HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/E576    most recent 00523.2006v2 00523.2006v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Guo, W. Articles by Luo, Z. Search for Related Content PubMed PubMed Citation Articles by Guo, W. Articles by Luo, Z.

Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes

¹Department of Medicine and ²Department of Genetics and Genomics, Boston University School of Medicine, Boston, Massachusetts

Submitted 26 September 2006 ; accepted in final form 9 May 2007

Although fatty acids enhance preadipocyte differentiation in the presence of adequate hormone cocktails, little is known regarding their effects in the absence of these hormones. We have now shown that palmitate, a common long-chain saturated fatty acid, induced apoptosis in both mouse 3T3-L1 and rat primary preadipocytes grown in a normal serum-containing medium. Treatment of preadipocytes with palmitate induced multiple endoplasmic reticulum (ER) stress responses, evidenced by increased protein content of CHOP and GRP78 and splicing of XBP-1 mRNA, as well as altered phosphorylation of eIF2 and increased phosphorylation of JNK and Erk1/2. Intriguingly, palmitate induced an early activation of Akt but diminished both Akt activation and its protein mass after prolonged incubation (>6 h). In association with these changes, palmitate reduced expression of -catenin and its downstream target, c-Myc and cyclin D1, two key prosurvival proteins. Overexpression of constitutively active Akt did not block the apoptotic effect of palmitate. Cotreatment with unsaturated fatty acids (oleate, linoleate) or with LiCl (a glycogen synthase kinase-3 inhibitor) attenuated the palmitate-induced apoptosis. Subsequent analysis suggested that the unsaturated fatty acids probably counteracted palmitate by reducing, not eliminating, ER stress, whereas LiCl probably improved viability by activating the Wnt signaling pathway. Cotreatment of palmitate with a standard adipogenic hormone cocktail also abolished the apoptotic effect and promoted adipocyte differentiation. Collectively, our results suggest that palmitate causes multiple cellular stresses that may lead to apoptosis in preadipocytes in the absence of adipogenic stimuli, highlighting the importance of exogenous hormones in directing cell fate in response to increased fatty acid influx.

insulin-like growth factor-1 signaling; Wnt signaling

This article has been cited by other articles:

				Q. G. Zhou, M. Zhou, F. F. Hou, and X. Peng Asymmetrical dimethylarginine triggers lipolysis and inflammatory response via induction of endoplasmic reticulum stress in cultured adipocytes Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E869 - E878. [Abstract] [Full Text] [PDF]

				A. S. Molgat, A. Gagnon, and A. Sorisky Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner Am J Physiol Cell Physiol, April 1, 2009; 296(4): C757 - C765. [Abstract] [Full Text] [PDF]

				A. Kennedy, K. Martinez, C.-C. Chuang, K. LaPoint, and M. McIntosh Saturated Fatty Acid-Mediated Inflammation and Insulin Resistance in Adipose Tissue: Mechanisms of Action and Implications J. Nutr., January 1, 2009; 139(1): 1 - 4. [Abstract] [Full Text] [PDF]

				C.-L. E. Yen, S. J. Stone, S. Koliwad, C. Harris, and R. V. Farese Jr. Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis J. Lipid Res., November 1, 2008; 49(11): 2283 - 2301. [Abstract] [Full Text] [PDF]

				T.-S. Park, Y. Hu, H.-L. Noh, K. Drosatos, K. Okajima, J. Buchanan, J. Tuinei, S. Homma, X.-C. Jiang, E. D. Abel, et al. Ceramide is a cardiotoxin in lipotoxic cardiomyopathy J. Lipid Res., October 1, 2008; 49(10): 2101 - 2112. [Abstract] [Full Text] [PDF]

				S. K. Das, W. S. Chu, A. K. Mondal, N. K. Sharma, P. A. Kern, N. Rasouli, and S. C. Elbein Effect of pioglitazone treatment on endoplasmic reticulum stress response in human adipose and in palmitate-induced stress in human liver and adipose cell lines Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E393 - E400. [Abstract] [Full Text] [PDF]

				W. Guo, J. Flanagan, R. Jasuja, J. Kirkland, L. Jiang, and S. Bhasin The Effects of Myostatin on Adipogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells Are Mediated through Cross-communication between Smad3 and Wnt/{beta}-Catenin Signaling Pathways J. Biol. Chem., April 4, 2008; 283(14): 9136 - 9145. [Abstract] [Full Text] [PDF]