The role of neuropeptide Y in the antiobesity action of the obese gene product

Stephens, T.; Basinski, Margret B.; Bristow, Pamela K.; Bue-Valleskey, Juliana M.; Burgett, Stanley G.; Craft, Libbey; Hale, John E.; Hoffmann, J. A.; Hsiung, Hansen M.; Kriauciunas, Aidas; MacKellar, W.C.; Rosteck, Paul R.; Schoner, Brigitte E.; Smith, Dennis P.; Tinsley, Frank C.; Zhang, Xingyue; Heiman, Mark L.

doi:10.1038/377530a0

Cited by 1,439 publications

(924 citation statements)

References 11 publications

Supporting

Mentioning

849

Contrasting

Unclassified

Order By: Relevance

“…[34][35][36] Although leptin resistance was reported in obesity, 37 reduced Arc NPY content in our mice at 10 weeks may represent a possible response to the hyperleptinemia. The decreased NPY concentrations in the AH and PH may reflect a decrease in NPY release from the Arc.…”

Section: Npy Cck and Adipokines In Dietary Obesity Mj Morris Et Almentioning

confidence: 62%

See 1 more Smart Citation

Brain neuropeptide Y and CCK and peripheral adipokine receptors: temporal response in obesity induced by palatable diet

et al. 2007

View full text Add to dashboard Cite

Objective: Palatable food disrupts normal appetite regulation, which may contribute to the etiology of obesity. Neuropeptide Y (NPY) and cholecystokinin play critical roles in the regulation of food intake and energy homeostasis, while adiponectin and carnitine palmitoyltransferase (CPT) are important for insulin sensitivity and fatty acid oxidation. This study examined the impact of short-and long-term consumption of palatable high-fat diet (HFD) on these critical metabolic regulators. Methods: Male C57BL/6 mice were exposed to laboratory chow (12% fat), or cafeteria-style palatable HFD (32% fat) for 2 or 10 weeks. Body weight and food intake were monitored throughout. Plasma leptin, hypothalamic NPY and cholecystokinin, and mRNA expression of leptin, adiponectin, their receptors and CPT-1, in fat and muscles were measured. Results: Caloric intake of the palatable HFD group was 2-3 times greater than control, resulting in a 37% higher body weight. Fat mass was already increased at 2 weeks; plasma leptin concentrations were 2.4 and 9 times higher than control at 2 and 10 weeks, respectively. Plasma adiponectin was increased at 10 weeks. Muscle adiponectin receptor 1 was increased at 2 weeks, while CPT-1 mRNA was markedly upregulated by HFD at both time points. Hypothalamic NPY and cholecystokinin content were significantly decreased at 10 weeks. Conclusion: Palatable HFD induced hyperphagia, fat accumulation, increased adiponectin, leptin and muscle fatty acid oxidation, and reduced hypothalamic NPY and cholecystokinin. Our data suggest that the adaptive changes in hypothalamic NPY and muscle fatty acid oxidation are insufficient to reverse the progress of obesity and metabolic consequences induced by a palatable HFD.

show abstract

Section: Npy Cck and Adipokines In Dietary Obesity Mj Morris Et Almentioning

confidence: 62%

“…35,40 Fasting or chronic food restriction increases NPY mRNA expression, and re-feeding restores it. Both increases and decreases in brain NPY have been observed in previous short-and long-term studies using pelleted HFD.…”

Section: Npy Cck and Adipokines In Dietary Obesity Mj Morris Et Almentioning

confidence: 99%

Brain neuropeptide Y and CCK and peripheral adipokine receptors: temporal response in obesity induced by palatable diet

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Studies on mouse models with mutations in the leptin gene (ob/ob) or the leptin receptor gene (db/db) have provided valuable information on the relationship between leptin and the HPA axis. Hypercorticosteronemia was observed in both ob/ob and db/db mice [42][43][44]. Chronic leptin administration can reverse the hypercorticosteronemia in ob/ob mice prior to significant weight loss [44], suggesting a role of leptin in HPA function independent of its effects on energy homeostasis.…”

Section: Impact Of Leptin On Hpamentioning

confidence: 98%

The leptin hypothesis of depression: a potential link between mood disorders and obesity?

Lü

2007

Current Opinion in Pharmacology

259

198

View full text Add to dashboard Cite

SummaryThe adipose-derived hormone leptin is well known for its function in the control of energy homeostasis. Recent studies suggest a novel role for this adipokine in the regulation of mood and emotion. Low levels of leptin have been found to be associated with depressive behaviors in rodents and humans. Pharmacological studies indicate that leptin has antidepressant-like efficacy. Both leptin insufficiency and leptin resistance may contribute to alterations of affective status. Identifying the key brain regions that mediate leptin's antidepressant activity and dissecting its intracellular signal transduction pathways may provide new insights into the pathogenesis of depression and facilitate the development of novel therapeutic strategies for the treatment of this illness.

show abstract

“…Of all of these peptides however, NPY is one of the few which actually leads to the development of true obesity and insulin resistance when hypothalamic levels remain chronically elevated [3,28,30,33,40,46,47], as has been reported for various rodent genetic obesity syndromes [2,8,35,42]. The obesity syndrome which results from chronically elevated hypothalamic NPY levels in rodents [3,28,30,33,40,46,47] is still present even when NPY--induced hyperphagia is prevented [3,30,46], demonstrating that hyperphagia is not necessary for central NPY to produce its obesity--like effects.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of central neuropeptide Y on the somatotropic and gonadotropic axes in male rats are independent of adrenal hormones

Sainsbury

Herzog

2001

Peptides

View full text Add to dashboard Cite

Neuropeptide Y (NPY) in the hypothalamus exerts multiple physiological functions including stimulation of adipogenic pathways such as feeding and insulin secretion as well as inhibition of the somatotropic and gonadotropic axes. Since hypothalamic NPY--ergic activity is increased by negative energy balance, NPY enables coordinated regulation of growth and reproduction in parallel with energy availability. Chronic pathological increases in central NPY--ergic activity contribute to obesity. Many of the adipogenic effects of NPY are specifically dependent on adrenal glucocorticoids. However, in the current study we show that central NPY does not require adrenal hormones to inhibit the somatotropic and gonadotropic axes in rats. Male adrenalectomized and sham--operated normal rats were intracerebroventricularly (ICV) infused with NPY (15 µg/day) or saline for 5-7 days, and plasma leptin, insulin--like growth factor (IGF--1) and testosterone were assayed, and epididymal white adipose tissue (WATe) was weighed. In normal intact rats, WATe weight and leptinemia were significantly increased by NPY, and these effects were prevented by adrenalectomy. In normal rats, NPY markedly reduced plasma IGF--1 levels (470 ± 40 versus 1260 ± 90 ng/ml) and testosterone (0.53 ± 0.28 versus 5.4 ± 0.80 nmol/l in saline--infused controls, p < 0.0001). Adrenalectomy decreased plasma IGF--1 concentrations to 290 ± 30 ( p < 0.0001 versus normal rats), which were significantly reduced further by NPY. However, adrenalectomy had no significant effect on basal nor on NPY--induced plasma testosterone concentrations. In conclusion unlike the stimulatory effects of NPY on fat mass and leptinemia, NPY--induced inhibition of the somatotropic and gonadotropic axes in male rats do not require adrenal hormones.

show abstract

The role of neuropeptide Y in the antiobesity action of the obese gene product

Cited by 1,439 publications

References 11 publications

Brain neuropeptide Y and CCK and peripheral adipokine receptors: temporal response in obesity induced by palatable diet

Brain neuropeptide Y and CCK and peripheral adipokine receptors: temporal response in obesity induced by palatable diet

The leptin hypothesis of depression: a potential link between mood disorders and obesity?

Inhibitory effects of central neuropeptide Y on the somatotropic and gonadotropic axes in male rats are independent of adrenal hormones

Contact Info

Product

Resources

About