Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mutant gene responsible for obesity in the ob/ob mouse was recently identified by positional cloning (Zhang Y., R. Proenca, M. Maffel, M. Barone, L. Leopold, and J.M. Friedman. 1994. Nature (Lond.) 372:425). The encoded protein and to represent and "adipostat" signal reflecting the state of energy stores. We confirm that the adipocyte is the source of ob mRNA and that the predicted 16-kD ob protein is present in rodent serum as detected by Western blot. To evaluate the hypothesis that it might represent an adipostat, we assessed serum levels of ob protein and expression of ob mRNA in adipose cells and tissue of rodents in response to a variety of perturbations which effect body fat mass. Both ob protein and ob mRNA expression are markedly increased in obesity. The levels of ob protein are approximately 5-10-fold elevated in serum of db/db mice, in mice with hypothalamic lesions caused by neonatal administration of monosodium glutamate (MSG), and in mice with toxigene induced brown fat ablation, (UCP-DTA). Very parallel changes are observed in adipocyte ob mRNA expression in these models and in ob/ob mice. As predicted however, no serum ob protein could be detected in the ob/ob mice. By contrast to obesity, starvation of normal rats and mice for 1-3 d markedly suppresses ob mRNA abundance, and this is reversed with refeeding. Similarly, ob protein concentration in normal mice falls to undetectable levels with starvation. In the ob/ob, UCP-DTA and MSG models, overexpression of ob mRNA is reversed by caloric restriction. These data support the hypothesis that expression of ob mRNA and protein are regulated as a function of energy stores, and that ob serves as a circulating feedback signal to sites involved in regulation of energy homeostasis.
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PMID:Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. 765 36

Melanin concentrating hormone (MCH) and the orexins (A and B) have been identified as neuropeptides localized to the lateral hypothalamic area (LHA) and are potential regulators of energy homeostasis. Potential factors regulating expression of both MCH and the orexins include fasting and leptin. Previous studies have generated conflicting data and, as there is little leptin receptor expressed in the lateral hypothalamus, it is likely that any observed leptin effects on these peptides are indirect. In this study, we examined MCH and preproorexin expression in mice in physiological states of starvation, with or without leptin administration, in addition to characterizing MCH and preproorexin expression in well-known obesity models, including ob/ob and UCP-DTA mice. Neuropeptide Y (NPY) expression in the arcuate nucleus was used as a positive control. After a 60-h fast, expression of both NPY and MCH mRNA was increased (by 148 and 33%, respectively) while preproorexin expression in the murine LHA did not change. Leptin administration to fasted mice blunted the rise in MCH and NPY expression towards control levels. In contrast, there was a 78% increase in preproorexin expression in fasted mice in response to peripheral leptin administration. MCH expression was increased (by 116%) in ob/ob mice at baseline, as we have previously reported. In addition, leptin treatment of ob/ob mice blunted the increase in MCH expression. In contrast, preproorexin expression did not differ in the leptin-deficient ob/ob mice or in the obese hyperleptinemic brown adipose tissue deficient (UCP-DTA) mice in comparison with controls. In summary, MCH expression is increased in two states of decreased leptin, fasting and ob/ob mice, and leptin replacement blunts MCH expression in both paradigms. Thus, MCH expression appears to be regulated by leptin. In contrast, preproorexin expression does not respond acutely to fasting, although it is acutely increased by leptin treatment during fasting. These preproorexin responses are in contrast to those seen with well-characterized orexigenic neuropeptides, such as NPY and AgRP, suggesting that appetite regulation may not be a significant physiological role of orexins. This conclusion is further supported by the observation that orexin ablated mice have arousal and not feeding deficits.
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PMID:Characterization of melanin concentrating hormone and preproorexin expression in the murine hypothalamus. 1125 73