Neuropeptide Y in the Amygdala Induces Long-Term Resilience to Stress-Induced Reductions in Social Responses But Not Hypothalamic-Adrenal-Pituitary Axis Activity or Hyperthermia

Neuropeptide Y (NPY) is one the most potent orexigenic peptides found in the brain. It stimulates food intake with a preferential effect on carbohydrate intake. It decreases latency to eat, increases motivation to eat and delays satiety by augmenting meal size. The effects on feeding are mediated through at least two receptors, the Y1 and Y5 receptors. The NPY system for feeding regulation is mostly located in the hypothalamus. It is formed of the arcuate nucleus (ARC), where the peptide is synthesized, and the paraventricular (PVN), dorsomedial (DMN) and ventromedial (VMN) nuclei and perifornical area where it is active. This activity is modulated by the hindbrain and limbic structures. It is dependent on energy availability, e.g. upregulation with food deprivation or restriction, and return to baseline with refeeding. It is also sensitive to diet composition with variable effects of carbohydrates and fats. Leptin signalling and glucose sensing which are directly linked to diet type are the most important factors involved in its regulation. Absence of leptin signalling in obesity models due to gene mutation either at the receptor level, as in the Zucker rat, the Koletsky rat or the db / db mouse, or at the peptide level, as in ob / ob mouse, is associated with increased mRNA abundance, peptide content and/or release in the ARC or PVN. Other genetic obesity models, such as the Otsuka–Long–Evans–Tokushima Fatty rat, the agouti mouse or the tubby mouse, are characterized by a diminution in NPY expression in the ARC nucleus and by a significant increase in the DMN. Further studies are necessary to determine the exact role of NPY in these latter models. Long-term exposure to high-fat or high-energy palatable diets leads to the development of adiposity and is associated with a decrease in hypothalamic NPY content or expression, consistent with the existence of a counter-regulatory mechanism to diminish energy intake and limit obesity development. On the other hand, an overactive NPY system (increased mRNA expression in the ARC associated with an upregulation of the receptors) is characteristic of rats or rodent strains sensitive to dietary-induced obesity. Finally, NPY appears to play an important role in body weight and feeding regulation, and while it does not constitute the only target for drug treatment of obesity, it may nevertheless provide a useful target in conjunction with others.

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Review for "Long term effects of stress on hippocampal function: Emphasis on early life stress paradigms and potential involvement of neuropeptide Y"

10.1002/jnr.24614/v1/review2 ◽

2019 ◽

Author(s):

Bruce S. McEwen

Keyword(s):

Neuropeptide Y ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Hippocampal Function ◽

Long Term Effects ◽

Effects Of Stress

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Review for "Long term effects of stress on hippocampal function: Emphasis on early life stress paradigms and potential involvement of neuropeptide Y"

10.1002/jnr.24614/v1/review1 ◽

2019 ◽

Author(s):

Teresa Milner

Keyword(s):

Neuropeptide Y ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Hippocampal Function ◽

Long Term Effects ◽

Effects Of Stress

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Long-term depression-like effect of a single immune challenge in neuropeptide Y Y2 and Y4 receptor knockout mice

BMC Pharmacology ◽

10.1186/1471-2210-8-s1-a39 ◽

2008 ◽

Vol 8 (S1) ◽

Author(s):

Evelin Painsipp ◽

Herbert Herzog ◽

Günther Sperk ◽

Peter Holzer

Keyword(s):

Neuropeptide Y ◽

Knockout Mice ◽

Immune Challenge ◽

Long Term Depression ◽

Y4 Receptor

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Neuropeptide Y, social function and long-term outcome in schizophrenia

Schizophrenia Research ◽

10.1016/j.schres.2014.04.006 ◽

2014 ◽

Vol 156 (2-3) ◽

pp. 223-227 ◽

Cited By ~ 8

Author(s):

Gabriella Stålberg ◽

Lisa Ekselius ◽

Leif H. Lindström ◽

Dan Larhammar ◽

Robert Bodén

Keyword(s):

Neuropeptide Y ◽

Social Function ◽

Term Outcome ◽

Long Term Outcome

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Long-term effects of neuropeptide-Y on the rat adrenal cortex

Neuropeptides ◽

10.1016/0143-4179(90)90023-r ◽

1990 ◽

Vol 16 (1) ◽

pp. 9-13 ◽

Cited By ~ 10

Author(s):

B. Lesniewska ◽

M. Nowak ◽

B. Miskowiak ◽

G.G. Nussdorfer ◽

L.K. Malendowicz

Keyword(s):

Neuropeptide Y ◽

Adrenal Cortex ◽

Long Term Effects

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Combined Deletion of Y1, Y2, and Y4 Receptors Prevents Hypothalamic Neuropeptide Y Overexpression-Induced Hyperinsulinemia despite Persistence of Hyperphagia and Obesity

Endocrinology ◽

10.1210/en.2006-0097 ◽

2006 ◽

Vol 147 (11) ◽

pp. 5094-5101 ◽

Cited By ~ 43

Author(s):

En-Ju D. Lin ◽

Amanda Sainsbury ◽

Nicola J. Lee ◽

Dana Boey ◽

Michelle Couzens ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Neuropeptide Y ◽

Energy Homeostasis ◽

Viral Vector ◽

Body Weight Gain ◽

Hormonal Changes ◽

Obesity Syndrome ◽

Y Receptors

Neuropeptide Y (NPY) is a key regulator of energy homeostasis and is implicated in the development of obesity and type 2 diabetes. Whereas it is known that hypothalamic administration of exogenous NPY peptides leads to increased body weight gain, hyperphagia, and many hormonal and metabolic changes characteristic of an obesity syndrome, the Y receptor(s) mediating these effects is disputed and unclear. To investigate the role of different Y receptors in the NPY-induced obesity syndrome, we used recombinant adeno-associated viral vector to overexpress NPY in mice deficient of selective single or multiple Y receptors (including Y1, Y2, and Y4). Results from this study demonstrated that long-term hypothalamic overexpression of NPY lead to marked hyperphagia, hypogonadism, body weight gain, enhanced adipose tissue accumulation, hyperinsulinemia, and other hormonal changes characteristic of an obesity syndrome. NPY-induced hyperphagia, hypogonadism, and obesity syndrome persisted in all genotypes studied (Y1−/−, Y2−/−, Y2Y4−/−, and Y1Y2Y4−/− mice). However, triple deletion of Y1, Y2, and Y4 receptors prevented NPY-induced hyperinsulinemia. These findings suggest that Y1, Y2, and Y4 receptors under this condition are not crucially involved in NPY’s hyperphagic, hypogonadal, and obesogenic effects, but they are responsible for the central regulation of circulating insulin levels by NPY.

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Early dietary intervention: long-term effects on blood pressure, brain neuropeptide Y, and adiposity markers

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00505.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. E1236-E1243 ◽

Cited By ~ 81

Author(s):

Elena Velkoska ◽

Timothy J. Cole ◽

Margaret J. Morris

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Adipose Tissue ◽

Neuropeptide Y ◽

Litter Size ◽

High Fat Diet ◽

Dietary Intervention ◽

High Fat ◽

Brown Adipose

Early life nutrition impacts on subsequent risk of obesity and hypertension. Several brain chemicals responsible for both feeding and cardiovascular regulation are altered in obesity. We examined effects of early postnatal overnutrition on blood pressure, brain neuropeptide Y (NPY), and adiposity markers. Rat pup litters were adjusted to either 3 or 12 male animals (overnutrition and control, respectively) on day 1 of life. After weaning, rats were given either a palatable high-fat diet or standard chow. Smaller litter pups were significantly heavier by 17 days of age. By 16 wk, the effect of litter size was masked by that of diet, postweaning. Small and normal litter animals fed a high-fat diet had similar increases in body weight, plasma insulin, leptin, and adiponectin concentrations, leptin mRNA, and fat masses relative to chow-fed animals. An increase in 11β-hydroxysteroid dehydrogenase-1 mRNA in white adipose tissue, and a decrease in uncoupling protein-1 mRNA in brown adipose tissue in both small litter groups at 16 wk of age, may represent a programming effect of the altered litter size. NPY concentration in the paraventricular nucleus of the hypothalamus was reduced in high fat-fed groups. Blood pressure was significantly elevated at 13 wk in high-fat-fed animals. This study demonstrates that overnourishment during early postnatal development leads to profound changes in body weight at weaning, which tended to abate with maturation. Thus the effects of long-term dietary intervention postweaning can override those of litter size-induced obesity.

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