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Full-Text Articles in Medicine and Health Sciences
The Lipogenic Enzymes Dgat1, Fas, And Lpl In Adipose Tissue: Effects Of Obesity, Insulin Resistance, And Tzd Treatment, Gouri Ranganathan, Resat Unal, Irina D. Pokrovskaya, Aiwei Yao-Borengasser, Bounleut Phanavanh, Beata Lecka-Czernik, Neda Rasouli, Philip A. Kern
The Lipogenic Enzymes Dgat1, Fas, And Lpl In Adipose Tissue: Effects Of Obesity, Insulin Resistance, And Tzd Treatment, Gouri Ranganathan, Resat Unal, Irina D. Pokrovskaya, Aiwei Yao-Borengasser, Bounleut Phanavanh, Beata Lecka-Czernik, Neda Rasouli, Philip A. Kern
Clinical and Translational Science Faculty Publications
Acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS), and LPL are three enzymes important in adipose tissue triglyceride accumulation. To study the relationship of DGAT1, FAS, and LPL with insulin, we examined adipose mRNA expression of these genes in subjects with a wide range of insulin sensitivity (SI). DGAT1 and FAS (but not LPL) expression were strongly correlated with SI. In addition, the expression of DGAT1 and FAS (but not LPL) were higher in normal glucose-tolerant subjects compared with subjects with impaired glucose tolerance (IGT) (P < 0.005). To study the effects of insulin sensitizers, subjects with IGT were treated with pioglitazone or metformin for 10 weeks, and lipogenic enzymes were measured in adipose tissue. After pioglitazone treatment, DGAT1 expression was increased by 33 ± 10% (P < 0.05) and FAS expression increased by 63 ± 8% (P < 0.05); however, LPL expression was not altered. DGAT1, FAS, and LPL mRNA expression were not significantly changed after metformin treatment. The treatment of mice with rosiglitazone also resulted in an increase in adipose expression of DGAT1 by 2- to 3-fold, as did the treatment of 3T3 F442A adipocytes in vitro with thiazolidinediones. These data support a more global concept suggesting that adipose lipid storage functions to prevent peripheral lipotoxicity.
Transgenic Mice Expressing Lipoprotein Lipase In Adipose Tissue: Absence Of The Proximal 3′-Untranslated Region Causes Translational Upregulation, Lori L. Hensley, Gouri Ranganathan, Elke M. Wagner, Brian D. Wells, Joseph C. Daniel, Diane Vu, Clay F. Semenkovich, Rudolf Zechner, Philip A. Kern
Transgenic Mice Expressing Lipoprotein Lipase In Adipose Tissue: Absence Of The Proximal 3′-Untranslated Region Causes Translational Upregulation, Lori L. Hensley, Gouri Ranganathan, Elke M. Wagner, Brian D. Wells, Joseph C. Daniel, Diane Vu, Clay F. Semenkovich, Rudolf Zechner, Philip A. Kern
Clinical and Translational Science Faculty Publications
Lipoprotein lipase (LPL) is a key enzyme in lipoprotein and adipocyte metabolism. Defects in LPL can lead to hypertriglyceridemia and the subsequent development of atherosclerosis. The mechanisms of regulation of this enzyme are complex and may occur at multiple levels of gene expression. Because the 3′-untranslated region (UTR) is involved in LPL translational regulation, transgenic mice were generated with adipose tissue expression of an LPL construct either with or without the proximal 3′-UTR and driven by the aP2 promoter. Both transgenic mouse colonies were viable and expressed the transgene, resulting in a 2-fold increase in LPL activity in white adipose …
Role Of Protein Kinase C In The Translational Regulation Of Lipoprotein Lipase In Adipocytes, Gouri Ranganathan, Rami Kaakaji, Philip A. Kern
Role Of Protein Kinase C In The Translational Regulation Of Lipoprotein Lipase In Adipocytes, Gouri Ranganathan, Rami Kaakaji, Philip A. Kern
Clinical and Translational Science Faculty Publications
The hypertriglyceridemia of diabetes is accompanied by decreased lipoprotein lipase (LPL) activity in adipocytes. Although the mechanism for decreased LPL is not known, elevated glucose is known to increase diacylglycerol, which activates protein kinase C (PKC). To determine whether PKC is involved in the regulation of LPL, we studied the effect of 12-O-tetradecanoyl phorbol 13-acetate (TPA) on adipocytes. LPL activity was inhibited when TPA was added to cultures of 3T3-F442A and rat primary adipocytes. The inhibitory effect of TPA on LPL activity was observed after 6 h of treatment, and was observed at a concentration of 6 nM. …
Potential Role Of Tnfα And Lipoprotein Lipase As Candidate Genes For Obesity, Philip A. Kern
Potential Role Of Tnfα And Lipoprotein Lipase As Candidate Genes For Obesity, Philip A. Kern
Clinical and Translational Science Faculty Publications
To maintain body weight, metabolic efficiency was promoted during evolution; two candidate genes for body weight regulation are lipoprotein lipase (LPL) and tumor necrosis factor-α [TNFα). Human fat cells do not synthesize lipid, but rely on LPL-mediated plasma triglyceride hydrolysis. Adipose LPL is elevated in obesity. Following weight loss, LPL is elevated further, suggesting attempts to maintain lipid stores during fasting and to replenish lipid stores during refeeding. Muscle LPL is regulated inversely to adipose LPL. Thus, an increased adipose/muscle LPL ratio would partition dietary lipid into adipose tissue and would explain some of the variability in weight gain when …