|
|
|
|
Adipsin, Pref-1, and C1q Antibodies
Adipose tissue is the largest reservoir of fuel, storing energy in the form of rapidly utilizable triglycerides. Adipocytes synthesize and store energy in periods of nutritional abundance and mobilize lipids during starvation and other times of need. The switch from energy storage to expenditure is finely regulated by a variety of hormones. In order to accomplish these complex tasks energy balance, adipocytes express many genes involved in lipid metabolism and glucose homeostasis. Some of the these genes include fatty acid synthase, fatty acid binding protein aP2, lipoprotein lipase, phosphoenolpyruvate carboxy kinase, malic enzymes, glyceralduhyde-3-phosphate dehydrogenase, glut-4, IGF-1, insulin receptors, TNF-a, the product of obese gene leptin, resistins, Adipsin, Acrp30, Uncoupling proteins (UCPs), PPARs, pref-1, among others. Many of these genes are finely regulated during adipocyte differentiation and maturation. Several adipocyte-derived proteins act in an autocrine or paracrine fashion to control its own and other cell's cellular physiology. Adipsin is serine protease that is secreted by adipocytes. It is deficient in several animal model of obesity. Adipsin has now been identified as the same protein as complement factor D. Adipsin, also called ADN or complement factor D or C3 convertase activator or properdin factor D (precursors: mouse 259-aa; rat 263 aa, human 253 aa, mature protein 26-253, ~22 kDa) cleaves factor B when the latter is complexed with factor C3B, activating the C3BB complex, which then becomes C3 convertase of the alternative pathway. Adipocyte is the major protein secreted by the adipocytes. Unlike rodents, adipsin is also expressed in monocytes/macrphages. Most adipsin is secreted in blood (50 ug/ml in normal lean mice and 50-100 fold less in fat from db/db or ob/ob or MSG (monosodium glutamate-treated mice). Its expression is induced upon differentiation of preadipocytes.
Preadipocyte factor-1 (Pref-1), an epidermal growth
factor-like domain-containing transmembrane protein is implicated in inhibiting
preadipocytes differentiation. Pref-1 (mouse 385-aa, rat 383-aa, human 383-aa,
chromosome 14q32), also known as fetal antigen 1 (FA1),
Delta Drosophila homolog-like 1 (DLK1) or Zona glomerulosa-specific factor (ZOG),
is synthesized as a membrane protein in preadipocytes but it is not detectable
in mature adipocytes. Dexamethasone, a promoter of adipocyte differentiation,
down regulates Pref-1. Pref-1 is proteolytically cleaved to generate a
biologically active 50-kDa ectodomain (24-303 aa) or soluble form. Constitutive
expression of Pref-1 or addition of its ectodomain inhibits adipogenesis. There
are at least four major isoforms (45-60 kDa) of Pref-1 generated by
alternatively splicing. Pref-1/DLK is expressed in tumors with neuroendocrine
features, such as neuroblastoma, pheochromocytoma, and a subset of small cell
lung carcinoma cell lines. Its expression in normal tissues is restricted to the
adrenal gland and placenta.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|