Starvation response

Source: Wikipedia, the free encyclopedia.

Starvation response in animals (including humans) is a set of adaptive

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.[1]

Equivalent or closely related terms include famine response, starvation mode, famine mode, starvation resistance, starvation tolerance, adapted starvation, adaptive thermogenesis, fat adaptation, and metabolic adaptation.

In humans

Ordinarily, the body responds to reduced energy intake by burning fat reserves and consuming muscle and other tissues. Specifically, the body burns fat after first exhausting the contents of the digestive tract along with glycogen reserves stored in liver cells via glycogenolysis, and after significant protein loss.[2] After prolonged periods of starvation, the body uses the proteins within muscle tissue as a fuel source, which results in muscle mass loss.[3]

Magnitude and composition

The magnitude and composition of the starvation response (i.e. metabolic adaptation) was estimated in a study of 8 individuals living in isolation in

fat mass. An additional 270 kJ (65 kcal) was explained by a reduction in fidgeting. The remaining 230 kJ (55 kcal) was statistically insignificant.[4]

General

The energetic requirements of a body are composed of the

fatty acids
stored in adipose tissue.

Because of the blood–brain barrier, getting nutrients to the human brain is especially dependent on molecules that can pass this barrier. The brain itself consumes about 18% of the basal metabolic rate: on a total daily intake of 7,500 kJ (1,800 kcal), this equates to 1,360 kJ (324 kcal), or about 80 g of glucose. About 25% of total body glucose consumption occurs in the brain.

Glucose can be obtained directly from dietary sugars and by the breakdown of other

carbohydrates. In the absence of dietary sugars and carbohydrates, glucose is obtained from the breakdown of stored glycogen. Glycogen is a readily-accessible storage form of glucose, stored in notable quantities in the liver and skeletal muscle.[5]

When the glycogen reserve is depleted, glucose can be obtained from the breakdown of fats from adipose tissue. Fats are broken down into glycerol and free fatty acids, with the glycerol being turned into glucose in the liver via the gluconeogenesis pathway.

When even the glucose made from glycerol reserves start declining, the liver starts producing

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
].

Timeline

After the exhaustion of the glycogen reserve, and for the next 2–3 days, fatty acids are the principal metabolic fuel. At first, the brain continues to use glucose, because if a non-brain tissue is using fatty acids as its metabolic fuel, the use of glucose in the same tissue is switched off. Thus, when fatty acids are being broken down for energy, all of the remaining glucose is made available for use by the brain.

After 2 or 3 days of fasting, the liver begins to synthesize ketone bodies from precursors obtained from fatty acid breakdown. The brain uses these ketone bodies as fuel, thus cutting its requirement for glucose. After fasting for 3 days, the brain gets 30% of its energy from ketone bodies. After 4 days, this goes up to 75%.[6]

Thus, the production of ketone bodies cuts the brain's glucose requirement from 80 g per day to about 30 g per day. Of the remaining 30 g requirement, 20 g per day can be produced by the liver from glycerol (itself a product of fat breakdown). This still leaves a deficit of about 10 g of glucose per day that must come from some other source. This deficit is supplied via gluconeogenesis from amino acids from proteolysis of body proteins.

After several days of fasting, all cells in the body begin to break down

amino acids into the bloodstream, which can be converted into glucose by the liver. Since much of the human body's muscle mass is protein, this phenomenon is responsible for the wasting away of muscle mass seen in starvation
.

However, the body can selectively decide which cells break down protein and which do not.[citation needed] About 2–3 g of protein must be broken down to synthesize 1 g of glucose; about 20–30 g of protein is broken down each day to make 10 g of glucose to keep the brain alive. However, to conserve protein, this number may decrease the longer the fasting.

Starvation ensues when the fat reserves are completely exhausted and protein is the only fuel source available to the body. 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.[citation needed] (In a leaner person, the fat reserves are depleted earlier, the protein depletion occurs sooner, and therefore death occurs sooner.)

The ultimate cause of death is, in general,

cardiac arrhythmia or cardiac arrest brought on by tissue degradation and electrolyte
imbalances.

In the very obese, it has been shown that proteins can be depleted first. Accordingly, death from starvation is predicted to occur before fat reserves are used up.[7]

Biochemistry

During starvation, less than half of the energy used by the brain comes from metabolized glucose. Because the human brain can use

cognitive function and mobility for up to several weeks. This response is extremely important in human evolution and allowed for humans to continue to find food effectively even in the face of prolonged starvation.[8]

Initially, the level of

striated muscles). The body also engages in gluconeogenesis to convert glycerol and glucogenic amino acids into glucose for metabolism. Another adaptation is the Cori cycle, which involves shuttling lipid-derived energy in glucose to peripheral glycolytic tissues, which in turn send the lactate back to the liver
for resynthesis to glucose. Because of these processes, blood glucose levels remain relatively stable during prolonged starvation.

However, the main source of energy during prolonged starvation is derived from

perilipin. These enzymes, along with CGI-58 and adipose triglyceride lipase (ATGL), complex at the surface of lipid droplets. The concerted action of ATGL and HSL liberates the first two fatty acids. Cellular monoacylglycerol lipase (MGL), liberates the final fatty acid. The remaining glycerol enters gluconeogenesis.[11]

Fatty acids cannot be used as a direct fuel source. They must first undergo

TCA cycle and undergoes oxidative phosphorylation to produce ATP. The body invests some of this ATP in gluconeogenesis to produce more glucose.[12]

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. Acetoacetate breaks down spontaneously into acetone, and the acetone is released through the urine and lungs to produce the “acetone breath” that accompanies prolonged fasting. The brain also uses glucose during starvation, but most of the body's glucose is allocated to the skeletal muscles and red blood cells. The cost of the brain using too much glucose is muscle loss. If the brain and muscles relied entirely on glucose, the body would lose 50% of its nitrogen content in 8–10 days.[13]

After prolonged fasting,[clarification needed] the body begins to degrade its own skeletal muscle. To keep the brain functioning, gluconeogenesis continues to generate glucose, but glucogenic amino acids—primarily alanine—are required. These come from the skeletal muscle. Late in starvation, when blood ketone levels reach 5-7 mM, ketone use in the brain rises, while ketone use in muscles drops.[14]

Autophagy then occurs at an accelerated rate. In autophagy, cells cannibalize critical molecules to produce amino acids for gluconeogenesis. 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.[citation needed]

In bacteria

Bacteria become highly tolerant to antibiotics when nutrients are limited. 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.[18][19][20] Starvation in biofilms is due to nutrient consumption by cells located on the periphery of biofilm clusters and by reduced diffusion of substrates through the biofilm.[21] Biofilm bacteria shows extreme tolerance to almost all antibiotic classes, and supplying limiting substrates can restore sensitivity.[22]

See also

References

  1. ^ Adapted from Wang et al. 2006, p 223.
  2. ^ Therapeutic Fasting
  3. ^ Couch, Sarah C. (7 April 2006). "Ask an Expert: Fasting and starvation mode". University of Cincinnati (NetWellness). Archived from the original on 19 July 2011.
  4. PMID 11010936
    .
  5. PMID 22232606
    .
  6. ^ C. J. Coffee, Quick Look: Metabolism, Hayes Barton Press, Dec 1, 2004, p.169
  7. PMID 9665093
    .
  8. PMID 12813917
    .
  9. ^ Zauner, C., Schneeweiss, B., Kranz, A., Madl, C., Ratheiser, K., Kramer, L., ... & Lenz, K. (2000). Resting energy expenditure in short-term starvation is increased as a result of an increase in serum norepinephrine. The American Journal of Clinical Nutrition, 71(6), 1511-1515.
  10. ^ Clark, Nancy. Nancy Clark's Sports Nutrition Guidebook. Champaign, IL: Human Kinetics, 2008. pg. 111
  11. PMID 15136565
    .
  12. ^ Zechner, R, Kienesberger, PC, Haemmerle, G, Zimmermann, R and Lass, A (2009) Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores, J Lipid Res, 50, 3-21
  13. ^ McCue, MD (2010) Starvation physiology: reviewing the different strategies animals use to survive a common challenge, Comp Biochem Physiol, 156, 1-18
  14. PMID 4915800
    .
  15. PMID 16247502
    .
  16. PMID 13531168
    .
  17. S2CID 40134313
    .
  18. S2CID 10216159
    .
  19. S2CID 6670040
    .
  20. PMID 14527295
    .
  21. S2CID 5477887
    .
  22. PMID 16377718
    .

Resources

Retrieved from "https://en.wikipedia.org/w/index.php?title=Starvation_response&oldid=1211047830"