Article
GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein.
Endocrine Research, Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana 46285, USA.
Endocrinology (impact factor:
4.46).
03/2002;
143(2):558-68.
Source: PubMed
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Citations (0)
- Cited In (9)
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Article: Mice with hyperghrelinemia are hyperphagic and glucose intolerant and have reduced leptin sensitivity.
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ABSTRACT: Ghrelin is the only known peripheral hormone to increase ingestive behavior. However, its role in the physiological regulation of energy homeostasis is unclear because deletion of ghrelin or its receptor does not alter food intake or body weight in mice fed a normal chow diet. We hypothesized that overexpression of ghrelin in its physiological tissues would increase food intake and body weight. We used bacterial artificial chromosome transgenesis to generate a mouse model with increased ghrelin expression and production in the stomach and brain. We investigated the effect of ghrelin overexpression on food intake and body weight. We also measured energy expenditure and determined glucose tolerance, glucose stimulated insulin release, and peripheral insulin sensitivity. Ghrelin transgenic (Tg) mice exhibited increased circulating bioactive ghrelin, which was associated with hyperphagia, increased energy expenditure, glucose intolerance, decreased glucose stimulated insulin secretion, and reduced leptin sensitivity. This is the first report of a Tg approach suggesting that ghrelin regulates appetite under normal feeding conditions and provides evidence that ghrelin plays a fundamental role in regulating beta-cell function.Diabetes 02/2009; 58(4):840-6. · 8.29 Impact Factor -
Article: Anatomy and regulation of the central melanocortin system.
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ABSTRACT: The central melanocortin system is perhaps the best-characterized neuronal pathway involved in the regulation of energy homeostasis. This collection of circuits is unique in having the capability of sensing signals from a staggering array of hormones, nutrients and afferent neural inputs. It is likely to be involved in integrating long-term adipostatic signals from leptin and insulin, primarily received by the hypothalamus, with acute signals regulating hunger and satiety, primarily received by the brainstem. The system is also unique from a regulatory point of view in that it is composed of fibers expressing both agonists and antagonists of melanocortin receptors. Given that the central melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.Nature Neuroscience 06/2005; 8(5):571-8. · 15.53 Impact Factor -
Article: BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage.
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ABSTRACT: Obesity is accompanied by an increase in both adipocyte number and size. The increase in adipocyte number is the result of recruitment to the adipocyte lineage of pluripotent stem cells present in the vascular stroma of adipose tissue. These pluripotent cells have the potential to undergo commitment and then differentiate into adipocytes, as well as myocytes, osteocytes, and chondrocytes. In this article, we show that both bone morphogenetic protein (BMP)2 and BMP4 can induce commitment of C3H10T1/2 pluripotent stem cells into adipocytes. After treatment of C3H10T1/2 stem cells with these BMPs during proliferation followed by exposure to differentiation inducers at growth arrest, nearly all cells enter the adipose development pathway, express specific adipocyte markers, and acquire the adipocyte phenotype. Overexpression of constitutively active BMP receptor (CA)-BMPr1A or CA-BMPr1B induces commitment in the absence of BMP2/4, whereas overexpression of a dominant-negative receptor dominant-negative-BMPr1A suppresses commitment induced by BMP. Also, knockdown of the expression of Smad4 (coregulator in the BMP/Smad signaling pathway) with RNAi disrupts commitment by the BMPs. However, knockdown of expression of p38 MAPK (an intermediary in the BMP/MAPK signaling pathway) with RNAi had little effect on BMP-induced commitment. Together, these findings indicate that the BMP/Smad signaling pathway has a dominant role in adipocyte lineage determination. Proteomic analysis identified lysyl oxidase (LOX), a bona fide downstream target gene of the BMP signaling pathway. Expression of LOX is induced by BMP2/4 during adipocyte lineage commitment, and knockdown of its expression disrupts the commitment process.Proceedings of the National Academy of Sciences 08/2009; 106(31):12670-5. · 9.68 Impact Factor
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Keywords
AGRP action
AIDS wasting
bone mass
chronic peripheral treatment
endogenous GH secretagogue
fat mass
ghrelin receptor agonist induced
GHRP-2 treatment
GHRP-induced weight gain
Hypothalamic mRNA levels
hypothalamic NPY neurons
lean mass
melanocortin-receptor agonist MT-II
NPY-deficient [Npy(-/-)
orexigenic melanocortin receptor antagonist
positive energy balance
sc injections
stimulating adiposity
synthetic ghrelin receptor agonist
treatment option
