Diabetes, Vol 39, Issue 12 1569-1574, Copyright © 1990 by American Diabetes Association

ARTICLES

Tumor necrosis factor-increased hepatic very-low-density lipoprotein production and increased serum triglyceride levels in diabetic rats

KR Feingold, M Soued, S Adi, I Staprans, J Shigenaga, W Doerrler, A Moser and C Grunfeld
Department of Medicine, University of California, San Francisco.

Previous studies demonstrated that administration of tumor necrosis factor (TNF) to diabetic rats rapidly increases serum triglyceride levels and stimulates hepatic lipogenesis without affecting the activity of adipose tissue lipoprotein lipase or serum insulin levels. The purpose of this study was to determine the mechanism by which TNF increases serum triglyceride levels and stimulates hepatic fatty acid synthesis in diabetic animals. The maximal increase (approximately 2-fold) in serum triglyceride levels in diabetic rats is seen with a dose of 10 micrograms TNF/200 g body wt, and the half-maximal effect is observed with 5 micrograms TNF/200 g body wt. The clearance of labeled triglyceride-rich lipoproteins from the circulation is not affected by TNF administration (triglyceride t 1/2; diabetic vs. TNF-administered diabetic, 3.5 +/- 0.7 vs. 4.0 +/- 0.6 min, respectively; NS). The production of triglyceride, measured by the Triton WR-1339 technique, is increased twofold in diabetic animals after TNF administration. These results indicate that the rapid increase in serum triglyceride levels after TNF treatment is accounted for by increased hepatic lipoprotein secretion. TNF administration did not alter either the amount or activation state of hepatic acetyl-CoA carboxylase, a key regulatory enzyme in fatty acid synthesis. There was also no change in the hepatic levels of fatty acyl-CoA, an allosteric inhibitor of acetyl-CoA carboxylase. However, there was a 71% increase in hepatic citrate concentrations. Citrate is an allosteric activator of acetyl-CoA carboxylase, and changes in hepatic citrate concentrations have been shown to mediate changes in the rates of fatty acid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. Qin, R. A. Anderson, and K. Adeli Tumor necrosis factor-{alpha} directly stimulates the overproduction of hepatic apolipoprotein B100-containing VLDL via impairment of hepatic insulin signaling Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1120 - G1129. [Abstract] [Full Text] [PDF]

				B. Qin, W. Qiu, R. K. Avramoglu, and K. Adeli Tumor Necrosis Factor-{alpha} Induces Intestinal Insulin Resistance and Stimulates the Overproduction of Intestinal Apolipoprotein B48-Containing Lipoproteins Diabetes, February 1, 2007; 56(2): 450 - 461. [Abstract] [Full Text] [PDF]

				N. Sato, K. Kobayashi, T. Inoguchi, N. Sonoda, M. Imamura, N. Sekiguchi, N. Nakashima, and H. Nawata Adenovirus-Mediated High Expression of Resistin Causes Dyslipidemia in Mice Endocrinology, January 1, 2005; 146(1): 273 - 279. [Abstract] [Full Text] [PDF]

				W. Khovidhunkit, M.-S. Kim, R. A. Memon, J. K. Shigenaga, A. H. Moser, K. R. Feingold, and C. Grunfeld Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host J. Lipid Res., July 1, 2004; 45(7): 1169 - 1196. [Abstract] [Full Text] [PDF]

				C E Bolton, A A Ionescu, W D Evans, R J Pettit, and D J Shale Altered tissue distribution in adults with cystic fibrosis Thorax, October 1, 2003; 58(10): 885 - 889. [Abstract] [Full Text] [PDF]

				L. Benthem, K. Keizer, C. H. Wiegman, S. F. de Boer, J. H. Strubbe, A. B. Steffens, F. Kuipers, and A. J. W. Scheurink Excess portal venous long-chain fatty acids induce syndrome X via HPA axis and sympathetic activation Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1286 - E1293. [Abstract] [Full Text] [PDF]