Energy Balance & Temperature Regulation PDF

Energy Balance & Temperature Regulation Andrea C. Gore, PhD Professor, Division of Pharmacology and Toxicology [email protected] 1 Learning Objectives By the end of this lecture you will learn about and understand: Principles of energy balance. Role of the hypothalamus in energy balance...

Energy Balance & Temperature Regulation Andrea C. Gore, PhD Professor, Division of Pharmacology and Toxicology [email protected] 1 Learning Objectives By the end of this lecture you will learn about and understand: Principles of energy balance. Role of the hypothalamus in energy balance and feeding behavior. Hypothalamic and peripheral peptides/hormones that control energy balance. The role of the hypothalamus in temperature homeostasis. 2 Energy Balance Cells require energy to function. Energy input: Ingested food provides nutrients that provide energy (ATP). Energy output (expenditure): “work” (mechanical movement); unconscious activities (respiration, circulation, cellular metabolism). When we eat, 75% of energy from nutrients is converted to heat (which is lost, or used to maintain body temperature), and 25% can be used as an energy source in the body. 3 Metabolic, Basal Metabolic Rate Metabolic rate = energy expenditure/unit time, expressed as kcal/hr (in humans, we refer to this as Calories). [A calorie is the basic unit of heat energy = amount of heat necessary to raise the temperature of 1g of H2O by 1oC; a Calorie = 1000 calories] Basal Metabolic Rate = minimal waking rate of internal energy expenditure while the body is idle. 4 Measuring basal metabolic rate 1. 2. 3. 4. Person should be at physical rest Person should be at mental rest (stress/anxiety can alter BMR) The measurement should be performed at a comfortable temperature – avoid shivering Person should not have eaten within 12 hours to avoid dietinduced thermogenesis 5 Energy Balance states ¡Neutral energy balance (input=output) ¡Positive energy balance (input>output) ¡Negative energy balance (output>input) Figure courtesy of Kristy Townsend Under what condition would you lose weight? 6 The hypothalamus integrates energy balance signals Short term regulation of energy balance Amount, composition of food Nutrient absorption & assimilation Satiety, sense of fullness Other Vocabulary: Orexigenic: stimulates appetite Anorexigenic: inhibits appetite 7 Hypothalamus and gut-brain axis The gut-brain axis: - neural and hormonal signals Ø Afferent vagal fibers convey distention in response to pressure receptors in the gut Ø These hormones circulate through the blood. Ø Receptors for these hormones are localized in the hypothalamus and other brain areas such as brainstem Hormone Where made What it does GLP-1 (glucagon-like peptide 1) Intestinal epithelial L cells Incretin, Inhibits appetite (also stimulates insulin secretion CCK (cholecystokinin) Intestinal cells Signals satiety in brainstem and hypothalamus PYY3-36 (peptide YY) Intestine Signals satiety when intestine begins to fill Insulin Pancreatic β-cells Inhibits appetite in response to increasing blood glucose Ghrelin Stomach Stimulates appetite 8 Hypothalamic control of energy balance Ø Groups of neurons have receptors for gut peptides that convey peripheral information about satiety. Ø These neurons produce neuropeptides that stimulate or inhibit appetite. This is responsible for the central control of energy balance. Region Transmitter Function and description Arcuate nucleus (ARC) -Neuropeptide Y (NPY) -Agouti-related protein (AgRP) Increase appetite & food intake. These two neuropeptides are coexpressed in the same neurons. ARC -Melanocortins (α, β, γmelanocyte-stimulating hormone (MSH) -Cocaine-amphetamine related transcript (CART) Melanocortins are a family of neuropeptides derived from proopiomelanocortin (POMC) gene. CART is co-expressed in some of these neurons. Both suppress appetite & food intake. Lateral hypothalamic area (LHA) -Orexins Stimulate appetite Paraventricular nucleus (PVN) -Corticotropin releasing hormone (CRH, CRF) Inhibit appetite (note: also a stress hormone in the HPA axis) 9 Leptin’s role in the hypothalamic control of energy balance Hormone Where made What it does Leptin Adipocytes (fat cells) Leptin is an adipokine (fat hormone) released in proportion to triglyceride storage (long-term) and feeding (short-term). It binds to leptin receptors on cells in the hypothalamus where it acts as a satiety factor that inhibits appetite. 10 Hypothalamic control of energy balance Meal + ↑ Fat and other nutrients in duodenum ↑ blood glucose and other nutrients ↑ Ghrelin (from stomach before meal) ↑ PPY3-36 (from intestine during meal) Initiates meal Terminates meal + Brainstem ↑ Leptin _ _ + + _ ARC NPY secreting neuron POMC secreting neuron Melanocortins/ CART Neuropeptide Y/ AGRP + Vagal nerve afferents + ↑ Body fat stores ↑ Insulin Stomach distension ↑ Cholecystokinin + _ Lateral hypothalamus neurons + Orexins Appetite stimulating pathway Signals satiety _ + _ _ + Paraventricular nucleus neurons Corticotropinreleasing hormone Food intake _ Appetite suppressing pathway Temperature Regulation Normal body temperature varies among individuals and throughout the day – ranges from 96ºF in the morning to 99.9ºF in the evening Overall average is 98.2ºF Temperature ranges by organ Core body temperature – temperature within the abdominal and thoracic organs, the CNS, and the skeletal muscles is closer to 100ºF 12 Temperature Regulation Changes in body temperature in either direction alters cellular activity Increase: Speeds up cellular chemical reactions Overheating is more serious than cooling Nerve malfunction, irreversible protein denaturation Internal body temperature 106ºF → convulsions 110ºF → upper limit compatible with life Decrease: Slows down cellular reactions Pronounced, prolonged fall in body temperature slows metabolism to fatal level 13 Temperature Regulation Sites for monitoring body temperature Oral and axillary temperatures are comparable Rectal temperature averages about 1ºF higher Eardrum scan (similar to oral) Forehead scan – temporal scanner (similar to rectal temp). Normal variations in core temperature Circadian rhythms of temperature normally varies about 1.8ºF during the day Monthly rhythm in core temperature - menstrual cycle Increases during exercise due to muscle heat Varies slightly with exposure to extremes of temperature Core temperature decreases with aging. 14 Hypothalamic Control of Thermoregulation The hypothalamus is the body’s thermostat Contains & monitors thermoreceptors Central thermoreceptors – monitor core temperature Located in hypothalamus, other parts of CNS, and abdominal organs Peripheral thermoreceptors – monitor periphery Monitor skin temperature throughout body and transmit information to hypothalamus Hypothalamic centers involved in temperature regulation: Posterior region - Activated by cold Anterior region - Activated by warmth 15 Infection or inflammation Fever: Elevation in body temperature as result of infection or inflammation. Pyrogens: ¡ Exogenous pyrogens: e.g. bacteria lipopolysaccharide cause endogenous pyrogen release. ¡ Endogenous pyrogens: cytokines, eg: interleukins (IL-1, IL-6,) and tumor necrosis factors (TNFs) released by macrophages/microglia to fight infection; they also increase thermostat setting Immune cells Pyrogens Hypothalamus: Prostaglandins éthermostat set-point Hypothalamus ¡ Prostaglandins: PGE2 release can be blocked by aspirin. ¡ Hypothalamic thermostat éHeat production, êheat loss § A new, higher temperature set-point. Fever is a highly regulated response (not a loss of thermoregulation). New set-point èFever 16 Hyperthermia Elevation in body temperature above normal range, in conditions other than fever Causes: Exercise-induced Exposure to severe heat stress Pathological Hyperthyroidism Oversecretion of epinephrine (adrenal medulla) Hypothalamic malfunction (brain lesion) 17 Learning Objectives By the end of this lecture you will learn about and understand: Principles of energy balance. Role of the hypothalamus in energy balance and feeding behavior. Hypothalamic and peripheral peptides/hormones that control energy balance. The role of the hypothalamus in temperature homeostasis. 18