This Article Full Text Full Text (PDF) All Versions of this Article: 147/2/943    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, D. Articles by Pagliassotti, M. J. Search for Related Content PubMed PubMed Citation Articles by Wang, D. Articles by Pagliassotti, M. J.

Saturated Fatty Acids Promote Endoplasmic Reticulum Stress and Liver Injury in Rats with Hepatic Steatosis

Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado 80523

Address all correspondence and requests for reprints to: Michael Pagliassotti, Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado 80523-1571. E-mail: pagliasm{at}cahs.colostate.edu.

Nonalcoholic fatty liver disease is a relatively new hepatic sequela of obesity and type 2 diabetes. The pathogenesis of liver injury and disease progression in nonalcoholic fatty liver disease, however, is poorly understood. The present study examined the hypothesis that the composition of fatty acids in the steatotic liver promotes liver injury. Using dietary models of hepatic steatosis characterized by similar accumulation of total triglyceride but different composition of fatty acids, we show that hepatic steatosis characterized by increased saturated fatty acids is associated with increased liver injury and markers of endoplasmic reticulum stress (e.g. X-box binding protein-1 mRNA splicing and glucose-regulated protein 78 expression). These changes preceded and/or occurred independently of obesity and differences in leptin, TNF, insulin action, and mitochondrial function. In addition, hepatic steatosis characterized by increased saturated fatty acids reduced proliferative capacity in response to partial hepatectomy and increased liver injury in response to lipopolysaccharide. These data suggest that the composition of fatty acids in the steatotic liver is an important determinant of susceptibility to liver injury.

This article has been cited by other articles:

				D. A. Cunha, P. Hekerman, L. Ladriere, A. Bazarra-Castro, F. Ortis, M. C. Wakeham, F. Moore, J. Rasschaert, A. K. Cardozo, E. Bellomo, et al. Initiation and execution of lipotoxic ER stress in pancreatic {beta}-cells J. Cell Sci., July 15, 2008; 121(14): 2308 - 2318. [Abstract] [Full Text] [PDF]

				M. T. Flowers, M. P. Keller, Y. Choi, H. Lan, C. Kendziorski, J. M. Ntambi, and A. D. Attie Liver gene expression analysis reveals endoplasmic reticulum stress and metabolic dysfunction in SCD1-deficient mice fed a very low-fat diet Physiol Genomics, May 1, 2008; 33(3): 361 - 372. [Abstract] [Full Text] [PDF]

				D. L. Eizirik, A. K. Cardozo, and M. Cnop The Role for Endoplasmic Reticulum Stress in Diabetes Mellitus Endocr. Rev., February 1, 2008; 29(1): 42 - 61. [Abstract] [Full Text] [PDF]

				J. N. Baumgardner, K. Shankar, L. Hennings, T. M. Badger, and M. J. J. Ronis A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G27 - G38. [Abstract] [Full Text] [PDF]

				Y. Xie, J. Luo, S. Kennedy, and N. O. Davidson Conditional Intestinal Lipotoxicity in Apobec-1-/- Mttp-IKO Mice: A SURVIVAL ADVANTAGE FOR MAMMALIAN INTESTINAL APOLIPOPROTEIN B mRNA EDITING J. Biol. Chem., November 9, 2007; 282(45): 33043 - 33051. [Abstract] [Full Text] [PDF]

				A. M Zivkovic, J B. German, and A. J Sanyal Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease Am. J. Clinical Nutrition, August 1, 2007; 86(2): 285 - 300. [Abstract] [Full Text] [PDF]

				M. J. Pagliassotti, Y. Wei, and D. Wang Insulin Protects Liver Cells from Saturated Fatty Acid-Induced Apoptosis via Inhibition of c-Jun NH2 Terminal Kinase Activity Endocrinology, July 1, 2007; 148(7): 3338 - 3345. [Abstract] [Full Text] [PDF]

				H. Sampath, M. Miyazaki, A. Dobrzyn, and J. M. Ntambi Stearoyl-CoA Desaturase-1 Mediates the Pro-lipogenic Effects of Dietary Saturated Fat J. Biol. Chem., January 26, 2007; 282(4): 2483 - 2493. [Abstract] [Full Text] [PDF]

				N. M. Borradaile, X. Han, J. D. Harp, S. E. Gale, D. S. Ory, and J. E. Schaffer Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death J. Lipid Res., December 1, 2006; 47(12): 2726 - 2737. [Abstract] [Full Text] [PDF]

				K. Staiger, H. Staiger, C. Weigert, C. Haas, H.-U. Haring, and M. Kellerer Saturated, but Not Unsaturated, Fatty Acids Induce Apoptosis of Human Coronary Artery Endothelial Cells via Nuclear Factor-{kappa}B Activation Diabetes, November 1, 2006; 55(11): 3121 - 3126. [Abstract] [Full Text] [PDF]

				Y. Wei, D. Wang, F. Topczewski, and M. J. Pagliassotti Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E275 - E281. [Abstract] [Full Text] [PDF]