Thermoregulatory effect of intracerebral injections of neuropeptide Y in rats at different environmental temperatures

Szreder, Z.; Hori, Tetsuro; Kaizuka, Yasuo

doi:10.1016/0306-3623(94)90014-0

Cited by 22 publications

(13 citation statements)

References 27 publications

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“…NPY-infused rats exhibited two-to threefold increases over controls in basal plasma insulin levels over the infusion period. This hyperinsulinemia, in addition to reduced thermogenesis (9,(42)(43)(44)(45), is the likely primary mechanism by which NPY-infused rats become obese in the absence of hyperphagia. In contrast to the NPY-infused group, rats that received HS014 infusions did not exhibit any significant change in insulinemia relative to control rats, indicating that hyperinsulinemia may not be the only …”

Section: Discussionmentioning

confidence: 99%

“…It is well established that central NPY administration decreases sympathetically mediated thermogenic activity in BAT (9,(42)(43)(44)(45), most likely by decreasing the expression of UCP-1 (9). This effect is likely to contribute to NPYinduced obesity because BAT ablation per se also results in an obesity syndrome (46).…”

Section: Mc4 Antagonist-versus Npy-induced Obesitymentioning

confidence: 99%

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Chronic Central Melanocortin-4 Receptor Antagonism and Central Neuropeptide-Y Infusion in Rats Produce Increased Adiposity by Divergent Pathways

et al. 2002

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Increased hypothalamic neuropeptide-Y (NPY) action and disruption of the melanocortin (MC)-4 receptor both result in hyperphagia and obesity. To determine whether similar hormonal and metabolic mechanisms are involved in these two obesity syndromes, we investigated the time course of effects induced by 6-day intracerebroventricular (ICV) infusion of NPY (3.5 nmol/day) or the MC4 receptor antagonist HS014 (4.8 nmol/day) in rats pair-fed with vehicle-infused controls. The weight of white adipose tissue (WAT) deposits was increased after 6-day NPY and HS014 infusion compared with controls, and the increase was significantly greater in HS014-than in NPY-infused rats (retroperitoneal WAT: NPY 0.57 ؎ 0.05; HS014 0.80 ؎ 0.05; control 0.43 ؎ 0.03% body wt, n ‫؍‬ 8 -13, P < 0.05). Plasma leptin was also increased in both experimental groups (NPY 10.6 ؎ 1.9; HS014 4.4 ؎ 0.9; control 2.0 ؎ 0.1 ng/ml, n ‫؍‬ 8 -13, P < 0.05 for all comparisons). Basal plasma corticosterone and insulin levels were increased by ICV NPY infusion, whereas HS014-infused rats showed no significant increase in these parameters on any of 1-6 days of infusion. Both NPY and HS014 infusion potentiated intravenous glucose-induced (300 mg/kg) plasma insulin levels, and there was no difference in glycemia among groups. In NPY-infused rats, the plasma free fatty acid levels were decreased and triglyceridemia was increased compared with controls, but these parameters were unchanged in HS014-infused rats. Hepatic triglyceride content was significantly increased by HS014 but not by NPY infusion. Levels of uncoupling protein-1 mRNA in brown adipose tissue were significantly decreased after 6 days of HS014 infusion, similar to the effect of central NPY. Because ICV HS014 induced at least as great an increase in fat mass as ICV NPY and yet had divergent hormonal and metabolic effects, we conclude that MC4 receptor antagonism does not induce obesity solely by regulation of the endogenous NPY-ergic system. Diabetes 51:152-158, 2002 N europeptide-Y (NPY) is a highly potent orexigenic peptide synthesized in the brain (1). Genetically obese ob/ob and db/db mice and fa/fa rats exhibit a lack of leptin function as their primary defect (2-5), and all exhibit increased NPY expression and secretion in the hypothalamus (6) caused by a lack of leptin's known inhibitory effect on NPY-ergic activity (7). Although other peptides are likely to be involved (1), this increase in hypothalamic NPY probably contributes to obesity in ob/ob, db/db, and fa/fa rodents because intracerebroventricular (ICV) infusions of NPY in normal rodents produce effects similar to those seen in the genetically obese rodent models. These include increased food intake, body weight, fat accumulation, plasma insulin, leptin, and corticosterone concentrations, decreased brown adipose tissue (BAT) thermogenesis, and inhibition of the somatotropic and gonadotropic axes (8 -12).Several dominant mutations at the agouti locus in the mouse also cause a syndrome of marked obesity, hyperinsulinemia, insulin resist...

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Section: Discussionmentioning

confidence: 99%

Section: Mc4 Antagonist-versus Npy-induced Obesitymentioning

confidence: 99%

Chronic Central Melanocortin-4 Receptor Antagonism and Central Neuropeptide-Y Infusion in Rats Produce Increased Adiposity by Divergent Pathways

et al. 2002

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“…Notably, the orexigenic peptides NPY or AgRP (or MC4 receptor antagonism) not only increase food intake but also reduce parameters related to energy expenditure. Intracerebroventricular or intrahypothalamic NPY administration decreases core temperature (Szreder et al, 1994 andCurrie andCoscina, 1995) and reduces oxygen consumption (Hwa et al, 1999). Central NPY administration decreases sympathetically mediated thermogenic activity in brown adipose tissue (Kotz et al, 1998 andEgawa et al, 1991), most likely by decreasing the expression of uncoupling protein-1 (Kotz et al, 1998).…”

Section: Effects Of Hypothalamic Regulators Of Energy Balance On Enermentioning

confidence: 99%

Role of the arcuate nucleus of the hypothalamus in regulation of body weight during energy deficit

Sainsbury

Zhang

2010

Molecular and Cellular Endocrinology

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Acute or long-term energy deficit in lean or obese rodents or humans stimulates food intake or appetite and reduces metabolic rate or energy expenditure. These changes contribute to weight regain in post-obese animals and humans. Some studies show that the reduction in metabolic rate with energy deficit in overweight people is transient. Energy restriction has been shown in some but not all studies to reduce physical activity, and this may represent an additional energy-conserving adaptation. Energy restriction up-regulates expression of the orexigenic neuropeptide Y, agouti related peptide and opioids and down-regulates that of the anorexigenic alpha-melanocyte stimulating hormone or its precursor pro-opioomelanocortin and the co-expressed cocaine and amphetamine-regulated transcript in the arcuate nucleus of the hypothalamus. Recapitulating these hypothalamic changes in sated animals mimics the effects of energy deficit, namely increased food intake, reduced physical activity and reduced metabolic rate, suggesting that these energy-conserving adaptations are at least partially mediated by the hypothalamus.

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“…Increased central NPY-ergic tone elicits robust hyperphagia and induces a series of obesogenic changes that lead to gain of body weight and fat. [1][2][3][4][5][6] These obesefying changes include decreases in body temperature and thermogenetic capacity in brown adipose tissue 5,[7][8][9][10] Findicative of decreased energy expenditure, glucose partitioning towards storage rather than utilization, 2,11 increased lipogenic activity in white adipose tissue and liver, 7,8,12 and increased respiratory exchange ratio (RER) [13][14][15] Findicative of a higher preference for carbohydrate versus lipid as a fuel source. Importantly, when NPY-induced hyperphagia is prevented by pair feeding, central administration of NPY for 5-7 days in rodents still leads to significant fat gain without changes in body weight, 2,12 showing an important function of NPY in increasing adiposity independent of changes in food intake and body weight.…”

Section: Introductionmentioning

confidence: 99%

Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion

et al. 2009

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Objective: Neuropeptide Y and its Y receptors are important players in the regulation of energy homeostasis. However, while their functions in feeding regulation are well recognized, functions in other critical aspects of energy homeostasis are largely unknown. To investigate the function of Y1 receptors in the regulation of energy homeostasis, we examined energy expenditure, physical activity, body composition, oxidative fuel selection and mitochondrial oxidative capacity in germline Y1 À/À mice as well as in a conditional Y1-receptor-knockdown model in which Y1 receptors were knocked down in peripheral tissues of adult mice. Results: Germline Y1À/À mice of both genders not only exhibit a decreased respiratory exchange ratio, indicative of increased lipid oxidation, but interestingly also develop late-onset obesity. However, the increased lipid oxidation is a primary effect of Y1 deletion rather than secondary to increased adiposity, as young Y1 À/À mice are lean and show the same effect. The mechanism behind this is likely because of increased liver and muscle protein levels of carnitine palmitoyltransferase-1 (CPT-1) and maximal activity of key enzymes involved in b-oxidation; b-hydroxyacyl CoA dehydrogenase (bHAD) and medium-chain acyl-CoA dehydrogenase (MCAD), leading to increased mitochondrial capacity for fatty acid transport and oxidation. These effects are controlled by peripheral Y1-receptor signalling, as adult-onset conditional Y1 knockdown in peripheral tissues also leads to increased lipid oxidation, liver CPT-1 levels and bHAD activity. Importantly, these mice are resistant to diet-induced obesity. Conclusions: This work shows the primary function of peripheral Y1 receptors in the regulation of oxidative fuel selection and adiposity, opening up new avenues for anti-obesity treatments by targeting energy utilization in peripheral tissues rather than suppressing appetite by central effects.

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Thermoregulatory effect of intracerebral injections of neuropeptide Y in rats at different environmental temperatures

Cited by 22 publications

References 27 publications

Chronic Central Melanocortin-4 Receptor Antagonism and Central Neuropeptide-Y Infusion in Rats Produce Increased Adiposity by Divergent Pathways

Chronic Central Melanocortin-4 Receptor Antagonism and Central Neuropeptide-Y Infusion in Rats Produce Increased Adiposity by Divergent Pathways

Role of the arcuate nucleus of the hypothalamus in regulation of body weight during energy deficit

Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion

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