Recombinant Mouse Resistin Protein, CF

Resistin (resistance-to-insulin), also known as adipocyte-specific secretory factor (ADSF) and found in inflammatory zone 3 (FIZZ3), is a 10 kDa member of a small family of secreted cysteine-rich peptide hormones. These molecules purportedly play some role in inflammation, glucose metabolism, and angiogenesis (1, 2, 3, 4). Mouse Resistin precursor is 114 amino acids (aa) in length. It contains a 20 aa signal sequence plus a 94 aa mature region. The mature region shows an N-terminal alpha-helical tail (aa 27 - 48) and a C-terminal beta-sheet globular head (aa 51 - 112) (5, 6). The Resistin molecule circulates as either a noncovalent trimer (minor form), or a disulfide-linked homohexamer (major form). Noncovalent trimers are generated when the alpha-helical segments self-associate to form a three-stranded coiled-coil structure. Covalent hexamers subsequently appear when the free Cys at position #26 is engaged by adjacent trimers. It is hypothesized that the hexamer is a less active form of the molecule, and bioactivity is achieved at the target site by disulfide bond reduction (5). Although Resistin family molecules can noncovalently interact to form heterotrimers in vitro, there is no evidence to suggest this occurs in vivo with Resistin (7, 8). Mature mouse Resistin shares 72% and 56% aa identity with rat and human Resistin, respectively. Rat Resistin possesses an alternate start site at Met48; this Met is not found in the mouse molecule, however (9). Rodent Resistin is expressed by white adipocytes, splenocytes, astrocytes, and anterior pituitary epithelium (6, 10, 11). Although the function of Resistin is unclear, it would seem to block insulin-stimulated uptake of glucose by adipocytes, and promote glucose release by hepatocytes (6, 12, 13). As such, it has been proposed to participate in diet-induced insulin-sensitivity. Diets high in fat promote an increase in overall adipocyte size. Hypertrophic adipocytes are known to secrete TNF-alpha, which acts locally to block ACRP30 production. Since ACRP30 is an insulin-sensitizer, a drop in ACRP30 availability leads to insulin-insensitivity, which drives increased insulin production (a compensatory mechanism). High insulin induces Resistin secretion, which now antagonizes insulin action, prompting more insulin production, and more Resistin secretion (14).