Cardiovascular response, feeding behavior and locomotor activity in mice lacking the NPY Y1 receptor

Abstract

Neuropeptide Y (NPY) is a 36-amino-acid neurotransmitter which is widely distributed throughout the central and peripheral nervous system. NPY involvement has been suggested in various physiological responses including cardiovascular homeostasis and the hypothalamic control of food intake. At least six subtypes of NPY receptors have been described. Because of the lack of selective antagonists, the specific role of each receptor subtype has been difficult to establish. Here we describe mice deficient for the expression of the Y1 receptor subtype. Homozygous mutant mice demonstrate a complete absence of blood pressure response to NPY, whereas they retain normal response to other vasoconstrictors. Daily food intake, as well as NPY-stimulated feeding, are only slightly diminished, whereas fast-induced refeeding is markedly reduced. Adult mice lacking the NPY Y1 receptor are characterized by increased body fat with no change in protein content. The higher energetic efficiency of mutant mice might result, in part, from the lower metabolic rate measured during the active period, associated with reduced locomotor activity. These results demonstrate the importance of NPY Y1 receptors in NPY-mediated cardiovascular response and in the regulation of body weight through central control of energy expenditure. In addition, these data are also indicative of a role for the Y1 receptor in the control of food intake.

To subjugate NPY is to improve the quality of life and live longer

“…Results from diverse molecular and genetic paradigms are consistent with the implication that NPY, in concert with co-expressed orexigenic AgrP, GABA and adrenergic transmitters, constitutes an obligatory orexigenic signaling modality that is intimately involved in propagation of the timely appetitive drive under the direction of photoperiodic and hormonal cues (7,11,(27)(28)(29)47,(49)(50)(51)54,(56)(57)(58)(59). Additional recent disclosures that the hard wiring for the timely operation of this interplay is established during postnatal development have put the notion that NPY is a physiological appetite transducer on firm footing (11,(28)(29)(30)49,64).…”

Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats

“…In keeping with this, body weight was not affected when haloperidol was administered orally to male rats for three or six weeks (Minet-Ringuet et al, 2005 andPouzet et al, 2003), and was even suppressed under the longer treatment period of 80 weeks (Yoshida et al, 1995). The early stages of obesity, indicated by an increase in percent body fat, have been observed even in the absence of increases in body weight or food intake (Kushi et al, 1998, Pedrazzini et al, 1998and Sainsbury et al, 1997. This is due to preferential channelling of fuels from lean tissues such as muscle and bone towards white This study examined the effects of chronic subcutaneous infusion of supratherapeutic doses of a typical (haloperidol) and an atypical (risperidone) antipsychotic drugs on endocrine functions and metabolic profile in male SpragueeDawley axes (testosterone), the two antipsycho on endocrine activities, with haloperido insulin levels and risperidone incre levels.…”

“…In k weight was not affected when halope orally to male rats for three or six et al., 2005;Pouzet et al, 2003), and w der the longer treatment period of 80 1995). The early stages of obesity, in in percent body fat, have been observ of increases in body weight or food 1998; Pedrazzini et al, 1998; Sainsbu due to preferential channelling of f such as muscle and bone towards wh the influence of hormonal changes su levels of insulin (Cusin et al, 1990laume-Gentil et al, 1993 and growt 1996) and reduced serum levels of t et al, 1966), IGF-1 (Shaw et al, 2 (Mudali and Dobs, 2004). However, only does chronic haloperidol admi have no effect on body weight or foo effect on adiposity or the serum leve mones that modulate body compositio (2,33) ¼ 3.296, p < 0.05; Fisher's peridol), pancreas (F(2,33) ¼ 7.051, , p < 0.01 vs. vehicle or haloperidol) 4, p < 0.05; Fisher's PLSD, p < 0.01 e risperidone-treated group (Table 1).…”

Body weight is regulated by the brain: a link between feeding and emotion

“…161 Moreover, Y1-R À/À mice display a markedly blunted feeding response to fasting. 159 Finally, the stomach-derived hormone, ghrelin, increases food intake and can directly act on Arc NPY neurons, 6,7,26,[162][163][164] supporting an important role of Arc NPY/AgRP neurons in feeding regulation. Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor.…”

“…For example, NPY À/À and Y1-R À/À mice are not hypophagic, [157][158][159][160] although this may be dependent on the background strain of the mouse studied. Nevertheless, other lines of evidence indicate that such discrepancies do not diminish the potential therapeutic efficacy of NPYergic agents.…”