STEPTRACKERBIOCHEMISTRY + PHYSIOLOGY | METABOLISM PRINCIPLES | HIGH-YIELD REVIEW

Fed, Fasting & Starvation States

What the body burns hour by hour after a meal — and which tissues can switch fuels while the brain and red cells cannot.

FOCUS ON
Fed (insulin): glycolysis, glycogen and fat synthesis. Fasting, day 1–3 (glucagon): glycogenolysis first (liver glycogen lasts ~1 day), then gluconeogenesis from amino acids, lactate, glycerol. Starvation > 3 days: ketone bodies fuel the brain, muscle protein is spared; once fat stores are gone, protein breakdown → organ failure. RBCs use only glucose (no mitochondria); the liver can't use ketones (no thiophorase).
STATE · TISSUE
MAIN FUEL / PROCESS
HORMONES
CLUE
Fed state
0–4 h
Glycolysis, glycogenesis, lipogenesis, protein synthesis
↑ Insulin
GLUT4 in muscle/fat recruited by insulin
Early fasting
4 h – 1 day
Hepatic glycogenolysis, start of gluconeogenesis; lipolysis begins
↑ Glucagon, ↑ epinephrine
Liver glycogen exhausted in ~24 h
Fasting
1–3 days
Gluconeogenesis (alanine, lactate, glycerol, propionate), β-oxidation in liver and muscle
Glucagon, cortisol
Muscle protein broken down for substrates
Starvation
> 3 days
Fat stores → FFAs; liver makes ketones → brain adapts (up to ~⅔ of its fuel); protein spared
↓↓ Insulin
Survival depends on fat reserves (~1–3 months)
Brain
Glucose; ketones in prolonged fasting; not fatty acids (don't cross BBB well)
Insulin-independent (GLUT1/3)
Hypoglycemia → confusion, seizures
Red blood cells
Glucose only, by anaerobic glycolysis → lactate
GLUT1
No mitochondria → can't use ketones or FAs
Liver
Fatty acids for its own energy; makes glucose and ketones for others
GLUT2
Can't use ketones (lacks succinyl-CoA:acetoacetate transferase)
Skeletal muscle
Glucose and FAs at rest; fatty acids, ketones in fasting; creatine phosphate and glycogen in bursts
GLUT4 (insulin)
Muscle glycogen serves muscle only (no glucose-6-phosphatase)
Heart
Fatty acids (main), ketones, lactate, glucose
—
Highly oxidative
Adipose
Stores triglyceride (fed); hormone-sensitive lipase releases FFAs + glycerol (fasting)
Insulin inhibits HSL; epinephrine, glucagon activate
Glycerol → liver gluconeogenesis
Insulin-independent glucose uptake
Brain, RBCs, liver, kidney, intestine, cornea, lens, placenta, islet β cells
GLUT1, 2, 3
Sites of sorbitol damage in diabetes (8.06)

Mechanism — fuel source by time since last meal

MealDietary glucose
→
HoursLiver glycogen
→
1–3 daysGluconeogenesis (muscle protein)
→
> 3 daysKetones, protein spared
→
Fat goneProtein breakdown, death

Which tissue can use which fuel?

TISSUE
GLUCOSE
FATTY ACIDS
KETONES
Brain
Yes
No
Yes (starvation)
RBC
Yes
No
No
Liver
Yes
Yes
No (makes them)
Muscle, heart
Yes
Yes
Yes

How it's tested

COMMON CONFUSIONEven-chain fatty acids cannot make net glucose (acetyl-CoA is lost as CO₂); glycerol and odd-chain fatty acids (via propionyl-CoA) can.
THE TRAPMuscle glycogen can't raise blood glucose — muscle lacks glucose-6-phosphatase.
YOUR APPROACHTime since last meal → dominant hormone → main fuel source → which tissues depend on it.

If you see… think…

Main glucose source 12 h after a meal → hepatic glycogenolysis
Main glucose source on day 2 of fasting → gluconeogenesis
Brain fuel after a week of starvation → ketone bodies
Cell type using only glucose → RBC
Organ that makes ketones but cannot use them → liver
Gluconeogenic substrate from adipose → glycerol
Fatty acids that can yield glucose → odd-chain (propionyl-CoA)
Insulin-dependent glucose transporter → GLUT4 (muscle, fat)
Lipase activated by epinephrine, inhibited by insulin → hormone-sensitive lipase
Main fuel of the heart → fatty acids