Regulation of Hunger

Hormones Related to Hunger: Ghrelin Ghrelin: –Secreted by stomach –Acts on hypothalamus –Promotes hunger on short timescale (meal-to-meal) Empty stomach  increased ghrelin  promotes hunger Full stomach  decreased ghrelin  inhibits hunger

Hormones Related to Hunger: CCK Cholecystokinin (CCK): –Secreted by duodenum –Acts on hypothalamus –inhibits hunger on short, meal-to-meal, timescale Material in duodenum  increased ghrelin  supresses hunger Less material in duodenum  decreased ghrelin  promotes hunger

Hormones Related to Hunger: PYY Polypeptide YY (PYY): –Secreted by small intestine –Acts on hypothalamus –inhibits hunger on intermediate timescale Material in SI  PYY  suppresses hunger Less material in SI  PYY  promotes hunger

Hormones Related to Hunger: Leptin Adipokines (from adipose tissue) –A group of hormones released from adipose tissue –Evidence that some of them Inhibit ability of cells to uptake glucose and contribute to type II diabetes Leptin (an adipokine) –Amount of secretion is proportional to amount of adipose –Acts on hypothalamus –Supresses hunger on long term timescale Increased adipose  increase leptin  inhibits hunger Decreased adipose  decrease leptin  promotes hunger Evidence that individuals with hard to control obesity do not respond to leptin normally

Regulation of hunger on 3 time scales Red lines are inhibitory Green lines are stimulatory Intermediate term Short term

Hypothalamus Adipose Tissue, Leptin, Insulin, and appetite supression

Nutrient Absorption and Destination

1. Liver –Break down and synthesize (interconvert) most carbs, lipids, and amino acids/proteins –Stores glycogen –ONLY TISSUE THAT CAN RELEASE GLUCOSE* When glucose enters non-liver tissue it is phosphoylated preventing it from crossing back out across the PM Only the liver can de-phosphorylate 2. Adipose tissue –Stores lipids primarily as triglycerides –Can release lipids as fatty acids and glycerol *as far as we are concerned. five metabolic components/tissues

3. Skeletal muscle (close to half your body mass) –Creates substantial glycogen reserves –Proteins in myofibrils can be broken down as source of releasable amino acids –Uses mostly glucose and triglycerides for energy 4. Neural tissue--BRAIN –Requires glucose* and has high glucose demand –canNOT store energy reserves 5. Other tissues –Insignificant energy reserves –Variable use of carbs, lipids, and amino acids (and others) substrates. five metabolic components/tissues

Absorptive State 0-4 hrs after feeding Period of increase blood nutrient levels Period of increased nutrient availability Characterized by nutrient uptake by cells Cells use plasma nutrients as source of energy Cells generate nutrient stores from uptake of nutrients Promoted by insulin

Insulin Released from beta cells in pancrease Promotes cell uptake of nutrients from plasma Reduces blood glucose (lipids & amino acid) Production of glyocogen (glycogenisis) Stimulates adipocytes to synthesize triglycerides (with glucose) Stimulates protein synthesis Insulin release is stimulated by: High blood glucose levels High amino acids levels Digestive activity

Insulin release and action

Absorptive State Liver G.I. Tract (small intestines) Other cells blood

Fate of Nutrients: Absorptive State * Resting skeletal muscle uses triglycerides for ATP, but uptakes glucose and stores it as glycogen *

Interconversion of substrates (anabolism and catabolism): -- all major substrates can be broken down and used in aerobic respiration --major nutrients can be interconverted

ATP Adipose Tissue MuscleTissue Liver Interconversion of substrates: Common source organs/tissues

Post-Absorptive State >4 hrs after a meal Cells use own stored energy reserves Release of stored reserves into blood Formation of glucose from non-carbs (gluconeogenisis) Glucose sparing Ensures adequate blood glucose for the brain Promoted primarily by Glucagon –Also glucocorticoids, epinephrine, and other hormones

Post-Absorptive State & the Brain The brain is primarily dependent on glucose The brain does not store glucose or glycogen Brain is dependent on constant supply of blood glucose to function Many post-absorptive activities ensure brain has adequate glucose

Post-Absorptive State & the liver The liver is the only* organ that has cells which can release glucose The liver is the major metabolic organ that can interconvert major macromolecules The liver can release stored glucose into blood The liver can uptake non-carbs, convert them to glucose (gluconeogenisis), and then release that glucose

Stored Substrates 1-2 months of ATP ~ 4 hrs – overnight worth of ATP -- only liver can release glucose -- muscle glucose cannot be released Mostly in skeletal muscle Proteins (amino acids) 14.46% Mostly in adipose tissue

Glucagon Released by alpha cells in pancrease Breakdown of glycogen (glycogenolysis) in liver and relase of glucose into blood Stimulates gluconeogenisis in liver and release of glucose into blood Stimulates adipocytes to release lipids Blood fatty acid levels rise Glucagon release is stimulated by low blood sugar

Glucocorticoids (e.g. cortisol) Released from the andrenal cortex Increase glucose synthesis in liver (gluconeogenisis) Causes adipose cells to release fatty acids into blood Promotes protein breakdown and amino acid release into blood Inhibits glucose use by organs/tissues other than the brain (spares glucose for brain) Causes other tissues to metabolize fatty acids and proteins rather than glucose for their own needs to “spare” glucose for the brain. Also anti-inflammatory and inhibits WBC, release of histimine and reduce the movement of phagocytes to the site generally reducing inflammation but slowing the healing and increasing risk of infection. Increased levels released in response to stress (e.g., fasting and physical activity)

Glucocorticoids From adrenal cortex Catabolic –E.g. cortisol

CRH ACTH Glucocorticoids Adrenal cortex hypothalamus Glucocorticoid release Hypothalamus releases CRH (corticotropin releasing hormone) which travels to anterior pituitary. Anterior pituitary responds by releasing ACTH(adrenocorticotropic hormone, from anterior pituitary) ACTH stimulates adrenal cortex to lease glucocorticoids into blood. Glucocorticoids inhibit CRH release (classic negative feedback).

Post-absorptive State Liver G.I. Tract (small intestines) blood Other cellsBrain

Post Absorptive Substrate Fate

Post-absorptive actions of liver Adipose tissue Skeletal muscle liver Glycogen  glycogenolysis glucose Lactic acid amino acids fatty acids Gluconeogenisis glucose Ketone bodies

Insulin, Glucagon and Blood Sugar

Insulin and Glucagon: action of liver and adipose cells

Gluconeogenesis Occurs when amino acids or other non-carbos are converted to Keto acids, then pyruvate, then glucose 5-46

Uses of Different Energy Sources Different cells have different preferred energy substrates Brain uses glucose as its major source of energy –One goal of metabolic regulation is to ensure adequate blood glucose levels to supply brain with glucose 5-48

Gluconeogensis: non-carb  glucose Gylcogeniss: glucose  glycogen Glycogenolysis: glycogen  glucose Lipogenisis: making lipids/triglycerides Lipolysis: triglycerides  fatty acids + glycerol Transmamination: intercoverting amino acids

Blood Glucose Levels