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Hormones Related to Hunger: Ghrelin
• Ghrelin:– Secreted by stomach– Acts on hypothalamus– Promotes hunger on short timescale (meal-to-meal)
• Empty stomachincreased 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 duodenumincreased 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 adiposeincrease leptininhibits 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
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
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
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)
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 actions of liver
Adipose tissue
Skeletal muscle
liver
Glycogen glycogenolysis glucose
glucoseLactic acid
amino acids
fatty acids
Gluconeogenisis
Gluconeogenisis glucose
Ketone bodies
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