Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit
نویسندگان
چکیده
The nucleus of the solitary tract (NTS) is a key gateway for meal-related signals entering the brain from the periphery. However, the chemical mediators crucial to this process have not been fully elucidated. We reveal that a subset of NTS neurons containing cholecystokinin (CCK(NTS)) is responsive to nutritional state and that their activation reduces appetite and body weight in mice. Cell-specific anterograde tracing revealed that CCK(NTS) neurons provide a distinctive innervation of the paraventricular nucleus of the hypothalamus (PVH), with fibers and varicosities in close apposition to a subset of melanocortin-4 receptor (MC4R(PVH)) cells, which are also responsive to CCK. Optogenetic activation of CCK(NTS) axon terminals within the PVH reveal the satiating function of CCK(NTS) neurons to be mediated by a CCK(NTS)→PVH pathway that also encodes positive valence. These data identify the functional significance of CCK(NTS) neurons and reveal a sufficient and discrete NTS to hypothalamus circuit controlling appetite.
منابع مشابه
Mechanism of the induction of brain c-Fos-positive neurons by lipid absorption.
Many gastrointestinal meal-related signals are transmitted to the central nervous system via the vagus nerve and thereby control changes in meal size. The c-Fos-positive neuron has been used as a marker of neuronal activation after lipid meals to examine the contribution of a selective macronutrient on brain neurocircuit activity. In rats fed Intralipid, the c-Fos-positive neurons were highly s...
متن کاملA Parabrachial-Hypothalamic Cholecystokinin Neurocircuit Controls Counterregulatory Responses to Hypoglycemia
Hypoglycemia engenders an autonomically mediated counterregulatory (CR)-response that stimulates endogenous glucose production to maintain concentrations within an appropriate physiological range. Although the involvement of the brain in preserving normoglycemia has been established, the neurocircuitry underlying centrally mediated CR-responses remains unclear. Here we demonstrate that lateral ...
متن کاملPeripheral and central signals in the control of eating in normal, obese and binge-eating human subjects.
The worldwide increase in the incidence of obesity is a consequence of a positive energy balance, with energy intake exceeding expenditure. The signalling systems that underlie appetite control are complex, and the present review highlights our current understanding of key components of these systems. The pattern of eating in obesity ranges from over-eating associated with binge-eating disorder...
متن کاملSignificant Changes in the Activity of L-Glutamic Acid Decarboxylase of Mouse Hypothalamus After Peripheral Injection of Cholecystokinin-8 and Caerulein
The activity of one of the metabolizing enzymes of - aminobutyric acid, (GABA), was determined in mouse hypothalamus after peripheral injections of cholecystokinin-8 (CCK-8) and caerulein (CLN). The activity of this rate-limiting enzyme, L-glutamic acid decarboxylase, (GAD), did not change thirty minutes after peripheral injections of either CCK-8 or CLN in doses of 50g/kg body weight. Howeve...
متن کاملVagal Control of Satiety and Hormonal Regulation of Appetite
The paradigm for the control of feeding behavior has changed significantly. In this review, we present evidence that the separation of function in which cholecystokinin (CCK) controls short-term food intake and leptin regulate long-term eating behavior and body weight become less clear. In addition to the hypothalamus, the vagus nerve is critically involved in the control of feeding by transmit...
متن کامل