Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipsin gene expression is severely diminished in certain forms of genetic and acquired rodent obesity. Common to many of these models of obesity is decreased sympathetic nervous system (SNS) activity. In addition, treatment of MSG obese mice with the sympathomimetic drug mixture ephedrine and caffeine restores adipsin deficiency to normal, while reversing obesity. Based on these observations, we hypothesized that adipsin gene expression might be regulated through changes in SNS activity with deficient adipsin gene expression in obesity being the result of impaired SNS activity. In the present study we used three models to assess the role of the SNS in regulating adipsin gene expression. First we exposed mice to the cold (4 degrees C), a potent activator of SNS activity. Second, we chemically sympathectomized mice with 60H-dopamine. Third, we treated mice with BRL 26830A, an atypical beta adrenoreceptor agonist. In contrast to our initial hypothesis, these studies demonstrate that alterations of SNS activity do not affect adipsin gene expression in normal mice. Neither increased SNS activity secondary to cold exposure nor decreased SNS activity resulting from sympathectomy alter serum adipsin concentration or adipsin mRNA levels in white (WAT) and brown adipose tissue (BAT). Surprisingly, treatment of lean mice with BRL 26830A decreases both adipsin serum concentrations and adipsin mRNA levels, suggesting a potential role for atypical beta adrenoreceptors in pathways that suppress adipsin expression in vivo. The significance of this observation with respect to adipocyte physiology is unclear at present. Future studies will be aimed at defining the molecular mechanisms by which BRL 26830A suppresses adipsin gene expression and the physiological significance of this effect.
 ...
PMID:Alterations in sympathetic nervous system activity do not regulate adipsin gene expression in mice. 164 81

Adipsin gene expression is greatly diminished in certain forms of genetic and acquired obesity. In the present study we evaluate the time course for the development of adipsin deficiency in obesity and its regulation by the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. Previously, it was unknown whether adipsin deficiency occurred before or after the development of massive obesity. In the first series of experiments in which mice were treated with monosodium glutamate (MSG) for the first week of life, we demonstrate that adipsin deficiency occurs early in the development of MSG-induced obesity as evidenced by decreased circulating adipsin concentrations by 1 week of age and deficient adipsin mRNA levels in white adipose tissue (WAT) by 2 weeks. In db/db mice, diminished circulating adipsin was noted at 2 weeks of age. In both models, decreased adipsin gene expression precedes the development of marked obesity. Little is known about the factors which regulate adipsin gene expression in obesity. Common to the ob/ob, db/db and MSG models is diminished thermogenesis and sympathetic nervous system activity. In a second series of experiments we sought to determine whether adipsin deficiency in obesity could be corrected by treatment with ephedrine and caffeine (E+C), a sympathomimetic-thermogenic mixture previously shown to increase thermogenesis and reverse obesity in some models. 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). In ob/ob mice, however, E+C treatment produced a negligible increase in adipsin mRNA levels in WAT and BAT as well as serum adipsin concentrations and this correlated with only a very small decrease in obesity. Thus, the ability of E+C to increase adipsin gene expression correlated with its ability to reverse obesity in these two models. Finally, the effect of E+C on adipsin gene expression may not be exerted directly on the fat cell since treatment of cultured 3T3-F442A adipocytes and isolated rat adipocytes in primary culture produced no effect on adipsin mRNA or secreted protein despite a lipolytic effect as measured by increased glycerol release. In summary, decreased adipsin gene expression occurs early in the development of MSG and db/db obesity and is markedly increased in the MSG model by the sympathomimetic-thermogenic drug mixture, E+C, which also reverses obesity. Elucidation of the factors responsible for these effects may enhance our understanding of fat cell gene regulation and obesity.
 ...
PMID:Reduced adipsin expression in murine obesity: effect of age and treatment with the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. 230 16