This Article Full Text (PDF) 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 book 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 Bradley, R. L. Articles by Cheatham, B. Search for Related Content PubMed PubMed Citation Articles by Bradley, R. L. Articles by Cheatham, B.

The Adipocyte as a Secretory Organ: Mechanisms of Vesicle Transport and Secretory Pathways

Research Division, Joslin Diabetes Center and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215

ABSTRACT

Obesity is a common problem in western society that is directly linked to several disease processes and is associated with significant morbidity and mortality. Adipocytes — the primary site for energy storage (as triglycerides) and release — were long suspected to have an active role in regulating body weight homeostasis and energy balance. As a result, many studies have focused on finding abnormalities in adipocyte physiology and metabolism. An ever-increasing body of evidence indicates that, in addition to serving as a repository for energy reserves, adipocytes secrete a myriad of factors that comprise a complex network of endocrine, autocrine, and paracrine signals. Very little is known regarding the molecular mechanisms utilized by the adipocyte in regulating the biosynthesis and exocytosis of these secreted products. In order to gain a better understanding of these processes, we have examined the two classical secretory pathways: regulated and constitutive. Using leptin as a model adipocyte-secretory protein, this review focuses primarily on the latter pathway. This includes regulation of leptin synthesis and secretion by insulin and glucocorticoids and, more recently, the finding that the orexigenic neuropeptide, melanin-concentrating hormone (MCH), can stimulate leptin synthesis and secretion. This chapter also incorporates new data describing the partial purification and effect of insulin on leptin-containing vesicles in rat adipocytes. These data indicate that the majority of leptin trafficking occurs via a constitutive secretory pathway and that the primary acute insulin effect on leptin secretion is to increase leptin protein content. In addition, we describe the identification and characterization of the vesicle-associated protein, pantophysin, which may play a multifunctional role in vesicle biogenesis and transport.

This article has been cited by other articles:

				J. Y. Kim, K. Liu, S. Zhou, K. Tillison, Y. Wu, and C. M. Smas Assessment of fat-specific protein 27 in the adipocyte lineage suggests a dual role for FSP27 in adipocyte metabolism and cell death Am J Physiol Endocrinol Metab, April 1, 2008; 294(4): E654 - E667. [Abstract] [Full Text] [PDF]

				J. Y. Kim, Y. Wu, and C. M. Smas Characterization of ScAP-23, a new cell line from murine subcutaneous adipose tissue, identifies genes for the molecular definition of preadipocytes Physiol Genomics, October 19, 2007; 31(2): 328 - 342. [Abstract] [Full Text] [PDF]

				N. Akhter, B. W. Johnson, C. Crane, M. Iruthayanathan, Y.-H. Zhou, A. Kudo, and G. V. Childs Anterior Pituitary Leptin Expression Changes in Different Reproductive States: In Vitro Stimulation by Gonadotropin-releasing Hormone J. Histochem. Cytochem., February 1, 2007; 55(2): 151 - 166. [Abstract] [Full Text] [PDF]

				A. Xu, K. W. Chan, R. L. C. Hoo, Y. Wang, K. C. B. Tan, J. Zhang, B. Chen, M. C. Lam, C. Tse, G. J. S. Cooper, et al. Testosterone Selectively Reduces the High Molecular Weight Form of Adiponectin by Inhibiting Its Secretion from Adipocytes J. Biol. Chem., May 6, 2005; 280(18): 18073 - 18080. [Abstract] [Full Text] [PDF]

				T. G. Ramsay and M. P. Richards Hormonal regulation of leptin and leptin receptor expression in porcine subcutaneous adipose tissue J Anim Sci, December 1, 2004; 82(12): 3486 - 3492. [Abstract] [Full Text] [PDF]

				G. Lee and J. H. Park Hemolymph Sugar Homeostasis and Starvation-Induced Hyperactivity Affected by Genetic Manipulations of the Adipokinetic Hormone-Encoding Gene in Drosophila melanogaster Genetics, May 1, 2004; 167(1): 311 - 323. [Abstract] [Full Text] [PDF]

				M. A. El-Haddad, M. Desai, D. Gayle, and M. G. Ross In Utero Development of Fetal Thirst and Appetite: Potential for Programming Reproductive Sciences, April 1, 2004; 11(3): 123 - 130. [Abstract] [PDF]

				K. Rahmouni and W. G. Haynes Leptin and the Cardiovascular System Recent Prog. Horm. Res., January 1, 2004; 59(1): 225 - 244. [Abstract] [Full Text]

				I. Lefrere, P. de Coppet, J.-C. Camelin, S. Le Lay, N. Mercier, N. Elshourbagy, A. Bril, I. Berrebi-Bertrand, B. Feve, and S. Krief Neuropeptide AF and FF Modulation of Adipocyte Metabolism. PRIMARY INSIGHTS FROM FUNCTIONAL GENOMICS AND EFFECTS ON beta -ADRENERGIC RESPONSIVENESS J. Biol. Chem., October 11, 2002; 277(42): 39169 - 39178. [Abstract] [Full Text] [PDF]

				D. Hamerman Molecular-Based Therapeutic Approaches in Treatment of Anorexia of Aging and Cancer Cachexia J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2002; 57(8): M511 - 518. [Abstract] [Full Text] [PDF]

				Y. Wang, A. Xu, C. Knight, L. Y. Xu, and G. J. S. Cooper Hydroxylation and Glycosylation of the Four Conserved Lysine Residues in the Collagenous Domain of Adiponectin. POTENTIAL ROLE IN THE MODULATION OF ITS INSULIN-SENSITIZING ACTIVITY J. Biol. Chem., May 24, 2002; 277(22): 19521 - 19529. [Abstract] [Full Text] [PDF]

				N. Takahashi, T. Kawada, T. Yamamoto, T. Goto, A. Taimatsu, N. Aoki, H. Kawasaki, K. Taira, K. K. Yokoyama, Y. Kamei, et al. Overexpression and Ribozyme-mediated Targeting of Transcriptional Coactivators CREB-binding Protein and p300 Revealed Their Indispensable Roles in Adipocyte Differentiation through the Regulation of Peroxisome Proliferator-activated Receptor gamma J. Biol. Chem., May 3, 2002; 277(19): 16906 - 16912. [Abstract] [Full Text] [PDF]

				A. G. Comuzzie, T. Funahashi, G. Sonnenberg, L. J. Martin, H. J. Jacob, A. E. K. Black, D. Maas, M. Takahashi, S. Kihara, S. Tanaka, et al. The Genetic Basis of Plasma Variation in Adiponectin, a Global Endophenotype for Obesity and the Metabolic Syndrome J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4321 - 4325. [Abstract] [Full Text] [PDF]