Disease relevance of Adipsin

• Severely impaired adipsin expression in genetic and acquired obesity [1].
• Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor [2].
• Adipsin expression was still normal in obese mice 15 days old but frankly deficient at 30 days of age when hyperinsulinemia has developed [3].
• The precise mechanisms by which weight loss occurs are currently being elucidated and probably involve the actions of classic hormones as well as cytokines, such as TNF (cachectin), adipsin, and interleukin-1 and interleukin-6 [4].
• We also observed that blood adipsin concentrations can vary as a function of feeding or adiposity, in that they tend to be mildly elevated in obese individuals or mildly reduced in individuals with total lipo-atrophy, cachexia related to AIDS and anorexia nervosa [5].

Psychiatry related information on Adipsin

• Effect of body weight and caloric restriction on serum complement proteins, including Factor D/adipsin: studies in anorexia nervosa and obesity [6].
• These findings provide new information on the role of adipsin on individual differences in response to chronically elevated food intake [7].

High impact information on Adipsin

• Adipsin and complement factor D activity: an immune-related defect in obesity [8].
• Pluripotent stem cell lines were isolated with homologously recombined insertions at three different loci: c-fos, which is expressed at a low level in ES cells, and two genes, adipsin and adipocyte P2 (aP2), which are transcribed specifically in adipose cells and are not expressed at detectable levels in ES cells [9].
• Like authentic factor D, adipsin can activate the alternative pathway of complement, resulting in red blood cell lysis [8].
• Immunoblots probed with antisera to synthetic peptides identify two forms of adipsin that are synthesized and secreted by 3T3 adipocytes [10].
• Although adipsin is principally synthesized in adipose tissue, it is also produced by sciatic nerve and is found in the bloodstream [10].

Chemical compound and disease context of Adipsin

• To map the region of the adipsin gene that confers this response to obesity, transgenic mice were made containing -114, -250, -400, -700, and -938 base pairs (bp) to +35 bp of the promoter linked to the bacterial chloramphenicol acetyltransferase gene [11].
• In the present study, E+C treatment of MSG obese mice reversed obesity and markedly increased serum adipsin and adipsin mRNA levels in WAT and brown adipose tissue (BAT) [12].
• In addition, treatment of MSG obese mice with the sympathomimetic drug mixture ephedrine and caffeine restores adipsin deficiency to normal, while reversing obesity [13].
• Both feeding caffeine and restricting intake normalized serum adipsin and caused weight loss, but did not normalize the percentage of body fat [14].
• In experimental rats, increased activity of a 20 kDa serine proteinase related to adipsin precedes the development of sustained pulmonary hypertension and vascular abnormalities [15].

Biological context of Adipsin

• Because of the apparent restriction of adipsin synthesis to tissues highly active in lipid metabolism, its presence in serum, and its modulation in altered metabolic states, this molecule may play a previously unrecognized role in systemic lipid metabolism or energy balance [10].
• The PCR product was used to screen a cDNA library and sequences obtained encoded rat adipsin [16].
• These results indicate that 950 bases of the 5' flanking region of the adipsin gene carry information that specifies both expression in adipose tissue and a response to a gene or chemical that induces obesity [17].
• We have compared the DNA sequence of the 5'-flanking region of the aP2 gene to the promoter regions of two other genes activated during adipocyte differentiation, glycerol-3-phosphate dehydrogenase and adipsin, and find a 13-base region of homology (Formula: see text) present in multiple copies in the 5'-flanking region of each gene [18].
• Glucocorticoids are known to exert direct effects on gene expression; however, with respect to adipsin gene expression, a direct effect has not been found [19].

Anatomical context of Adipsin

• Immunogold labeling with an antibody to an adipsin peptide sequence localized EVE to PA smooth muscle cells [16].
• Additionally, the aberrant expression of adipsin, and its presence in feces may serve as a noninvasive biomarker of gastrointestinal toxicity associated with perturbed Notch signaling [2].
• Microarray analysis of ileum from FGSI-treated rats revealed differential expression responses in a number of genes indicative of Notch signaling perturbation, including the serine protease adipsin [2].
• A major role for the adrenal gland and adrenal glucocorticoids in the aberrant regulation of adipsin in these models of obesity is indicated by several experiments [20].
• An intact microtubule network is specifically required for insulin-mediated GLUT4 translocation since nocodazole treatment did not affect insulin-mediated GLUT1 translocation or adipsin secretion [21].

Associations of Adipsin with other chemical compounds

• Our results suggest the existence of at least two distinct pathways that undergo insulin-stimulated exocytosis in 3T3-L1 adipocytes, one for adipsin release and one for glucose transporter translocation [22].
• Transgenic mice containing as few as 114 bp of the adipsin promoter had high levels of chloramphenicol acetyltransferase activity in adipose tissue [11].
• Corticosterone administration also causes suppression in the levels of adipsin mRNA and protein in lean mice, although this decrease is never as severe as that seen in obese mice [20].
• The level of adipsin RNA is dramatically decreased by hormone treatment, but the change occurs more slowly than for other fat cell mRNAs, such as glycerophosphate dehydrogenase [23].
• As reported, all TZDs we tested (troglitazone, pioglitazone, and BRL 49653) markedly increased the number of Oil Red O-positive adipocytes and the expression of adipsin and PPARgamma 2 [24].

Gene context of Adipsin

• Additional studies in 3T3-L1 preadipocytes demonstrate that this FGSI inhibits Hes-1 expression while up-regulating adipsin expression [2].
• Low level constitutive expression of PPAR gamma in 3T3-L1 adipocytes (at levels approximately 2- to 3-fold higher than in preadipocytes) partially blocked the inhibitory effect of TNF alpha on aP2 and adipsin expression [25].
• While tissue plasminogen activator (tPA) and adipsin, an adipocyte derived protease, were unaffected by LIP, changes in soluble vascular cell adhesion molecule-1 (sVCAM-1) were significantly correlated (p = 0.02) with those seen for PAI-1 [26].
• RESULTS: Leptin (Lep) and adipsin expressions had the greatest fold differences between obese and lean mice [27].
• We show that the gene encoding CETP is expressed in preadipocytes and is present throughout differentiation as compared to LPL and adipsin which were detected in the majority of samples by day 2 or 3 of adipogenesis [28].

Analytical, diagnostic and therapeutic context of Adipsin

• Circulating adipsin protein is decreased in these animal models of obesity, as determined by immunoblotting with antisera to adipsin [1].
• Northern blot analysis showed that, following a 24-h exposure of 3T3-F442A adipocytic cultures to RA (10 microM), there was a 4-5-fold decrease of adipsin mRNA level [29].
• Adrenalectomy of the ob/ob mouse raises the circulating levels of adipsin protein and the amount of this mRNA in epididymal fat pads (5-fold), although neither is increased to the levels seen in lean controls [20].
• Using gel retardation assays, we showed that a 56-bp fragment of DNA mapping between -687 and -743 bp upstream from the start of adipsin expression was bound by protein factors in nuclear extracts prepared from adipose tissue [11].
• We were able to show that FGSI-treated rats had elevated levels of adipsin protein in gastrointestinal contents and feces, and by immunohistochemistry demonstrated that adipsin containing ileum crypt cells were increased in FGSI-treated rats [2].

References