This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chang, B. H.-J.
Right arrow Articles by Chan, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chang, B. H.-J.
Right arrow Articles by Chan, L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2006, p. 1063-1076, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.1063-1076.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Protection against Fatty Liver but Normal Adipogenesis in Mice Lacking Adipose Differentiation-Related Protein{dagger}

Benny Hung-Junn Chang,1 Lan Li,1 Antoni Paul,2 Susumu Taniguchi,2,{ddagger} Vijayalakshmi Nannegari,3 William C. Heird,3 and Lawrence Chan1,2*

Department of Molecular and Cellular Biology,1 Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine,2 Department of Pediatrics-Nutrition, Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas 770303

Received 18 October 2005/ Accepted 9 November 2005

Adipose differentiation-related protein (ADFP; also known as ADRP or adipophilin), is a lipid droplet (LD) protein found in most cells and tissues. ADFP expression is strongly induced in cells with increased lipid load. We have inactivated the Adfp gene in mice to better understand its role in lipid accumulation. The Adfp-deficient mice have unaltered adipose differentiation or lipolysis in vitro or in vivo. Importantly, they display a 60% reduction in hepatic triglyceride (TG) and are resistant to diet-induced fatty liver. To determine the mechanism for the reduced hepatic TG content, we measured hepatic lipogenesis, very-low-density lipoprotein (VLDL) secretion, and lipid uptake and utilization, all of which parameters were shown to be similar between mutant and wild-type mice. The finding of similar VLDL output in the presence of a reduction in total TG in the Adfp-deficient liver is explained by the retention of TG in the microsomes where VLDL is assembled. Given that lipid droplets are thought to form from the outer leaflet of the microsomal membrane, the reduction of TG in the cytosol with concomitant accumulation of TG in the microsome of Adfp–/– cells suggests that ADFP may facilitate the formation of new LDs. In the absence of ADFP, impairment of LD formation is associated with the accumulation of microsomal TG but a reduction in TG in other subcellular compartments.

* Corresponding author. Mailing address: Division of Diabetes, Endocrinology, and Metabolism, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-4478. Fax: (713) 798-8764. E-mail: lchan{at}bcm.tmc.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Division of Immunology, Hematology and Metabolic Diseases, Kyushu University Hospital at Beppu, Beppu 874-0838, Japan.

Molecular and Cellular Biology, February 2006, p. 1063-1076, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.1063-1076.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mao, J., Yang, T., Gu, Z., Heird, W. C., Finegold, M. J., Lee, B., Wakil, S. J. (2009). aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues. Proc. Natl. Acad. Sci. USA 106: 17576-17581 [Abstract] [Full Text]  
  • Meex, R. C. R., Schrauwen, P., Hesselink, M. K. C. (2009). Modulation of myocellular fat stores: lipid droplet dynamics in health and disease. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297: R913-R924 [Abstract] [Full Text]  
  • Rankin, E. B., Rha, J., Selak, M. A., Unger, T. L., Keith, B., Liu, Q., Haase, V. H. (2009). Hypoxia-Inducible Factor 2 Regulates Hepatic Lipid Metabolism. Mol. Cell. Biol. 29: 4527-4538 [Abstract] [Full Text]  
  • Sapiro, J. M., Mashek, M. T., Greenberg, A. S., Mashek, D. G. (2009). Hepatic triacylglycerol hydrolysis regulates peroxisome proliferator-activated receptor {alpha} activity. J. Lipid Res. 50: 1621-1629 [Abstract] [Full Text]  
  • Fan, B., Ikuyama, S., Gu, J.-Q., Wei, P., Oyama, J.-i., Inoguchi, T., Nishimura, J. (2009). Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells. Am. J. Physiol. Endocrinol. Metab. 297: E112-E123 [Abstract] [Full Text]  
  • Guillen, N., Navarro, M. A., Arnal, C., Noone, E., Arbones-Mainar, J. M., Acin, S., Surra, J. C., Muniesa, P., Roche, H. M., Osada, J. (2009). Microarray analysis of hepatic gene expression identifies new genes involved in steatotic liver. Physiol. Genomics 37: 187-198 [Abstract] [Full Text]  
  • Gu, J.-Q., Ikuyama, S., Wei, P., Fan, B., Oyama, J.-i., Inoguchi, T., Nishimura, J. (2008). Pycnogenol, an extract from French maritime pine, suppresses Toll-like receptor 4-mediated expression of adipose differentiation-related protein in macrophages. Am. J. Physiol. Endocrinol. Metab. 295: E1390-E1400 [Abstract] [Full Text]  
  • Tetri, L. H., Basaranoglu, M., Brunt, E. M., Yerian, L. M., Neuschwander-Tetri, B. A. (2008). Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am. J. Physiol. Gastrointest. Liver Physiol. 295: G987-G995 [Abstract] [Full Text]  
  • Urahama, Y., Ohsaki, Y., Fujita, Y., Maruyama, S., Yuzawa, Y., Matsuo, S., Fujimoto, T. (2008). Lipid Droplet-Associated Proteins Protect Renal Tubular Cells from Fatty Acid-Induced Apoptosis. Am. J. Pathol. 173: 1286-1294 [Abstract] [Full Text]  
  • Imanishi, Y., Sun, W., Maeda, T., Maeda, A., Palczewski, K. (2008). Retinyl Ester Homeostasis in the Adipose Differentiation-related Protein-deficient Retina. J. Biol. Chem. 283: 25091-25102 [Abstract] [Full Text]  
  • Varela, G. M., Antwi, D. A., Dhir, R., Yin, X., Singhal, N. S., Graham, M. J., Crooke, R. M., Ahima, R. S. (2008). Inhibition of ADRP prevents diet-induced insulin resistance. Am. J. Physiol. Gastrointest. Liver Physiol. 295: G621-G628 [Abstract] [Full Text]  
  • Bell, M., Wang, H., Chen, H., McLenithan, J. C., Gong, D.-W., Yang, R.-Z., Yu, D., Fried, S. K., Quon, M. J., Londos, C., Sztalryd, C. (2008). Consequences of Lipid Droplet Coat Protein Downregulation in Liver Cells: Abnormal Lipid Droplet Metabolism and Induction of Insulin Resistance. Diabetes 57: 2037-2045 [Abstract] [Full Text]  
  • Ohsaki, Y., Cheng, J., Suzuki, M., Fujita, A., Fujimoto, T. (2008). Lipid droplets are arrested in the ER membrane by tight binding of lipidated apolipoprotein B-100. J. Cell Sci. 121: 2415-2422 [Abstract] [Full Text]  
  • Daugherty, A., Rateri, D. L., Lu, H. (2008). As Macrophages Indulge, Atherosclerotic Lesions Bulge. Circ. Res. 102: 1445-1447 [Full Text]  
  • Paul, A., Chang, B. H.-J., Li, L., Yechoor, V. K., Chan, L. (2008). Deficiency of Adipose Differentiation-Related Protein Impairs Foam Cell Formation and Protects Against Atherosclerosis. Circ. Res. 102: 1492-1501 [Abstract] [Full Text]  
  • Schmidt, C., Gonzaludo, N. P., Strunk, S., Dahm, S., Schuchhardt, J., Kleinjung, F., Wuschke, S., Joost, H.-G., Al-Hasani, H. (2008). A meta-analysis of QTL for diabetes-related traits in rodents. Physiol. Genomics 34: 42-53 [Abstract] [Full Text]  
  • Keller, P., Petrie, J. T., De Rose, P., Gerin, I., Wright, W. S., Chiang, S.-H., Nielsen, A. R., Fischer, C. P., Pedersen, B. K., MacDougald, O. A. (2008). Fat-specific Protein 27 Regulates Storage of Triacylglycerol. J. Biol. Chem. 283: 14355-14365 [Abstract] [Full Text]  
  • Ducharme, N. A., Bickel, P. E. (2008). Minireview: Lipid Droplets in Lipogenesis and Lipolysis. Endocrinology 149: 942-949 [Abstract] [Full Text]  
  • Yan, J., Barnes, B. M., Kohl, F., Marr, T. G. (2008). Modulation of gene expression in hibernating arctic ground squirrels. Physiol. Genomics 32: 170-181 [Abstract] [Full Text]  
  • Russell, T. D., Palmer, C. A., Orlicky, D. J., Bales, E. S., Chang, B. H.-J., Chan, L., McManaman, J. L. (2008). Mammary glands of adipophilin-null mice produce an amino-terminally truncated form of adipophilin that mediates milk lipid droplet formation and secretion. J. Lipid Res. 49: 206-216 [Abstract] [Full Text]  
  • Listenberger, L. L., Ostermeyer-Fay, A. G., Goldberg, E. B., Brown, W. J., Brown, D. A. (2007). Adipocyte differentiation-related protein reduces the lipid droplet association of adipose triglyceride lipase and slows triacylglycerol turnover. J. Lipid Res. 48: 2751-2761 [Abstract] [Full Text]  
  • Kotokorpi, P., Ellis, E., Parini, P., Nilsson, L.-M., Strom, S., Steffensen, K. R., Gustafsson, J.-A., Mode, A. (2007). Physiological Differences between Human and Rat Primary Hepatocytes in Response to Liver X Receptor Activation by 3-[3-[N-(2-Chloro-3-trifluoromethylbenzyl)-(2,2-diphenylethyl)amino]propyloxy]phenylacetic Acid Hydrochloride (GW3965). Mol. Pharmacol. 72: 947-955 [Abstract] [Full Text]  
  • Li, L., Naples, M., Song, H., Yuan, R., Ye, F., Shafi, S., Adeli, K., Ng, D. S. (2007). LCAT-null mice develop improved hepatic insulin sensitivity through altered regulation of transcription factors and suppressors of cytokine signaling. Am. J. Physiol. Endocrinol. Metab. 293: E587-E594 [Abstract] [Full Text]  
  • Russell, T. D., Palmer, C. A., Orlicky, D. J., Fischer, A., Rudolph, M. C., Neville, M. C., McManaman, J. L. (2007). Cytoplasmic lipid droplet accumulation in developing mammary epithelial cells: roles of adipophilin and lipid metabolism. J. Lipid Res. 48: 1463-1475 [Abstract] [Full Text]  
  • Chang, B. H.-J., Chan, L. (2007). Regulation of Triglyceride Metabolism. III. Emerging role of lipid droplet protein ADFP in health and disease. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G1465-G1468 [Abstract] [Full Text]  
  • Wolins, N. E., Quaynor, B. K., Skinner, J. R., Tzekov, A., Croce, M. A., Gropler, M. C., Varma, V., Yao-Borengasser, A., Rasouli, N., Kern, P. A., Finck, B. N., Bickel, P. E. (2006). OXPAT/PAT-1 Is a PPAR-Induced Lipid Droplet Protein That Promotes Fatty Acid Utilization. Diabetes 55: 3418-3428 [Abstract] [Full Text]  
  • Sztalryd, C., Bell, M., Lu, X., Mertz, P., Hickenbottom, S., Chang, B. H.-J., Chan, L., Kimmel, A. R., Londos, C. (2006). Functional Compensation for Adipose Differentiation-related Protein (ADFP) by Tip47 in an ADFP Null Embryonic Cell Line. J. Biol. Chem. 281: 34341-34348 [Abstract] [Full Text]  
  • Magnusson, B., Asp, L., Bostrom, P., Ruiz, M., Stillemark-Billton, P., Linden, D., Boren, J., Olofsson, S.-O. (2006). Adipocyte Differentiation-Related Protein Promotes Fatty Acid Storage in Cytosolic Triglycerides and Inhibits Secretion of Very Low-Density Lipoproteins. Arterioscler. Thromb. Vasc. Bio. 26: 1566-1571 [Abstract] [Full Text]  
  • Yamaguchi, T., Matsushita, S., Motojima, K., Hirose, F., Osumi, T. (2006). MLDP, a Novel PAT Family Protein Localized to Lipid Droplets and Enriched in the Heart, Is Regulated by Peroxisome Proliferator-activated Receptor {alpha}. J. Biol. Chem. 281: 14232-14240 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»