Regulation of Hunger and Satiety PDF

The Regulation of Hunger and Satiety Prof. Dr. Haluk KELEŞTİMUR Istanbul Okan University Medical School Department of Physiology Descriptions of hunger and satiety    Hunger is a feeling caused by lack of food. It is an important signal, saying to the body about the need for food intake and energ...

The Regulation of Hunger and Satiety Prof. Dr. Haluk KELEŞTİMUR Istanbul Okan University Medical School Department of Physiology Descriptions of hunger and satiety    Hunger is a feeling caused by lack of food. It is an important signal, saying to the body about the need for food intake and energy from it. Satiety is the feeling of fullness and the suppression of hunger for a period of time after a meal. Appetite is the desire for food. Prevalence of adult overweight & obesity (%) - World Obesity A sample of Complications of Obesity The hypothalamus is the brain’s appetite control center. Structure of Hypothalamus Hypothalamic Nuclei and Its Functions The centres of hunger and satiety are located in the hypothalamus Dorsomedial hypothalamus (DMH) provides the relationship between satiety and hunger centers. Neuropeptides Involved in Control of Food Intake and Metabolism Peripheral Peptides Involved in Control of Food Intake and Metabolism Orexinergic and anorexinergic neurotransmitters and hormones that influence hunger and satiety centers in the hypothalamus Metabolic Pathways During the Fasting Phase and Absorptive Phase of Metabolism Absorptive phase. During the absorptive phase the activity of parasympathetic nervous system (Rest and digest) increases, and the activity of the sympathetic nervous system falls. We receive glucose, amino acids, and fats from the intestines. The blood level of insülin is high, which permits all cells to metabolize glucose. In addition, the liver and the muscles convert glucose to glycogen, which replenishes the short-term reservoir. Excess carbohydrates and amino acids are converted to fats, and fats are placed into the long-term reservoir in the adipose tissue. Effects of Insulin and Glucagon on Glucose and Glycogen (cont’d) Fasting phase. During the fasting phase the activity of the parasympathetic nervous system falls, and the activity of the sympathetic nervous system (Fight or flight) increases. In response, the level of insulin decreases, and the levels of glucagon and the adrenal catecholamines rise. These events cause liver glycogen to be converted to glucose and triglycerides to be broken down into glycerol and fatty acids. In the absence of insulin, only the central nervous system can use the glucose that is available in the blood; the rest of the body lives on fatty acids. Glycerol is converted to glucose by the liver, and the glucose is metabolized by the brain. Effects of Insulin and Glucagon on Glucose and Glycogen Neural circuitries concerned with the control of drinking and eating The connections of the melanin concentrating hormone (MCH) neurons and orexin neurons of the lateral hypothalamus Melanin-concentrating hormone (MCH). A peptide neurotransmitter found in a system of lateral hypothalamic neurons that stimulate appetite and reduce metabolic rate. Orexin. A peptide neurotransmitter found in a system of lateral hypothalamic neurons that stimulate appetite and reduce metabolic rate. The connections of the NPY neurons of the arcuate nucleus. Activity of MCH and orexin neurons of the lateral hypothalamus increases food intake and decreases metabolic rate. These neurons are activated by NPY/AGRP-secreting neurons of the arcuate nucleus, which are sensitive to ghrelin and which receive excitatory input from NPY neurons in the medulla that are sensitive to glucoprivation. The NPY/AGRP neurons of the arcuate nucleus also project to the paraventricular nucleus, which plays a role in control of insulin secretion and metabolism. The endocannabinoids stimulate appetite by increasing the release of MCH and orexin. Control of energy balance by two types of neurons of the arcuate nuclei Pro-opiomelanocortin (POMC) neurons that release alphamelanocyte–stimulating hormone (α-MSH) and cocaine- and amphetamine-regulated transcript (CART), decreasing food intake and increasing energy expenditure. Neurons that produce agoutirelated protein (AGRP) and neuropeptide Y (NPY), increasing food intake and reducing energy expenditure. (cont’d) α-MSH released by POMC neurons stimulates melanocortin receptors (MCR-3 and MCR-4) in the paraventricular nuclei (PVN), which then activate neuronal pathways that project to the nucleus tractus solitarius (NTS) and increase sympathetic activity and energy expenditure. AGRP acts as an antagonist of MCR-4. Insulin, leptin, and cholecystokinin (CCK) are hormones that inhibit AGRP-NPY neurons and stimulate adjacent POMC-CART neurons, thereby reducing food intake. Ghrelin, a hormone secreted from the stomach, activates AGRP-NPY neurons and stimulates food intake. First-order neurons in arcuate nucleus of hypothalamus The arcuate nucleus has two subsets of neurons that function in an opposing manner. One subset releases neuropeptide Y (NPY), and the other releases melanocortins derived from proopiomelanocortin (POMC), a precursor molecule that can be cleaved in different ways to produce several hormone products. NPY, one of the most potent appetite stimulators ever found, leads to increased food intake, thus promoting weight gain. Melanocortins, most notably amelanocyte stimulating hormone (a-MSH) from the hypothalamus, suppress appetite, thus leading to reduced food intake and weight loss. Second-order neurons in the hypothalamus Two hypothalamic areas are richly supplied by axons from the NPY and a-MSH neurons of the arcuate nucleus. These second-order neuronal areas involved in energy balance and food intake are the lateral hypothalamic area (LHA) and paraventricular nucleus (PVN). The LHA produces orexins, which are potent stimulators of food intake. NPY stimulates and melanocortins inhibit the release of appetite-enhancing orexins. By contrast, the PVN releases chemical messengers, for example, corticotropin-releasing hormone (CRH), that decrease appetite and food intake. Melanocortins stimulate and NPY inhibits the release of these appetite-suppressing chemicals. Short-Term Eating Behavior Two blood-borne peptides secreted by the digestive tract that are important in regulating how often and how much we eat in a given day are ghrelin and peptide YY3-36 (PYY336), which signify hunger and fullness, respectively. Ghrelin, the so-called hunger hormone, is a potent appetite stimulator produced by the stomach. Ghrelin stimulates appetite by activating the hypothalamic NPYsecreting neurons. PYY3-36 is a counterpart of ghrelin. The secretion of PYY3-36, which is produced by the small and large intestines, is at its lowest level before a meal but rises during meals and signals satiety. This peptide acts by inhibiting the appetite stimulating NPY secreting neurons in the arcuate nucleus. Long-Term Maintenance of Energy Balance The arcuate nucleus is the major site for leptin (an adipokine) action. Leptin suppresses appetite, thus decreasing food consumption and promoting weight loss, by inhibiting hypothalamic output of appetitestimulating NPY and stimulating output of appetite suppressing melanocortins. The leptin signal is generally considered the dominant factor responsible for the long-term matching of food intake to energy expenditure so that total body energy content remains balanced and body weight remains constant. Long-Term Maintenance of Energy Balance Another blood-borne signal besides leptin that plays an important role in long-term control of body weight is insulin. Insulin, a hormone secreted by the pancreas in response to a rise in the concentration of glucose and other nutrients in the blood following a meal, stimulates cellular uptake, use, and storage of these nutrients. Thus, the increase in insulin secretion that accompanies nutrient abundance, use, and storage appropriately inhibits the NPY-secreting cells of the arcuate nucleus, thus suppressing further food intake. Satiety center in brain stem In addition to the key role the hypothalamus plays in maintaining energy balance, a satiety center in the brain stem known as the nucleus tractus solitarius (NTS) processes signals important in the feeling of being full and thus contributes to short-term control of meals. Not only does the NTS receive input from the higher hypothalamic neurons involved in energy homeostasis, but it also receives afferent inputs from the digestive tract (for example, afferent input indicating the extent of stomach distension) and elsewhere that signal satiety. Cholecystokinin as a Satiety Signal 1. CCK is one of the gastrointestinal hormones released from the duodenal mucosa during digestion of a meal and is an important satiety signal for regulating meal size. 2. CCK is secreted in response to the presence of nutrients in the small intestine. It contributes to the sense of being filled after a meal has been consumed but before it has been digested and absorbed. This explains why we stop eating before the ingested food is made available to meet the body’s energy needs. 3. Other related, more recently discovered gut peptides released in response to a meal that serve as satiety signals include glucagon like peptide 1 (GLP 1) and oxyntomodulin. Psychosocial and Environmental Influences Often our decision to eat or stop eating is not determined merely by whether we are hungry or full, respectively. Eating foods with an enjoyable taste, smell, and texture can increase appetite and food intake. Stress, anxiety, depression, and boredom have also been shown to alter feeding behavior in ways unrelated to energy needs. People often eat to satisfy psychological needs rather than to satisfy hunger. Furthermore, environmental influences, such as the amount of food available, play an important role in determining the extent of food intake. Thus, any comprehensive explanation of how food intake is controlled must take into account these voluntary eating acts that can reinforce or override the internal signals governing feeding behavior. The homeostatic control of food intake upon peripheric signals The reward system controlling non-homeostatic food intake Food intake is also influenced by non-homeostatic signals, inducing food intake for pleasure. The hedonic intake of food depends mainly on taste, odor, texture, and appearance. The reward system can lead to overeating and positive energy balance and induce obesity. The reward system involves the mesocorticolimbic pathway that includes dopaminergic neurons located in the VTA and their axons projecting to the striatum, including the Nac and to the prefrontal cortex (PFC).