we measured the concentrations of TG and VLDL. The concentration of TG was significantly decreased in hepatocytes (pPConclusions: Overexpressing PTEN enhanced fatty acid oxidation and assembly and secretion of VLDL. PTEN gene therapy could have therapeutic potential for fatty liver diseases of dairy cattle.
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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...
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Nov 11, 2011·Lipids in Health and Disease3.88
#1Fu-Bing Wang (WHU: Wuhan University)H-Index: 22
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Background: Liver dominates the production and secretion of apolipoprotein B (apoB) and evidence shows that liver malfunction induced by hepatitis B virus (HBV) infection could lead to apolipoprotein metabolism disorders. The present study was undertaken to assess the effects of HBV on apoB expression. Methods: Clinical examination: serum apoB levels in patients with chronic HBV infection and in healthy individuals were measured by immunoturbidimetry using biochemical analyzer Olympus 5400. Cell...
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Jul 22, 2011·Journal of Biological Chemistry5.16
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#3Charles L. Hoppel (Case Western Reserve University)H-Index: 93
Abstract Carnitine palmitoyltransferase 1a (CPT1a) in liver mitochondrial outer membrane (MOM) catalyzes the primary regulated step in overall mitochondrial fatty acid oxidation. It has been suggested that the fundamental unit of CPT1a exists as a trimer, which under native conditions could form a dimer of the trimers creating a hexamer channel for acylcarnitine translocation. To examine the state of CPT1a in the MOM, we employed here a combined approach of sizing by mass and isolation using an ...
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May 5, 2011·PLOS ONE3.24
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Hepatitis B virus X protein (HBx) plays important roles in the development of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) contribute to cancer development by acting as oncogenes or tumor suppressors. Previously, we reported that HBx was able to promote the migration of hepatoma HepG2 cells. However, the regulation of miRNAs in the development of HBV-related HCC is poorly understood. In the present study, we reported that miR-29a was a novel regulator of migration of hepatoma cells mediate...
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Background Mammary carcinomas have been associated with a high-fat diet, and the rate of breast cancer in overweight post-menopausal women is up to 50% higher than in their normal-weight counterparts. Epidemiological studies suggest that prolactin (PRL) plays a role in the progression of breast cancer. The current study examined breast cancer as a metabolic disease in the context of altered fatty acid catabolism by examining the effect of PRL on carnitine palmitoyl transferase 1 (CPT1), an enzym...
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The purpose of this study was to evaluate changes of very low-density lipoprotein (VLDL) components in hepatic blood (HB) from 5 nonlactating nonpregnant cows fasted from days 0 to 3 and subsequently refed to day 10 and, in addition, to assess those of other lipoproteins. Increased phospholipid concentrations in each lipoprotein after the start of fasting suggested their availability for the surface lipids of lipoproteins. Although the VLDL-triglyceride (TG) concentration in HB from all cows inc...
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Apolipoprotein (apo) E is a 34.2 kDa glycoprotein synthesized by the liver and to a lesser extent by peripheral tissues (1). It is associated in plasma with triglyceride-rich lipoproteins (TRL) and HDL particles (2). ApoE plays a central role in mediating hepatic recognition and uptake of TRL and their remnants by acting as a ligand for lipoprotein binding to the LDL receptor, LDL receptor-related protein, and glycosaminoglycans (3). ApoE may also activate enzymes involved in lipoprotein metabol...
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Microsomal triglyceride transfer protein (MTP) is required for the assembly and secretion of apolipopro- tein (apo) B-containing lipoproteins. Previously, we demon- strated that the N-terminal 1,000 residues of apoB (apoB:1000) are necessary for the initiation of apoB-con- taining lipoprotein assembly in rat hepatoma McA-RH7777 cells and that these particles are phospholipid (PL) rich. To determine if the PL transfer activity of MTP is suffi cient for the assembly and secretion of primordial apo...
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This study evaluated the relationship between severity of fatty liver and macromineral status in downer dairy cows and determined the usefulness of selected biochemical analytes for assessing prognosis. Blood and liver biopsy specimens were obtained from 36 Holstein downer cows shortly after the cows became recumbent and before they were treated. Liver tissue was examined histologically and serum activity of liver-derived enzymes and concentration of total lipids, triglycerides, bile acids, gluc...
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Insulin signaling in the liver leads to accumulation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Deletion of the phosphatase Pten (phosphatase and tensin homologue deleted on chromosome 10) reduces PIP3 levels and leads to fatty liver development. The purpose of this study was to investigate the mechanisms underlying lipogenesis that result from PIP3 accumulation using liver Pten-deletion mice. To explore the role of AKT2, the major liver AKT isoform in steatosis induced by deletion of...
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