Hypothalamic Neuropeptide Expression of Juvenile and Middle-Aged Rats after Early Postnatal Food Restriction

Rats subjected to early postnatal food restriction (FR) show persistent changes in energy balance. The hypothalamus plays a major role in the regulation of energy balance. Therefore, we hypothesized that early postnatal food restriction induces developmental programming of hypothalamic gene expression of neuropeptides involved in this regulation. In the hypothalamus of juvenile and middle-aged rats that were raised in control (10 pups) or FR litters (20 pups), gene expression was investigated for neuropeptide Y (NPY), agouti-related protein (AgRP), proopiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART) in the arcuate nucleus (ARC); CRH and TRH in the paraventricular nucleus; and melanin-concentrating hormone (MCH) and orexin in the lateral hypothalamic area. Early postnatal FR acutely and persistently reduced body size. Juvenile FR rats had significantly reduced CART gene expression and increased MCH expression. In middle-aged FR rats, POMC and CART mRNA levels were significantly reduced. The ratio between expression of the ARC orexigenic peptides (NPY and AgRP) and anorexigenic peptides (POMC and CART) was increased in juvenile, but not in middle-aged, FR rats. These results suggest that in neonatal rats, FR already triggers the ARC, and to a lesser extent the lateral hypothalamic area, but not the paraventricular nucleus, to increase expression of orexigenic relative to anorexigenic peptides. In addition, with enduring small body size and normalized hypothalamic gene expression, the adult FR rats appeared to have accepted this smaller body size as normal. This suggests that the body weight set-point was differently programmed in animals with early postnatal FR.

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Lateral Hypothalamic Area Neurotensin Neurons Are Required for Control of Orexin Neurons and Energy Balance

Endocrinology ◽

10.1210/en.2018-00311 ◽

2018 ◽

Vol 159 (9) ◽

pp. 3158-3176 ◽

Cited By ~ 4

Author(s):

Juliette Brown ◽

Andrew Sagante ◽

Thomas Mayer ◽

Anna Wright ◽

Raluca Bugescu ◽

...

Keyword(s):

Body Weight ◽

Locomotor Activity ◽

Energy Balance ◽

Large Population ◽

Lateral Hypothalamic Area ◽

Hypothalamic Area ◽

Genetic Ablation ◽

Lateral Hypothalamic ◽

Adult Mice ◽

Locomotor Behaviors

Abstract The lateral hypothalamic area (LHA) is essential for motivated ingestive and locomotor behaviors that impact body weight, yet it remains unclear how the neurochemically defined subpopulations of LHA neurons contribute to energy balance. In particular, the role of the large population of LHA neurotensin (Nts) neurons has remained ambiguous due to the lack of methods to easily visualize and modulate these neurons. Because LHA Nts neurons are activated by leptin and other anorectic cues and they modulate dopamine or local LHA orexin neurons implicated in energy balance, they may have important, unappreciated roles for coordinating behaviors necessary for proper body weight. In this study, we genetically ablated or chemogenetically inhibited LHA Nts neurons in adult mice to determine their necessity for control of motivated behaviors and body weight. Genetic ablation of LHA Nts neurons resulted in profoundly increased adiposity compared with mice with intact LHA Nts neurons, as well as diminished locomotor activity, energy expenditure, and water intake. Complete loss of LHA Nts neurons also led to downregulation of orexin, revealing important cross-talk between the LHA Nts and orexin populations in maintenance of behavior and body weight. In contrast, chemogenetic inhibition of intact LHA Nts neurons did not disrupt orexin expression, but it suppressed locomotor activity and the adaptive response to leptin. Taken together, these data reveal the necessity of LHA Nts neurons and their activation for controlling energy balance, and that LHA Nts neurons influence behavior and body weight via orexin-dependent and orexin-independent mechanisms.

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Lateral hypothalamic area stimulation excites neurons in the region of the subfornical organ with efferent projections to the hypothalamic paraventricular nucleus in the rat

Brain Research ◽

10.1016/0006-8993(86)90278-7 ◽

1986 ◽

Vol 379 (1) ◽

pp. 200-203 ◽

Cited By ~ 32

Author(s):

Junichi Tanaka ◽

Hideto Kaba ◽

Hideo Saito ◽

Katsuo Seto

Keyword(s):

Paraventricular Nucleus ◽

Subfornical Organ ◽

Lateral Hypothalamic Area ◽

Hypothalamic Paraventricular Nucleus ◽

Hypothalamic Area ◽

Lateral Hypothalamic ◽

Efferent Projections

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The role of hypothalamic ingestive behavior controllers in generating dehydration anorexia: a Fos mapping study

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90425.2008 ◽

2008 ◽

Vol 295 (4) ◽

pp. R1009-R1019 ◽

Cited By ~ 11

Author(s):

Dawna Salter-Venzon ◽

Alan G. Watts

Keyword(s):

Paraventricular Nucleus ◽

Arcuate Nucleus ◽

Sensory Information ◽

Lateral Hypothalamic Area ◽

Ingestive Behavior ◽

Lateral Part ◽

Feeding Response ◽

Hypothalamic Area ◽

Lateral Hypothalamic ◽

Afferent Inputs

Giving rats 2.5% saline to drink for 3–5 days simply and reliably generates anorexia. Despite having the neurochemical and hormonal markers of negative energy balance, dehydrated anorexic rats show a marked suppression of spontaneous food intake, as well as the feeding that is usually stimulated by overnight starvation or a 2-deoxy-d-glucose (2DG) challenge. These observations are consistent with a dehydration-dependent inhibition of the core circuitry that controls feeding. We hypothesize that this inhibition is directed at those neurons in the paraventricular nucleus and lateral hypothalamic area that constitute the hypothalamic “behavior controller” for feeding rather than their afferent inputs from the arcuate nucleus or hindbrain that convey critical feeding-related sensory information. To test this hypothesis, we mapped and quantified the Fos-immunoreactive response to 2DG in control and dehydrated rats drinking 2.5% saline. Our rationale was that regions showing an attenuated Fos response to 2DG in dehydrated animals would be strong candidates as the targets of dehydration-induced suppression of 2DG feeding. We found that the Fos response to combined dehydration and 2DG was attenuated only in the lateral hypothalamic area, with dehydration alone increasing Fos in the lateral part of the paraventricular nucleus. In the arcuate nucleus and those regions of the hindbrain that provide afferent inputs critical for the feeding response to 2DG, the Fos response to 2DG was unaffected by dehydration. Therefore, dehydration appears to target the lateral hypothalamic area and possibly the lateral part of the paraventricular nucleus to suppress the feeding response to 2DG.

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