Secreted by white adipose tissue as a hormone, resistin was identified as a possible link between obesity and insulin resistance. High circulating resistin levels were observed to correlate with obesity. Administration of resistin lowered the glucose tolerance threshold and impaired insulin activity; whereas anti-resistin antibodies had the opposite effects. However, contradictory data were subsequently reported in regard to the correlation between resistin expression level and obesity or type 2 diabetes. Two additional proteins that share a highly homologous C-terminus with resistin have been identified in mouse, and one in human, forming a resistin-related protein family. Resistin was shown to dimerize through a disulfide bond formed by the N-terminal-most cysteine (Cys26). Here we demonstrate that while Cys26 is both necessary and sufficient for homodimer formation, all three resistin family members can also interact with one another regardless of the presence of Cys26 through non-covalent interactions. Furthermore, protein crosslinking analysis indicated that resistin and resistin beta, but not resistin alpha, exist as multimers, probably with a dimer as the subunit. The multiple protein complex formation is obviously at a level higher than the Cys26 disulfide bonding. These results suggest the potential importance of considering intermolecular interactions among resistin family members in studying their functions.

This article has been cited by other articles:

				C. Graveleau, V. G. Zaha, A. Mohajer, R. R. Banerjee, N. Dudley-Rucker, C. M. Steppan, M. W. Rajala, P. E. Scherer, R. S. Ahima, M. A. Lazar, et al. Mouse and Human Resistins Impair Glucose Transport in Primary Mouse Cardiomyocytes, and Oligomerization Is Required for This Biological Action J. Biol. Chem., September 9, 2005; 280(36): 31679 - 31685. [Abstract] [Full Text] [PDF]

				M. Gerber, A. Boettner, B. Seidel, A. Lammert, J. Bar, E. Schuster, J. Thiery, W. Kiess, and J. Kratzsch Serum Resistin Levels of Obese and Lean Children and Adolescents: Biochemical Analysis and Clinical Relevance J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4503 - 4509. [Abstract] [Full Text] [PDF]

				S. Mandard, F. Zandbergen, N. S. Tan, P. Escher, D. Patsouris, W. Koenig, R. Kleemann, A. Bakker, F. Veenman, W. Wahli, et al. The Direct Peroxisome Proliferator-activated Receptor Target Fasting-induced Adipose Factor (FIAF/PGAR/ANGPTL4) Is Present in Blood Plasma as a Truncated Protein That Is Increased by Fenofibrate Treatment J. Biol. Chem., August 13, 2004; 279(33): 34411 - 34420. [Abstract] [Full Text] [PDF]

				K.-H. Kim, L. Zhao, Y. Moon, C. Kang, and H. S. Sul Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity PNAS, April 27, 2004; 101(17): 6780 - 6785. [Abstract] [Full Text] [PDF]