Starvation response in animals (including humans) is a set of adaptive biochemical and physiological changes, triggered by lack of food or extreme weight loss, in which the body seeks to conserve energy by reducing metabolic rate and/or non-resting energy expenditure to prolong survival and preserve body fat and lean mass.
Ordinarily, the body responds to reduced energy intake by firstly exhausting the contents of the digestive tract along with glycogen reserves present in both muscle and liver cells via glycogenolysis.
[3] The magnitude and composition of the starvation response (i.e. metabolic adaptation) was estimated in a study of 8 individuals living in isolation in Biosphere 2 for two years.
During their isolation, they gradually lost an average of 15% (range: 9–24%) of their body weight due to harsh conditions.
On average, the starvation response of the individuals after isolation was a 750-kilojoule (180-kilocalorie) reduction in daily total energy expenditure.
Glycogen is a readily-accessible storage form of glucose, stored in notable quantities in the liver and skeletal muscle.
Ketone bodies are short-chain derivatives of the free fatty acids mentioned in the previous paragraph, and can cross the blood–brain barrier, meaning they can be used by the brain as an alternative metabolic fuel.
Fatty acids can be used directly as an energy source by most tissues in the body, but are themselves too ionized to cross the blood–brain barrier[contradictory].
After 2 or 3 days of fasting, the liver begins to synthesize ketone bodies from precursors obtained from fatty acid breakdown.
Thus, after periods of starvation, the loss of body protein affects the function of important organs, and death results, even if there are still fat reserves left unused.
The body also engages in gluconeogenesis to convert glycerol and glucogenic amino acids into glucose for metabolism.
Epinephrine precipitates lipolysis by activating protein kinase A, which phosphorylates hormone sensitive lipase (HSL) and perilipin.
The resulting acetyl-CoA enters the TCA cycle and undergoes oxidative phosphorylation to produce ATP.
The resulting ketone bodies, acetoacetate and β-hydroxybutyrate, are amphipathic and can be transported into the brain (and muscles) and broken down into acetyl-CoA for use in the TCA cycle.
This process distorts the structure of the cells,[15] and a common cause of death in starvation is due to diaphragm failure from prolonged autophagy.
Starvation contributes to antibiotic tolerance during infection, as nutrients become limited when they are sequestered by host defenses and consumed by proliferating bacteria.
[16][17] One of the most important causes of starvation induced tolerance in vivo is biofilm growth, which occurs in many chronic infections.
[21] Biofilm bacteria shows extreme tolerance to almost all antibiotic classes, and supplying limiting substrates can restore sensitivity.