NUTR 470 1st Edition Lecture 18-Nutritional Control of Systemic Metabolic Homeostasis-At the cellular level• Lipogenesis, lipolysis, fatty acid oxidation, and ketogenesis are cooperatively regulated.• Four major glucose fluxes are cooperatively regulated (in liver cells).-At the whole body level• Multiple tissues/organs are participating in the coordinated regulation to achieve whole body fuel homeostasis.-Integrative Regulation of Fuel Homeostasis• Under physiological conditions, feeding and fasting are the primary conditions that trigger the integrative regulation.-Feeding• Digestion and absorption of food result in elevations in the levels of glucose.• Glucose, at high levels, stimulates the secretion of insulin and decreases the secretion of glucagon.• Digestion and absorption of food also result in elevations in the levels of circulating lipids.• Since glucose is in excess, lipid metabolism runs toward storage. -Fasting• Glucose levels return to or drop slightly below the normal range.• The reduction in glucose levels stimulates the secretion of glucagon and decreases the secretion of insulin.• When glucose is not sufficient, lipid is mobilized from storage to provide a fuel.• Fat tissue is the major source providing free fatty acids. -Stimuli• Nervous, exciting, anxious, stress• FightingThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.• Emerging reactions-Stimuli increase the levels of epinephrine.-Stressors• In response to acute stress, the pituitary-adrenal axis is participating in the integrative regulation.-Injury, damage, trauma-Fever, infection-Angry • Stressors cause an increase in the levels of glucagon, glucocorticoid, and other hormones.-Changes in the levels of nutritional and hormonal factors are responsible for the integrative regulation of glucose and lipid metabolism.• Promoting glucose and lipid storage-Glucose, insulin• Promoting glucose production-Glucagon, epinephrine, glucocorticoid• Promoting lipid mobilization/utilization-Glucagon, epinephrine-Nutritional and hormonal factors are integrated as changes in the activities of enzymes that are related to glucose metabolism. • Promoting glucose utilization/storage -HK/GK, 6PFK1, GS • Promoting lipid synthesis/storage -ACC, FAS• Promoting glucose production-PEPCK, FBPase, G6Pase, GP • Promoting lipolysis and FA oxidation/ketogenesis-HSL, CPT1, HMG-CoA synthase-The integrative regulation of glucose homeostasis is achieved through coordinating glucose metabolic fluxes. • Promoting glucose utilization/storage-Glycolysis and glucogenesis• Promoting glucose production-Gluconeogenesis and glycogenolysis-The integrative regulation of glucose homeostasis is achieved through coordinating lipid metabolism.• Promoting lipid synthesis/storage-Lipogenesis• Promoting lipid mobilization/utilization-Lipolysis, FA oxidation, ketogenesis-Coordinated Regulation of Energy Homeostasis• Key points for coordination-When glucose is in excess, there should be an increase in glucose utilization/storage (glycolysis/glycogenesis).-When glucose is not enough, there should be an increase in gluconeogenesis/glycogenolysis in the liver to produce glucose.-Promoting glucose production and lipolysis and fatty acid oxidation-When glucose is in excess, glucose is first stored as glycogen, and then as fat.-When glucose is not enough, fuels are provided first from glycogen breakdown and gluconeogenesis and then from lipolysis, fatty acid oxidation, and ketogenesis. -Glucose, at high levels, stimulates the secretion of insulin and inhibits the secretion of glucagon – favoring energy storage-Stress and emerging reactions (sympathetic excitement) stimulate the secretion of epinephrine – favoring energy production-Coordinated Regulation of Energy-Summary• Glucose metabolic pathways• Integrative regulation• Regulation of a single pathway• Roles of nutritional, hormonal signalsRegulation of two or more