Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice.

Cachexia, defined as an involuntary weight loss ≥ 5%, is a serious and dose-limiting side effect of chemotherapy that decreases survival in cancer patients. Alterations in lipid metabolism are thought to cause the lipodystrophy commonly associated with cachexia. Ghrelin has been proposed to ameliorate the alterations in lipid metabolism due to its orexigenic and anabolic properties.

Central and peripheral roles of ghrelin on glucose homeostasis.

Ghrelin, an acylated 28-amino-acid peptide, is an endogenous ligand of the growth hormone secretagogue type 1a (GHS-R1a). Ghrelin is best known for its hypothalamic actions on growth hormone-releasing hormone neurons and neuropeptide Y/agouti-related peptide neurons; however, ghrelin affects multiple organ systems and the complexity of its functions is only now being realized. Although ghrelin is mainly produced in the stomach, it is also produced in low levels by the hypothalamus and by most peripheral tissues.

Studies of cocaine- and amphetamine-regulated transcript (CART) knockout mice.

CART (cocaine- and amphetamine-regulated transcript) peptides are neuropeptides expressed throughout the central nervous system and have been implicated in a variety of physiological processes. Research on the many physiological processes involving CART peptide have been somewhat limited by the lack of an identified CART antagonist. Development of CART peptide deficient mice has allowed scientists to further explore the many functions of CART peptide.

Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice.

Ghrelin and leptin are suggested to regulate energy homeostasis as mutual antagonists on hypothalamic neurons that regulate feeding behavior. We employed reverse genetics to investigate the interplay between ghrelin and leptin. Leptin-deficient mice (ob/ob) are hyperphagic, obese, and hyperglycemic.

Growth hormone secretagogues: prospects and potential pitfalls.

The growth hormone secretagogues (GHSs) are the first well-characterised agents that rejuvenate the growth hormone (GH)/insulin-like growth factor (IGF-1) axis. This property was discovered during investigations of the underlying causative mechanisms of age-related endocrine changes. Chronic administration of the long acting GHS, MK-0677, reverses the age-related decline in pulse-amplitude of GH secretion and restores IGF-1 levels producing profiles typical of young adults.

Vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating peptide receptor 2 deficiency in mice results in growth retardation and increased basal metabolic rate.

Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are two closely related peptides that bind two homologous G protein-coupled receptors, VIP/PACAP receptor 1 (VPAC1R) and VIP/PACAP receptor II (VPAC2R), with equally high affinity. Recent reports suggest that VPAC2R plays a role in circadian rhythm and T cell functions. To further elucidate the functional activities of VPAC2R, we generated VPAC2R-deficient mice by deleting exons VIII-X of the VPAC2R gene.

Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity.

The hypothalamic neuropeptide melanin-concentrating hormone (MCH) has been implicated in a variety of physiological functions including the regulation of feeding and energy homeostasis. Two MCH receptors (MCHR1 and MCHR2) have been identified so far. To decipher the functional role of the MCH receptors, we have generated and phenotypically characterized mice rendered deficient in MCHR1 expression by homologous recombination.