Atypical antipsychotics and the neural regulation of food intake and peripheral metabolism

Abstract Context: The endocannabinoid (eCB) system is involved in the regulation of food intake and of peripheral metabolism. Although the cross talk between energy metabolism and the circadian system is well documented, little is known about a potential circadian modulation of human eCB activity. Objective: The objective of the study was to define the 24-hour profile of circulating levels of the most abundant endogenous ligand of the CB1 receptor, 2-arachidonoylglycerol (2-AG), in healthy young nonobese adults studied under controlled bedtime, dietary, and activity conditions. Methods: Fourteen subjects participated in this 4-day laboratory study with fixed light-dark cycles, standardized meals, and bedtimes. Sleep was recorded each night. On the third day, blood sampling at 15- to 30-minute intervals began at 9:30 pm and continued for 24 hours. Cortisol, leptin, and ghrelin were assayed on all samples, whereas the levels of 2-AG and its structural analog, 2-oleoylglycerol (2-OG), were measured at 60-minute intervals. Results: All participants exhibited a large circadian variation of 2-AG serum concentrations with a nadir around midsleep, coincident with the middle of the overnight fast. Levels of 2-AG increased continually across the morning, peaking in the early to midafternoon. Peak values represented, on average, a nearly 3-fold increase above nocturnal nadir levels. Concentrations of 2-OG followed a similar pattern, although with a shorter morning increase and lower amplitude. Conclusions: The findings demonstrate that activity of the eCB system is profoundly modulated by circadian rhythmicity and suggest that its impact on the regulation of food intake is suppressed during sleep and is maximal during early to midafternoon.

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A novel satiety sensor detects circulating glucose and suppresses food consumption via insulin-producing cells in Drosophila

Cell Research ◽

10.1038/s41422-020-00449-7 ◽

2020 ◽

Author(s):

Wei Qi ◽

Gaohang Wang ◽

Liming Wang

Keyword(s):

Food Intake ◽

Food Consumption ◽

Energy Homeostasis ◽

Animal Species ◽

Suppressive Effect ◽

Food Ingestion ◽

Neural Regulation ◽

Insulin Producing Cells ◽

Survival Skill ◽

Regulate Food Intake

AbstractSensing satiety is a crucial survival skill for all animal species including human. Despite the discovery of numerous neuromodulators that regulate food intake in Drosophila, the mechanism of satiety sensing remains largely elusive. Here, we investigated how neuropeptidergic circuitry conveyed satiety state to influence flies’ food consumption. Drosophila tackykinin (DTK) and its receptor TAKR99D were identified in an RNAi screening as feeding suppressors. Two pairs of DTK+ neurons in the fly brain could be activated by elevated D-glucose in the hemolymph and imposed a suppressive effect on feeding. These DTK+ neurons formed a two-synapse circuitry targeting insulin-producing cells, a well-known feeding suppressor, via TAKR99D+ neurons, and this circuitry could be rapidly activated during food ingestion and cease feeding. Taken together, we identified a novel satiety sensor in the fly brain that could detect specific circulating nutrients and in turn modulate feeding, shedding light on the neural regulation of energy homeostasis.

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NEURAL REGULATION OF FOOD INTAKE

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1955.tb36544.x ◽

1955 ◽

Vol 63 (1) ◽

pp. 44-55 ◽

Cited By ~ 88

Author(s):

John R. Brobeck

Keyword(s):

Food Intake ◽

Neural Regulation

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Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism

International Journal of Molecular Sciences ◽

10.3390/ijms15011499 ◽

2014 ◽

Vol 15 (1) ◽

pp. 1499-1510 ◽

Cited By ~ 7

Author(s):

Wanchun Yang ◽

Wanxiang Jiang ◽

Liping Luo ◽

Jicheng Bu ◽

Dejiang Pang ◽

...

Keyword(s):

Food Intake ◽

Genetic Deletion ◽

The Brain ◽

Peripheral Metabolism

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Influence of fatty acid oxidation in lateral hypothalamus on food intake and body composition

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.261.2.r339 ◽

1991 ◽

Vol 261 (2) ◽

pp. R339-R343 ◽

Cited By ~ 1

Author(s):

J. L. Beverly ◽

R. J. Martin

Keyword(s):

Body Composition ◽

Fatty Acid ◽

Food Intake ◽

Fatty Acid Oxidation ◽

Serum Levels ◽

Ventromedial Hypothalamus ◽

Acid Oxidation ◽

Oxidation Rates ◽

Energy Stores ◽

Peripheral Metabolism

This study tested the concept that the level of fatty acid oxidation in the ventrolateral hypothalamus (VLH) reflects peripheral energy stores and elicits compensatory responses to changes in energy balance status. Fatty acid oxidation rates in the VLH were chronically altered over a 14-day period by infusing into the VLH either 0.1 mM 4-pentenoic acid (4-PA; 5 ng/h) or 1.0 mM L-carnitine (L-Carn; 98 ng/h). Fatty acid oxidation rates in the VLH were altered to a similar extent as by overfeeding (reduced 37% by 4-PA) and dietary restriction (increased 28% by L-Carn). Diffusion of infusates was limited, since there were normal rates of fatty acid oxidation in the ventromedial hypothalamus and cortex. There were no significant effects of altering fatty acid oxidation in the VLH on food intake, body weight, body composition, or serum levels of glucose, insulin, and free fatty acids. The results of this experiment indicate that the level of fatty acid oxidation in the VLH is unlikely to independently elicit changes in food intake or peripheral metabolism.

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Food intake and peripheral factors after recovery from insulin-induced hypoglycemia

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1983.244.3.r374 ◽

1983 ◽

Vol 244 (3) ◽

pp. R374-R382 ◽

Cited By ~ 2

Author(s):

M. I. Friedman ◽

J. Granneman

Keyword(s):

Food Intake ◽

Plasma Glucose ◽

Insulin Treatment ◽

Hepatic Metabolism ◽

Insulin Injection ◽

Hypoglycemic Episode ◽

Glucose Levels ◽

Metabolic Variables ◽

Peripheral Metabolism

Rats increased food intake after plasma glucose returned to normal in the wake of an insulin-induced hypoglycemic episode. Whereas increased eating 6–8 h after insulin occurred only when plasma glucose levels fell below 70 mg/dl, intakes were not related to the degree of prior hypoglycemia. Administration of glucose in the first 3 h after insulin prevented increased eating, whereas glucose given 4–6 h after insulin was less effective. Intravenous infusions of fructose given in the first 3 h after insulin injection prevented increased food intake in normal but not hepatic-vagotomized rats. Determination of various metabolic variables in parallel experiments showed that insulin treatment resulted in changes in peripheral metabolism, which persisted at the time feeding tests were conducted, and that administration of glucose or fructose tended to reverse these changes. The results suggest that increased food intake after recovery from hypoglycemia is associated with peripheral metabolic consequences of ongoing or previous counterregulatory responses which occur during hypoglycemia and that alterations in hepatic metabolism are sufficient to inhibit this insulin-induced eating.

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Fine Structural Alterations in Thyroid Follicular Cells (FC) and Changes in Serum Thyroxine Produced by Feeding Polychlorinated Biphenyl (PCB) to Rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100079929 ◽

1977 ◽

Vol 35 ◽

pp. 498-499

Author(s):

W.T. Collins ◽

Charles C. Capen ◽

Louis Kasza

Keyword(s):

Feed Efficiency ◽

Polychlorinated Biphenyl ◽

Serum Proteins ◽

Skin Lesions ◽

Hepatic Necrosis ◽

Ultrastructural Changes ◽

Lymphoid Tissues ◽

Heat Transfer Fluids ◽

Thyroid Follicular Cells ◽

Peripheral Metabolism

The widespread contamination of the environment with PCB, a compound used extensively by industry in hydraulic and heat transfer fluids as well as plasticizers and solvents in adhesives and sealants, has resulted in detectable tissue levels in a large portion of the human population, domestic animals, and wildlife. Intoxication with PCB produces severe hepatic necrosis, degeneration of lymphoid tissues and kidney, skin lesions, decreased reproductive performance, reduced feed efficiency, and decreased weight gain. PCB also has been reported to reduce the binding of thyroid hormone to serum proteins and enhance the peripheral metabolism of thyroxine with increased excretion of thyroxine-glucuronide in the bile (Bastomsky, Endocrinology 95: 1150-1155, 1974).The objectives of this investigation were (1) to investigate the histopathologic, histochemical, and ultrastructural changes in thyroid FC produced by the acute (4 week) and chronic (12 week) administration of low (50 ppm) and high (500 ppm) doses of PCB to rats, (2) to correlate these alterations to changes in serum immunoreactive thyroxine concentration, and (3) to investigate the persistence of the effects of PCB on the thyroid gland.

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Obesity and adiposity: the culprit of dietary protein efficacy

Clinical Science ◽

10.1042/cs20190583 ◽

2020 ◽

Vol 134 (4) ◽

pp. 389-401

Author(s):

Carla El-Mallah ◽

Omar Obeid

Keyword(s):

Food Intake ◽

Behavioural Change ◽

Physiological Mechanism ◽

Short Term ◽

The Past ◽

Body Adiposity ◽

Reduce Sugar ◽

Eye Opening ◽

Potential Strategy ◽

Limitations And Exceptions

Abstract Obesity and increased body adiposity have been alarmingly increasing over the past decades and have been linked to a rise in food intake. Many dietary restrictive approaches aiming at reducing weight have resulted in contradictory results. Additionally, some policies to reduce sugar or fat intake were not able to decrease the surge of obesity. This suggests that food intake is controlled by a physiological mechanism and that any behavioural change only leads to a short-term success. Several hypotheses have been postulated, and many of them have been rejected due to some limitations and exceptions. The present review aims at presenting a new theory behind the regulation of energy intake, therefore providing an eye-opening field for energy balance and a potential strategy for obesity management.

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