Leptin, which was previously discussed (Fig. 39.17), has effects on two types of neurons in the hypothalamus's arcuate nucleus. In the first type, leptin suppresses the production of neuropeptide Y (NPY), a potent stimulator of food-seeking behavior (energy intake) and an inhibitor of energy expenditure. Some of these neurons also co-localize norepinephrine, another appetite stimulator, with NPY. At the same time, leptin inhibits the production of agouti-related peptide (AGRP), which acts on MC4R, a receptor for the anorexigenic peptide α-melanocyte–stimulating hormone (α-MSH), which inhibits food intake. In the second type of arcuate neuron, leptin stimulates the production of proopiomelanocortin (POMC) products, including α-MSH, and cocaine-amphetamine–regulated transcript (CART), both of which suppress food intake. Thus, leptin regulates energy expenditure by simultaneously inhibiting NPY and α-MSH. These neuropeptides are transmitted to and interact with receptors in neurons of the paraventricular nucleus and lateral hypothalamic nucleus, which are known as "hunger" neurons. Additionally, leptin influences activity (especially sympathetic outflow) and various endocrine actions on thyroid gland function, reproduction, and growth.

Another regulator of food intake and body energy stores is melanin-concentrating hormone (MCH). MCH antagonizes the satiety effect of α-MSH downstream from the interaction of α-MSH with its MC4R receptor. The importance of MCH is evident from the fact that its ablation by gene knockout results in leanness.

To maintain overall energy homeostasis, the system must balance nutrient intake with nutrient oxidation. Serotonin produces satiety after glucose ingestion, while gastrointestinal hormones like cholecystokinin and GLP-1 produce satiety through humoral effects, although their local production in the brain may also participate in nutrient and caloric regulation. Ghrelin, a recently discovered hormone, is an acylated peptide with potent orexigenic activity. It is produced by cells in the stomach's oxyntic glands. Plasma ghrelin levels rise in humans 1 to 2 hours before meals and fall drastically about 1 hour after eating. Ghrelin stimulates food intake by acting on its receptor in hypothalamic neurons expressing NPY.

1. Cells generate ATP to meet their energy requirements through glycolysis and the TCA cycle coupled to oxidative phosphorylation.
2. Cells can oxidize carbohydrates (primarily glucose), amino acids (AAs), and free fatty acids (FFAs) to produce ATP. During fasting, the liver also produces ketone bodies (KBs) for other tissues to oxidize for energy.
3. Some cell types have limitations in the energy substrates they can utilize for energy production. The brain, for example, is exclusively dependent on glucose. Therefore, maintaining blood glucose levels above 60 mg/dL is necessary for normal autonomic and CNS function. Conversely, excessively high glucose levels (fasting glucose > 100 mg/dL) promote glucotoxicity and contribute to the long-term complications of diabetes.
4. The endocrine pancreas secretes insulin, glucagon, somatostatin, gastrin, and pancreatic polypeptide.
5. Insulin, an anabolic hormone, is released during periods of excess nutrient availability. It facilitates the utilization of carbohydrates as energy sources and promotes nutrient storage.
6.
Fig. 39.17 ), already discussed. Leptin acts on at least two neuron types in the arcuate nucleus of the hypothalamus. In the first, leptin represses production of neuropeptide Y (NPY), a very potent stimulator of food- seeking behavior (energy intake) and an inhibitor of energy expenditure. Norepinephrine, another appetite stimulator, co-localizes with NPY in some of these neurons. At the same time, leptin represses production of agouti-related peptide (AGRP), an endogenous antagonist that acts on
MC4R, a hypothalamic receptor for the anorexigenic peptide α-melanocyte–stimulating hormone (α-MSH), which inhibits food intake. In another type of arcuate neuron, leptin stimulates production of proopiomelano cortin (POMC) products, one of which is α-MSH, and production of cocaine-amphetamine–regulated transcript (CART), both of which inhibit food intake. Thus leptin diture by simultaneously inhibiting NPY and the α-MSH
Fig. 39.17 ). These second-order neuropeptides are transmitted to and interact with receptors in neurons of the and lateral hypothalamic nucleus (“hunger” neurons). In activity (especially sympathetic outflow) with diverse endo crine actions on thyroid gland function, reproduction, and growth.
Another regulator of food intake and body energy stores is melanin-concentrating hormone (MCH). This antagonizing the satiety effect of α-MSH downstream from the interaction of α-MSH with its MC4R receptor. The probable importance of this molecule is demonstrated by the fact that it is the only regulator whose ablation by gene knockout actually results in leanness.
To maintain overall energy homeostasis, the system must example, carbohydrate intake with carbohydrate oxidation.
neurotransmitter responses to meals. Serotonin produces satiety after ingestion of glucose. Gastrointestinal hormones such as cholecystokinin and GLP-1 produce satiety by humoral effects, but their local production in the brain may participate in nutrient and caloric regulation. The recently discovered hormone ghrelin is an acylated peptide with potent orexigenic activity that arises in cells of the oxyntic glands in the stomach. Plasma levels of ghrelin rise in humans in the 1 to 2 hours that precede their normal meals.
Plasma levels of ghrelin fall drastically to minimum values about 1 hour after eating. Ghrelin appears to stimulate food intake by reacting with its receptor in hypothalamic neurons that express NPY.
1.
Cells make ATP to meet their energy needs. ATP is made by glycolysis and by the TCA cycle coupled to oxidative phosphorylation.
2.
Cells can oxidize carbohydrate (primarily in the form of glucose), AAs, and FFAs to make ATP. Additionally the liver makes KBs for other tissues to oxidize for energy in times of fasting.
3.
Some cell types are limited in the energy substrates they can oxidize for energy. The brain is normally exclusively dependent on glucose for energy. Thus blood glucose must be maintained above 60 mg/ dL for normal autonomic and CNS function. Conversely, inappropriately high levels of glucose (i.e., fasting glucose > 100 mg/dL) promote glucotoxicity and thereby lead to the long-term complications of diabetes.
4.
The endocrine pancreas produces the hormones insulin, glucagon, somatostatin, gastrin, and pancreatic polypeptide.
5.
Insulin is an anabolic hormone that is secreted in times of excess nutrient availability. It allows the body to use carbohydrates as energy sources and store nutrients.
6.