Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?

Dryden, Simon; Frankish, Helen; Wang, Qiong; Williams, Gareth

doi:10.1111/j.1365-2362.1994.tb01089.x

Cited by 123 publications

(77 citation statements)

References 149 publications

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“…NPY is an important regulator of food intake and energy metabolism, with orexigenic activity. 42 Enhanced levels of NPY and of NPY mRNA expression have been described in the hypothalamus of obese rodents. 43 We found higher NPY expression in the hypothalamus of control and leptin-treated animals under HF diet, which is suggestive of both leptin and insulin resistance, and could be partially responsible for the overfeeding of rats under this diet.…”

Section: Discussionmentioning

confidence: 99%

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

et al. 2007

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Ciber Fisiopatología obesidad y nutrición (CB06/03) Instituto Salud Carlos III, SpainBackground: There is epidemiological evidence that perinatal nutritional factors may have long-term effects on obesity. Which nutrients or food components are involved in this programming mechanism are unknown. Breast milk contains leptin, a hormone that regulates food intake and energy expenditure, and previous studies in rats have shown that leptin orally administered during lactation exerts anorexigenic effects. Objective: To evaluate whether supplementation with physiological doses of oral leptin during lactation has long-term effects on body weight regulation. Design: A daily oral dose of leptin (equivalent to five times the amount of leptin ingested normally from maternal milk during the suckling period) or the vehicle was given to suckling male rats during lactation. Animals were fed after weaning with a normal fat (NF) or a high-fat (HF) diet. We followed body weight and food intake of animals until the age of 6 months, and measured the size of adipose tissue depots, the thermogenic capacity, the expression of leptin in the stomach and adipose tissues and the expression of two appetite-related peptides (neuropeptide Y (NPY) and proopiomelanocortin (POMC)), leptin receptor (OB-Rb) and suppressor of cytokine signalling 3 (SOCS-3) in the hypothalamus at the age of 6 months. Results: Leptin-treated animals had, in adulthood, lower body weight and fat content and ate fewer calories than their untreated controls. Unlike adipocitary leptin production, adult animals that were leptin-treated during lactation displayed higher gastric leptin production without changes in OB-Rb mRNA levels. In addition, in response to HF diet, leptin-treated animals (contrary to controls) showed lower hypothalamic NPY/POMC mRNA ratio. Hypothalamic OB-Rb mRNA levels decreased in control animals as an effect of HF diet feeding, but remained unchanged in leptin-treated animals; SOCS-3 mRNA levels were lower in leptin-treated animals than in their controls, both under normal or HF diet. Conclusion: The animals that received leptin during lactation become more protected against fat accumulation in adult life and seem to be more sensitive to the short-and long-term regulation of food intake by leptin. Thus, leptin plays an important role in the earlier stages of neonatal life, as a component of breast milk, in the prevention of later obesity.

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Section: Discussionmentioning

confidence: 99%

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

et al. 2007

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“…Under these conditions, plasma leptin levels fall in parallel with the decline in body fat mass, and the enhanced NPY neuronal activity may be due to loss of inhibition by leptin. Concomitant falls in insulin, which also inhibits ARC NPY neuronal activity (Schwartz et al 1992;Dryden et al 1994), may also contribute.…”

Section: Neuropeptide Y and Energy Homeostasismentioning

confidence: 99%

“…In these circumstances several groups have reported increased NPY expression, raised NPY peptide levels in the ARC and PVN in particular, and elevated NPY secretion in the PVN (measured directly in conscious animals using the stereotactic 'push-pull' sampling technique; Dryden et al 1994Dryden et al , 2000. These states include food restriction and fasting, insulin-deficient diabetes and lactation, especially when mild food restriction is superimposed (Smith, 1993;Pickavance et al 1996;Dryden et al 2000).…”

Section: Neuropeptide Y and Energy Homeostasismentioning

confidence: 99%

“…The ARC NPY neurones are strategically situated to integrate a variety of nutritional and neural signals, and to interact with and influence other neuronal systems (Dryden et al 1994). A subpopulation of the ARC NPY neurones expresses the 'long' isoform of the leptin receptor (known as OBRb; the fully functional form with intact intracellular signalling domains) and these cells appear to respond specifically under conditions in which circulating leptin levels are altered (Baskin et al 1999).…”

Section: Neuropeptide Ymentioning

confidence: 99%

“…The NPY neurones are therefore potential hypothalamic targets for leptin, and inhibition of the synthesis (and presumably release) of the powerfully orexigenic NPY seems likely to explain, at least partly, the ability of leptin to induce hypophagia and weight loss. Insulin has the same central actions as leptin on energy balance and, before the discovery of leptin, was attributed an important role as a signal that reflects fat mass (Schwartz et al 1992;Dryden et al 1994). Insulin receptors are expressed in the mediobasal hypothalamus, and especially the median eminence, and insulin has been shown to inhibit NPY synthesis and its secretion in the PVN; however, it is not clear whether insulin receptors are actually carried by the NPY neurones or by neurones that impinge on them (Schwartz et al 1992;Dryden et al 2000).…”

Section: Neuropeptide Ymentioning

confidence: 99%

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The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box

2000

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The hypothalamus is the focus of many peripheral signals and neural pathways that control energy homeostasis and body weight. Emphasis has moved away from anatomical concepts of ‘feeding’ and ‘satiety’ centres to the specific neurotransmitters that modulate feeding behaviour and energy expenditure. We have chosen three examples to illustrate the physiological roles of hypothalamic neurotransmitters and their potential as targets for the development of new drugs to treat obesity and other nutritional disorders. Neuropeptide Y (NPY) is expressed by neurones of the hypothalamic arcuate nucleus (ARC) that project to important appetite-regulating nuclei, including the paraventricular nucleus (PVN). NPY injected into the PVN is the most potent central appetite stimulant known, and also inhibits thermogenesis; repeated administration rapidly induces obesity. The ARC NPY neurones are stimulated by starvation, probably mediated by falls in circulating leptin and insulin (which both inhibit these neurones), and contribute to the increased hunger in this and other conditions of energy deficit. They therefore act homeostatically to correct negative energy balance. ARC NPY neurones also mediate hyperphagia and obesity in the ob/ob and db/db mice and fa/fa rat, in which leptin inhibition is lost through mutations affecting leptin or its receptor. Antagonists of the Y5 receptor (currently thought to be the NPY ‘feeding’ receptor) have anti-obesity effects. Melanocortin-4 receptors (MC4-R) are expressed in various hypothalamic regions, including the ventromedial nucleus and ARC. Activation of MC4-R by agonists such as α-melanocyte-stimulating hormone (a cleavage product of pro-opiomelanocortin which is expressed in ARC neurones) inhibits feeding and causes weight loss. Conversely, MC4-R antagonists such as ‘agouti’ protein and agouti gene-related peptide (AGRP) stimulate feeding and cause obesity. Ectopic expression of agouti in the hypothalamus leads to obesity in the AVY mouse, while AGRP is co-expressed by NPY neurones in the ARC. Synthetic MC4-R agonists may ultimately find use as anti-obesity drugs in human subjects Orexins-A and -B, derived from prepro-orexin, are expressed in specific neurones of the lateral hypothalamic area (LHA). Orexin-A injected centrally stimulates eating and prepro-orexin mRNA is up regulated by fasting and hypoglycaemia. The LHA is important in receiving sensory signals from the gut and liver, and in sensing glucose, and orexin neurones may be involved in stimulating feeding in response to falls in plasma glucose.

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Effects of medroxyprogesterone acetate on food intake, body composition, and resting energy expenditure in patients with advanced, nonhormone-sensitive cancer

Simons¹,

Schols²,

Hoefnagels

et al. 1998

Cancer

100

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Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?

Cited by 123 publications

References 149 publications

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box

Effects of medroxyprogesterone acetate on food intake, body composition, and resting energy expenditure in patients with advanced, nonhormone-sensitive cancer

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