The Need to Feed Homeostatic and Hedonic Control of Eating

AbstractFeeding provides substrate for energy metabolism, which is vital to the survival of every living animal and therefore is subject to intense regulation by brain homeostatic and hedonic systems. Over the last decade, our understanding of the circuits and molecules involved in this process has changed dramatically, in large part due to the availability of animal models with genetic lesions. In this review, we examine the role played in homeostatic regulation of feeding by systemic mediators such as leptin and ghrelin, which act on brain systems utilizing neuropeptide Y, agouti-related peptide, melanocortins, orexins, and melanin concentrating hormone, among other mediators. We also examine the mechanisms for taste and reward systems that provide food with its intrinsically reinforcing properties and explore the links between the homeostatic and hedonic systems that ensure intake of adequate nutrition

Atrial natriuretic peptide inhibits evoked catecholamine release by altering sensitivity to calcium.

ABSTRACT Natriuretic peptides are cyclized peptides produced by cardiovascular and neural tissues. These peptides inhibit various secretory responses such as the release of renin, aldosterone and autonomic neurotransmitters. This report tests the hypothesis that atrial natriuretic peptide reduces dopamine efflux from an adrenergic cell line, rat pheochromocytoma cells, by suppressing intracellular calcium concentrations. The L-type calcium channel inhibitor, nifedipine, markedly suppressed dopamine release from depolarized PC12 cells, suggesting that calcium entering through this channel was the predominant stimulus for dopamine efflux. Atrial natriuretic peptide maximally reduced depolarization-evoked dopamine release 20 Ϯ 3% at a concentration of 100 nM and this effect was abolished by nifedipine, but not by pretreatment with the N-type calcium channel inhibitor, -conotoxin, or an inhibitor of calcium-induced calcium release, ryanodine. In cells loaded with Fura-2, atrial natriuretic peptide both augmented depolarization-induced increases of intracellular free calcium concentrations and accelerated the depolarization-induced quenching of the Fura-2 signal by manganese, findings consistent with enhanced conductivity of calcium channels. Dopamine efflux induced by either the calcium ionophore, A23187, or staphylococcal ␣ toxin was attenuated by atrial natriuretic peptide. Additionally, a natriuretic peptide interacting solely with the natriuretic peptide C receptor in these cells, C-type natriuretic peptide, also suppressed calcium-induced dopamine efflux in permeabilized cells. These data are consistent with natriuretic peptides attenuating catecholamine exocytosis in response to calcium but inconsistent with the neuromodulatory effect resulting from a reduction in intracellular calcium concentrations within pheochromocytoma cells. Atrial natriuretic peptide, the first member of the natriuretic peptide family to be identified Because calcium is typically the stimulus for neurotransmitter release from neuron

Next-generation crossover-free quantum Hall arrays with superconducting interconnections

This work presents precision measurements of quantized Hall array resistance devices using superconducting, crossover-free and multiple interconnections as well as graphene split contacts. These new techniques successfully eliminate the accumulation of internal resistances and leakage currents that typically occur at interconnections and crossing leads between interconnected devices. As a result, a scalable quantized Hall resistance array is obtained with a nominal value that is as precise and stable as that from single-element quantized Hall resistance standards

Two-Terminal and Multi-Terminal Designs for Next-Generation Quantized Hall Resistance Standards: Contact Material and Geometry

In this paper, we show that quantum Hall resistance measurements using two terminals may be as precise as four-terminal measurements when applying superconducting split contacts. The described sample designs eliminate resistance contributions of terminals and contacts such that the size and complexity of next-generation quantized Hall resistance devices can be significantly improved

Melanocortin 4 Receptors Reciprocally Regulate Sympathetic and Parasympathetic Preganglionic Neurons

Melanocortin 4 receptors (MC4Rs) in the central nervous system are key regulators of energy and glucose homeostasis. Notably, obese patients with MC4R mutations are hyperinsulinemic and resistant to obesity-induced hypertension. Although these effects are likely dependent upon the activity of the autonomic nervous system, the cellular effects of MC4Rs on parasympathetic and sympathetic neurons remain undefined. Here, we show that MC4R agonists inhibit parasympathetic preganglionic neurons in the brainstem. In contrast, MC4R agonists activate sympathetic preganglionic neurons in the spinal cord. Deletion of MC4Rs in cholinergic neurons resulted in elevated levels of insulin. Furthermore, re-expression of MC4Rs specifically in cholinergic neurons (including sympathetic preganglionic neurons) restores obesity-associated hypertension in MC4R null mice. These findings provide a cellular correlate of the autonomic side effects associated with MC4R agonists and demonstrate a role for MC4Rs expressed in cholinergic neurons in the regulation of insulin levels and in the development of obesity-induced hypertension

Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis

Intrauterine growth restriction (IUGR) is closely linked with metabolic diseases, appetite disorders and obesity at adulthood. Leptin, a major adipokine secreted by adipose tissue, circulates in direct proportion to body fat stores, enters the brain and regulates food intake and energy expenditure. Deficient leptin neuronal signalling favours weight gain by affecting central homeostatic circuitry. The aim of this study was to determine if leptin resistance was programmed by perinatal nutritional environment and to decipher potential cellular mechanisms underneath

Accessing ratios of quantized resistances in graphene p–n junction devices using multiple terminals

The utilization of multiple current terminals on millimeter-scale graphene p–n junction devices has enabled the measurement of many atypical, fractional multiples of the quantized Hall resistance at the ν = 2 plateau (RH ≈ 12 906 Ω). These fractions take the form abRH and can be determined both analytically and by simulations. These experiments validate the use of either the LTspice circuit simulator or the analytical framework recently presented in similar work. Furthermore, the production of several devices with large-scale junctions substantiates the approach of using simple ultraviolet lithography to obtain junctions of sufficient sharpness.The utilization of multiple current terminals on millimeter-scale graphene p–n junction devices has enabled the measurement of many atypical, fractional multiples of the quantized Hall resistance at the ν = 2 plateau (RH ≈ 12 906 Ω). These fractions take the form abRH and can be determined both analytically and by simulations. These experiments validate the use of either the LTspice circuit simulator or the analytical framework recently presented in similar work. Furthermore, the production of several devices with large-scale junctions substantiates the approach of using simple ultraviolet lithography to obtain junctions of sufficient sharpness