glycogen are sufficient for brief period (<24hr) of fasting – mostly used for emergencies (vigorous exercise)
Liver can release glucose into blood via Glucose-6-Pase; Muscle must consume its own glycogen
Muscle protein
is another possible source but is unfavorable since you would in effect digest your muscles
Adipose
TG’s provide the major storage form of readily-available energy – provides FFA’s to liver which makes ketones that are necessary for prolonged starvation
Fuel homeostasis principally regulates the needs of brain and muscle (major consumers of fuel)
brain – glucose exclusively (120g/d) until prolonged starvation (~2 days) then switches to ketones (fuel sparing)
Metabolic Changes during Starvation
Mechanisms of Protein Conservation
Muscle protein breakdown during starvation provides liver (for gluconeogenesis) and kidney (for ammoniagenesis)
During 1st days of starvation, amino acids (Ala, Gln) are synthesized and released from muscle
Ala goes to liver for gluconeogenesis
Gln goes to kidney for ammoniagenesis (also yields glucose); or goes to gut and converted to Ala which goes to liver
As starvation progresses, ammoniagenesis required to maintain acid-base homeostasis rises in kidney (due to increased FFA’s and circulating ketones) which secondarily yields more glucose thus kidney becomes major source of gluconeogen
By 3 days starvation, brain begins utilizing ketones and skeletal muscle relies on ketones for 50% of its energy
The switch from glucose to ketone usage aids in reducing the rate of muscle protein degradation needed for gluconeogenesis – if this did not occur, the body would lose >˝ of its muscle protein within 17 days leading to death
By 24 days starvation, ketone synthesis, nitrogen excretion, and gluconeogen (from lactate, glycerol, Gln) reach a steady state allowing starvation to persist for 2 – 3 months
Ketone Body Metabolism
Increased availability of FFA’s during starvation provides liver with increased levels of acetyl CoA and eventually exceeds the oxidative capacity of the liver, thus acetyl CoA is shifted from the TCA cycle towards ketone synthesis
Acetyl CoA is made into HMG-CoA via HMG-CoA Synthase (rate-limiting enzyme – only found in liver); HMG-CoA is then made into acetoacetate, b-hydroxybutyrate, and acetone (minor) and released into blood since liver cannot utilize them
Ketones are used by skeletal and cardiac muscle, the renal cortex, and other tissues (brain only uses during starvation)
Role of the Kidney
Kidney, like liver, possesses the complete enzymatic apparatus for gluconeogenesis
During brief periods of starvation, kidney’s rate of gluconeogenesis is 10% to that of the liver
During prolonged starvation, ammoniagenesis increases due to increased acid load which accelerates its rate of gluconeo
The principle gluconeogenic substrate is Gln which also provides the free NH3 (used to titrate excess H+ ions)
Hormonal Control During Starvation
Insulin levels decrease (aids FA mobilization, gluconeogenesis and ketone production)
Growth hormone increases (stimulates lypolysis) with a reduction in thyroid hormone (major energy conserving adaptation by decreasing basal metabolic rate and limiting muscle protein breakdown)
Glucagon (stimulates gluconeogenesis) Ý , then returns to postabsorptive levels concurrent with reduced glucose demand
The Five Phases of Glucose Homeostasis
PHASE I (Absorptive)
blood glucose derived from exogenous CHO; insulin and glucose
Ý , glucagon ß
excess glucose converted to liver and muscle glycogen and lipid
PHASE II (post-absorptive and early starvation)
glucagon, glucose, insulin return to basal levels; liver glycogen
Þ glucose
brain is major user of glucose
oxidation of glucose is inhibited in muscle and adipsose tissue at the PDC (pyruvate-DH complex), causing increased release of lactate, pyruvate, and alanine for gluconeogenesis
PHASE III and early PHASE IV
hepatic and renal gluconeogenesis;
ß insulin and Ý glucagon
increased released of gluconeogenic precursors; great demand for gluconeogenesis
ketones are primary energy source for brain; muscle consumes FA and ketones
Refeeding and Metabolism After Injury
Refeeding after starvation should be monitored closely or the marked increase in amino acids could lead to an increased rate of deamination that may exceed the urea cycle leading to toxic levels of ammonia
Metabolic response to injury is similar to starvation except there is an elevation in plasma glucose rather than decrease
Obesity Gene
Lipostat (in mouse) is sent to brain
Þ tells brain we are above set body weight Þ brain decreases appetite
Leptin (in human) inhibits insulin and signals the brain to increase sympathetic
Þ causes increase in energy expenditure
adipocyte
Þ leptin Þ hypothalamus Þ change energy expenditure
In obese people, leptin is increased, but is not having the effect it should (brain is not correcting things)
We can make a hormone which activates the leptin receptor in the brain (brain regulation hormone)