Summary
FUEL HOMEOSTASIS
what is the need for fuel homeostasis
constant requirement of tissues for energy (especially CNS for glucose)
but sporadic food intake
plasma glucose maintained 5-10mM/l (x18 to get to mg/dl) - fasting 4-5.4
what are the major organs involved in fuel homeostasis
liver = major glycogen store (short term, 1000cal) and fatty acid b-
oxidation for ketones
adipose = triacylglycerol (long term, largest store as low water content
9cal/g)
muscle = major consumer, some glycogen stores but only local use,
protein breakdown
small intestine = most digestion and absorption
describe the absorptive state and fates of each macro
~3hrs after meal (food in GI tract)
glucose (sucrose > gluc + fruc) + AAs in GI tract into enterocytes epithelia
via glucose/na symporter SGLT1, fructose via GLUT5 > into blood via
GLUT2 > hepatic portal vein > liver
TAG through lymphatics to adipose
anabolic
1. glucose
liver - converted to glycogen then excess to a-glycerol phosphate and FAs
> TAG > packed into VLDL > to adipose > FA uptaken
muscle - oxidise for energy and stored as glycogen
adipose - excess to a-glycerol phosphate and FAs > TAG
Summary 1
, tissues - use for energy (GLUT1 RBC, BBB; GLUT2 beta cells, kidney, liver,
intestine; GLUT3 brain, neurones, placenta; GLUT4 muscle, adipocyte)
2. AAs
liver - (minority) deaminated to keto acids + urea > keto acids enter
TCA/FA synthesis (not converted to glucose until post absorptive)
muscle/organs - protein synthesis, replenish pools
excess converted to fat
3. TAG
adipose - FA uptaken from VLDL/chylomicrons > TAG synthesis with aGP
(from glucose) > storage
organs - oxidised for energy
describe the post-absorptive state
default - empty GI tract, anabolism stops and catabolism starts to generate
glucose from stores
glycogenolysis (first response)
liver - first response (most accessible) to release glucose into blood, rapid
but short term
muscle - more stores but lacks glucose 6 phosphotase enzyme so can’t
directly make glucose > G6P glycolysis to lactate/pyruvate > converted to
glucose in liver gluconeogenesis
protein catabolism (main source after few hrs)
skeletal muscle degradation > AAs > converted to keto acids then glucose
in liver > released to circulation
lipolysis (after several hrs)
TAG lysis in adipose > FA and glycerol > glycerol to glucose and FA
oxidation in liver
glucose sparing: tissues reduce glucose use and rely on FA oxidation to
spare for CNS
Summary 2
, tissues: FA from lipolysis > acetylcoA > enter TCA > oxidised for energy
liver ketogenesis: FA > acetylcoA > ketones > released for CNS
gluconeogenesis from lactate/pyruvate, glycerol, AAs (kidneys and liver)
the hormones involved in absorptive state
inc blood glucose > insulin release - acute rapid phase (mins) then
sustained second phase
also inhibits glucagon release
insulin effects = anabolic, inc uptake/utilisation/storage of glucose (see
below) > dec blood glucose
hormones involved in post-absorptive state
dec blood glucose > stimulates glucagon release and inhibits insulin
release
still basal insulin secretion ~ 0.5-1.5units/hr
glucagon main effects (below)
cortisol, GH, TH all permissive for catabolism
neuronal control of fuel homeostasis
1. dec plasma glucose
2. glucose receptors in CNS activated (reflex)
inc SNS innervation of islets > inhibits insulin release and stimulate
glucagon release
inc activation of adrenal medulla > adrenaline secretion into blood > inc
glycogenolysis in skeletal muscle, inc lipolysis in adipose, inc
glycogenolysis/gluconeogenesis in liver, inc insulin resistance/inhibited
secretion
3. inc activity of SNS nerves to adipose and liver > inc lipolysis in adipose
and glycogenolysis/gluconeogenesis in liver (no innervation to muscle)
4. inc blood glucose, FA, glycerol
responses to starvation (no insulin)
Summary 3
FUEL HOMEOSTASIS
what is the need for fuel homeostasis
constant requirement of tissues for energy (especially CNS for glucose)
but sporadic food intake
plasma glucose maintained 5-10mM/l (x18 to get to mg/dl) - fasting 4-5.4
what are the major organs involved in fuel homeostasis
liver = major glycogen store (short term, 1000cal) and fatty acid b-
oxidation for ketones
adipose = triacylglycerol (long term, largest store as low water content
9cal/g)
muscle = major consumer, some glycogen stores but only local use,
protein breakdown
small intestine = most digestion and absorption
describe the absorptive state and fates of each macro
~3hrs after meal (food in GI tract)
glucose (sucrose > gluc + fruc) + AAs in GI tract into enterocytes epithelia
via glucose/na symporter SGLT1, fructose via GLUT5 > into blood via
GLUT2 > hepatic portal vein > liver
TAG through lymphatics to adipose
anabolic
1. glucose
liver - converted to glycogen then excess to a-glycerol phosphate and FAs
> TAG > packed into VLDL > to adipose > FA uptaken
muscle - oxidise for energy and stored as glycogen
adipose - excess to a-glycerol phosphate and FAs > TAG
Summary 1
, tissues - use for energy (GLUT1 RBC, BBB; GLUT2 beta cells, kidney, liver,
intestine; GLUT3 brain, neurones, placenta; GLUT4 muscle, adipocyte)
2. AAs
liver - (minority) deaminated to keto acids + urea > keto acids enter
TCA/FA synthesis (not converted to glucose until post absorptive)
muscle/organs - protein synthesis, replenish pools
excess converted to fat
3. TAG
adipose - FA uptaken from VLDL/chylomicrons > TAG synthesis with aGP
(from glucose) > storage
organs - oxidised for energy
describe the post-absorptive state
default - empty GI tract, anabolism stops and catabolism starts to generate
glucose from stores
glycogenolysis (first response)
liver - first response (most accessible) to release glucose into blood, rapid
but short term
muscle - more stores but lacks glucose 6 phosphotase enzyme so can’t
directly make glucose > G6P glycolysis to lactate/pyruvate > converted to
glucose in liver gluconeogenesis
protein catabolism (main source after few hrs)
skeletal muscle degradation > AAs > converted to keto acids then glucose
in liver > released to circulation
lipolysis (after several hrs)
TAG lysis in adipose > FA and glycerol > glycerol to glucose and FA
oxidation in liver
glucose sparing: tissues reduce glucose use and rely on FA oxidation to
spare for CNS
Summary 2
, tissues: FA from lipolysis > acetylcoA > enter TCA > oxidised for energy
liver ketogenesis: FA > acetylcoA > ketones > released for CNS
gluconeogenesis from lactate/pyruvate, glycerol, AAs (kidneys and liver)
the hormones involved in absorptive state
inc blood glucose > insulin release - acute rapid phase (mins) then
sustained second phase
also inhibits glucagon release
insulin effects = anabolic, inc uptake/utilisation/storage of glucose (see
below) > dec blood glucose
hormones involved in post-absorptive state
dec blood glucose > stimulates glucagon release and inhibits insulin
release
still basal insulin secretion ~ 0.5-1.5units/hr
glucagon main effects (below)
cortisol, GH, TH all permissive for catabolism
neuronal control of fuel homeostasis
1. dec plasma glucose
2. glucose receptors in CNS activated (reflex)
inc SNS innervation of islets > inhibits insulin release and stimulate
glucagon release
inc activation of adrenal medulla > adrenaline secretion into blood > inc
glycogenolysis in skeletal muscle, inc lipolysis in adipose, inc
glycogenolysis/gluconeogenesis in liver, inc insulin resistance/inhibited
secretion
3. inc activity of SNS nerves to adipose and liver > inc lipolysis in adipose
and glycogenolysis/gluconeogenesis in liver (no innervation to muscle)
4. inc blood glucose, FA, glycerol
responses to starvation (no insulin)
Summary 3
