Regulation of Food Intake & Metabolism and Energy Balance 2024 PDF

Regulation of Food Intake & Metabolism and Energy Balance 2024 Learning outcomes At the end of the lecture, students will be able to 1. Explain how food intake is regulated by hypothalamic centers 2. Name the hypothalamic nuclei that regulates food intake 3. List the factors that regulate food intak...

Regulation of Food Intake & Metabolism and Energy Balance 2024 Learning outcomes At the end of the lecture, students will be able to 1. Explain how food intake is regulated by hypothalamic centers 2. Name the hypothalamic nuclei that regulates food intake 3. List the factors that regulate food intake 4. Explain how hormones released from gastrointestinal system regulate food intake 5. Explain the role of leptin in food intake regulation 6. Discuss what would happen when the food intake regulation system fails 7. Define basal metabolic rate (BMR) and how we can measure BMR Maintenance of adequate energy supply in the body is critical, There are multiple short-term and long-term control systems that regulate food intake and, also energy expenditure and energy stores Calories consumed (Energy intake) Resting metabolism Activity & Exercise consumed (Energy expenditure) Stability of the body’s total mass long periods requires that energy intake match energy expenditure How? What if the food intake regulation system fails … Obesity models One monogenic model is the Ob/Ob strain of hyperphagic mice. In the experiments, the Ob/Ob mouse was surgically connected to a wild-type mouse. In parabiotically coupled mice, ~1% of the cardiac output of one mouse goes to the other, and vice versa ★ the animals exchange blood-borne factors. The Ob (obese) mouse lost weight. Obesity models Why/How obese (Ob) mouse lost weight? The Ob/Ob mouse lost weight, which suggests that such mice lack a blood-borne factor/s. Another model of obesity (B) Connecting a Db/Db and a wild-type mouse No change in Db mouse the wild-type mouse starved Why? 1. The Db mouse makes an excess of the blood-borne factor 2. The Db mouse lacks the receptor for this factor 3. Absence of the receptor in the Db mouse removes the negative feedback, which leads to high levels of the blood-borne factor. Ob: Obese; Wt: wild type; Db: it secondarily develops type 2 diabetes Regulation of food intake The intake of nutrients is under complex control involving signals from both the periphery and the central nervous system. Food preferences, emotions, environment, lifestyle, and circadian rhythms may all have profound effects on whether food is sought, and the type of food that is ingested. The sensation of hunger is associated with a craving for food and several other physiological effects, e.g., rhythmic contractions of the stomach, cause the person to seek food. After a meal, the feeling of satiety occurs. These feelings are influenced by environmental and cultural factors, as well as by physiological controls that influence specific centers of the brain, especially the hypothalamus. Regulation of food intake In the brain – Feeding center – Satiety center (+ limbic system & cerebral cortex) Brain – GIS hormones Adipocytes, Adrenal gland Hypothalamus The hypothalamus maintains homeostasis by regulating a variety of visceral activities and by linking the nervous and endocrine systems. The hypothalamus also regulates: 1. Heart rate and arterial blood pressure 2. Body temperature 3. Water and electrolyte balance 4. Control of hunger and body weight 5. Control of movements and glandular secretions of the stomach and intestines 6. Production of neurosecretory substances that stimulate the pituitary gland to secrete hormones 7. Sleep and wakefulness The Hypothalamus Contains Hunger and Satiety Centers The lateral nuclei of the hypothalamus serve as a feeding center - stimulation of this area causes an animal to eat voraciously (hyperphagia). Destruction of the lateral hypothalamus causes lack of desire for food and progressive inanition, a condition characterized by marked weight loss, muscle weakness, and decreased metabolism The ventromedial nuclei of the hypothalamus serve as the satiety center It inhibits the feeding center. Electrical stimulation of this region can cause complete satiety, and even in the presence of highly appetizing food, the animal refuses to eat (aphagia). Destruction of the ventromedial nuclei causes voracious and continued eating until the animal becomes extremely obese, sometimes weighing as much as four times normal. CENTERS in HYPOTHALAMUS (hunger center) (Satiety center) Arcuate nuclues (ARC) is an integration center. It gives rise to either decreased food intake or increased food intake. The paraventricular, dorsomedial, and arcuate nuclei of the hypothalamus also play a major role in regulating food intake lesions of the paraventricular nuclei often cause excessive eating, lesions of the dorsomedial nuclei usually depress eating behavior. the arcuate nuclei - multiple hormones released from the gastrointestinal tract and adipose tissue converge to regulate food intake, as well as energy expenditure. Hypothalamic feeding and satiety centers have a high density of receptors for neurotransmitters and hormones that influence feeding behavior These hypothalamic areas also influence the secretion of hormones, particularly from the thyroid gland, adrenal gland, and pancreatic islet cells, in response to changing metabolic demands. The hypothalamus regulates caloric intake, usage, and storage and maintain the body weight in adulthood. The hypothalamus receives neural signals from the GI tract (stomach filling); - chemical signals from nutrients in the blood (glucose, amino acids, and fatty acids); -signals from gastrointestinal hormones; - signals from hormones released by adipose tissue; and - signals from the cerebral cortex (sight, smell, and taste) that influence feeding behavior. - signals from …. Neurotransmitters and hormones affecting satiety and hunger centers Several orexigenic (stimulating appetite) and anorexigenic (causing loss of appetite) peptides and neurotransmitters contribute to the regulation of food intake. Peripheral stimuli and inhibitors, release in anticipation of or in response to food intake, cross the blood-brain barrier (indicated by the broken red line) and activate the release and/or synthesis of central factors in the hypothalamus that either increase or decrease subsequent food intake. AA, amino acid; CART, cocaine- and amphetamine-regulated transcript; CCK, cholecystokinin; CRH, corticotropin-releasing hormone; FFA, free fatty acids; NE, norepinephrine; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; PYY, Peptide YY. Leptin - from the Greek leptos [thin] An appetite suppressing hormone released mainly from adipose tissue. More adipose tissue à more release of leptin If a person is subjected to starvation, adipocytes begin to shrink, as catabolic hormones mobilize triglycerides from adipocytes. This decrease causes a proportional reduction in leptin secretion from the shrinking cells. The decrease in leptin concentration removes the signal that normally inhibits appetite and speeds up metabolism Leptin & Neuropeptide Y Neuropeptide Y (NPY): Neuromodulator in the brain, increase food intake. Leptin inhibits NPY in a negative feedback pathway Within the ARC: One group of cell expresses neuropeptide Y (NPY); activation of these neurons causes increased food intake and decreased energy expenditure. The other group expresses proopiomelanocortin (POMC), which is a precursor for melanocortin peptides; activation of these neurons causes decreased food intake and increased energy expenditure. These neurons of ARC projects to Lateral hypothalamic area, paraventricular nucleus Leptin inhibits the NPY cells and stimulates the POMC cells in the ARC. CCK is a satiety signal mediated via the vagus, whereas ghrelin stimulates food intake by activating the NPY neurons in the ARC Neurons that produce agoutirelated protein (AGRP) and neuropeptide Y (NPY), increasing food intake and reducing energy expenditure. Pro-opiomelanocortin (POMC) neurons that release a α-MSH and CART, decreasing food intake and increasing energy expenditure; α-MSH stimulates melanocortin receptors (MCR-3 and MCR4) 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. LepR, leptin receptor; Y1R1, neuropeptide Y1 receptor; α-MSH, alpha-melanocyte–stimulating hormone; cocaine- and amphetamine-regulated transcript Outputs from the ARC that mediate alterations in feeding or energy expenditure include projections to the lateral hypothalamus, dorsomedial nucleus, and paraventricular nucleus, the brainstem and forebrain limbic system Main Hormones Affecting Food Intake Peptide YY (PYY) is secreted from the entire GI tract, but especially from the ileum and colon. Food intake stimulates release of PYY, with blood concentrations rising to peak levels 1 to 2 hours after ingesting a meal. Short-term effects on food intake Gastrointestinal filling inhibits feeding (very fast effect that limits the meal size) – Distension of GI tract (especially the stomach and the duodenum) inhibitory signals are transmitted mainly by vagus nerve to suppress the feeding centers – Sensation of hunger is also associated rhythmic contractions of the stomach and restlessness cholecystokinin (CCK), insulin, and ghrelin, act on a shorter time course The effect of oral receptors on hypothalamus Various “oral factors” related to feeding, such as chewing, salivation, swallowing, and tasting, “meter” the food as it passes through the mouth, and after a certain amount has passed, the hypothalamic feeding center becomes inhibited. the inhibition is considerably less intense and of shorter duration (usually lasting for only 20 to 40 minutes) compared to inhibition caused by gastrointestinal filling Intermediate- and Long-Term Regulation of Food Intake Effect of blood concentrations of glucose, amino acids, and lipids on hunger and feeding centers – e.g. hypoglycemia increases the firing rate of glucosesensitive neurons in the hunger center in the LHA, but decreases the firing rate of glucose-sensitive neurons in the satiety center in the VMN. – Hypoglycemia also activates orexin-containing neurons in the LHA. Feedback Signals From Adipose Tissue When the energy stores of the body fall below normal, the feeding centers of the hypothalamus and other areas of the brain become highly active, and the person exhibits increased hunger, as well as the behavior of searching for food. Conversely, when the energy stores (mainly the fat stores) are already abundant, the person usually loses the sensation of hunger and develops a state of satiety. Leptin act on a long-time course to maintain body weight Calories consumed (Energy intake) Resting metabolism Activity & Exercise consumed (Energy expenditure) What if the food intake regulation system fails? weight loss vs. weight gain Inanition (extreme weight loss) vs obesity Energy balance is regulated by integrating metabolism and eating behavior Energy balance is the homeostasis of energy in living systems. It is measured by the following equation: Energy intake = energy expenditure + storage Heat production (~50%) Work (~50%) Stability of body weight and composition over long periods requires that a person’s energy intake and energy expenditure be balanced Energy intake The most direct way to measure the energy content of food (energy intake) is by direct calorimetry Food is burned in an calorimeter and the heat released is measured. à Direct measure of the energy content (kcal) Bomb calorimeter kcal – is the amount of heat needed to rise the temperature of 1 l of water by 1°C Caloric content of foods Metabolic energy content of proteins and carbohydrates is 4kcal/g Fat – 9kcal/g 2g of fat, 7g of protein, and 38 g of carbonhydrate à 198kcal The metabolic energy content of food is slightly less – most foods cannot be fully digested and absorbed. Metabolic Processes At the cellular level, metabolic processes describe the mitochondrial conversion of fuel into the high-energy phosphates needed to support cellular activity. At the organism level, metabolic processes related with substrate utilization or substrate availability. Regulation of metabolic activity is tied strongly with the endocrine, gastrointestinal, and renal systems and, interacts with all other physiologic systems. Substrate availability is determined by intake, exchange with storage pools, metabolic consumption, and nonmetabolic loss The plasma concentration of the primary metabolic substrates (e.i. glucose and fatty acids) represents the balance between gastrointestinal absorption, exchange with storage pools, and loss through metabolic or non-metabolic routes. The first law of thermodynamics states that the total amount of energy in the universe is constant. Energy intake = energy expenditure + storage/growth Heat production Work Energy expenditure (Body metabolism) How can we measure the metabolic rate? Indirect calorimetry – measurement of O2 consumption or CO2 production the rate at which the body consumes oxygen as it metabolizes nutrients O2 consumption for different foods is relatively constant at a rate of 1 liter of oxygen consumed for each 4.5–5 kcal of energy released from the food being metabolized Metabolic rate (kcal/day) = LO2 consumed/day * kcal/LO2 Body metabolism Basal metabolic rate + metabolism tied to activity Individual’s lowest metabolic rate – Basal Metabolic Rate (BMR) Resting metabolic rate (RMR) -measured after a 12-hour of fasting in a person who is awake but resting RMR for a healthy, sedentary young man weighing 70 kg is approximately 2100 kcal (~30 kcal/kg body weight) Measurement of Basal metabolic rate (BMR) BMR is measured under standardized conditions, subject (1) has had a full night of restful sleep, (2) has been fasting for 12 hours, (3) is in a neutral thermal environment (4) has been resting physically for 1 hour, and (5) is free of psychic and physical stimuli. Hormonal regulation of energy balance Basal metabolic rate (BMR) is regulated by thyroid hormone and, alterations in thyroid hormone production alter wholebody metabolism. Thyroxine and epinephrine increase the cellular metabolic rate Insulin, glucagon, catecholamines, cortisol and growth hormone play major roles in energy regulation at times of acute energy needs, which occur during exercise, under conditions of stress, or in response to hypoglycemia. The major organs involved in fuel homeostasis are (1) the liver, which is normally the major producer of glucose; (2) the brain, which is the major utilizer of glucose (3) the muscle and adipose tissue, which respond to insulin and store energy in the form of glycogen and fat, respectively Cellular energetic is also tied to body core temperature. Increases in body core temperature increase metabolic activity in all tissues, and profound drops in body core temperature decrease the ability of all tissues to sustain metabolic activity. Energy intake = energy expenditure + storage Internal heat production work Energy stored in the body One way to estimate the total amount of energy stored in the body is a person’s body weight when energy intake exceeds energy output, a person gains weight. If energy use exceeds dietary energy input, the body make use of its energy stores and the person loses weight. BMI = weight in kg / [Height m]2 BMI is not a direct measure of adiposity and does not take into account the fact that some individuals have larger muscles BMI calculation does not distinguish between fat mass and muscle mass, however, and heavily muscled athletes, such as football players, may have a BMI that seems unhealthy. Fat mass index (fat mass / [height]2) is a better health indicator than BMI Body weight can be altered by changes in physical activity, composition of the diet, emotional states, stress, aging, pregnancy, and pharmacologic agents (e.g. atypical antipsychotics)