Hormonal Regulation of Adipose Tissue During Starvation
The onset of starvation triggers a finely tuned endocrine response that reverses the fed state's metabolic priorities. When glucose levels decline, insulin secretion from the pancreas decreases significantly, effectively removing the primary brake on fat breakdown. Simultaneously, the release of counter-regulatory hormones, such as glucagon, catecholamines (epinephrine and norepinephrine), cortisol, and growth hormone, increases dramatically.
- Decreased Insulin: Insulin's decline during starvation signals adipose tissue to release stored fat.
- Increased Catecholamines and Cortisol: These hormones directly activate lipolysis in fat cells.
- Glucagon's Indirect Role: Glucagon's effect on the liver supports the overall catabolic state that prompts fat mobilization.
The Activation of Lipolysis: Mobilizing Fat Stores
The central metabolic change in adipose tissue during starvation is the activation of lipolysis, breaking down stored triglycerides (TAGs) into glycerol and non-esterified fatty acids (NEFAs). This is catalyzed by several enzymes:
- Adipose Triglyceride Lipase (ATGL): Initiates lipolysis by cleaving the first fatty acid. Its activity increases during starvation.
- Hormone-Sensitive Lipase (HSL): Hydrolyzes the second and third fatty acids, activated by the same hormonal cascade as ATGL.
- Monoglyceride Lipase (MGL): Completes the process, yielding the final free fatty acid and glycerol.
Released NEFAs bind to albumin and are transported to other tissues for fuel.
A Comparison of Adipose Tissue Functions: Fed vs. Starved State
| Feature | Fed State | Starved State |
|---|---|---|
| Hormonal Milieu | High Insulin, Low Catecholamines | Low Insulin, High Catecholamines/Cortisol |
| Lipolysis (Fat Breakdown) | Suppressed | Maximally Activated |
| Lipogenesis (Fat Synthesis) | Active; promoted by insulin | Inactive; suppressed by low insulin |
| Glucose Uptake | High (insulin-stimulated GLUT4 translocation) | Low (reduced GLUT4 expression and translocation) |
| Fuel Output | None | Fatty Acids and Glycerol |
| Adipokine Production | Elevated Leptin | Decreased Leptin |
| LPL Activity | High (promotes fat storage) | Low (inhibited by ANGPTL4) |
The Fate of Adipose-Derived Fuels
Fatty acids and glycerol, products of lipolysis, support the body during starvation:
- Fatty Acids: Tissues switch from glucose to fatty acid oxidation. The liver uses fatty acids for ketogenesis, producing ketone bodies as an alternative brain fuel during prolonged fasting.
- Glycerol: Taken up by the liver and converted to glucose via gluconeogenesis, helping maintain blood glucose for dependent tissues.
Dynamic and Depot-Specific Changes
Metabolic changes are not uniform across all fat depots. Visceral fat is often mobilized more rapidly than subcutaneous fat. The differing responses suggest complex, depot-specific regulatory mechanisms. White adipose tissue may also acquire 'beige' characteristics during fasting, potentially altering energy expenditure.
Conclusion
Adipose tissue undergoes essential metabolic reprogramming during starvation. Driven by a shift away from insulin and towards catecholamines, it transitions from storing to mobilizing fat. The release of fatty acids and glycerol ensures a consistent fuel supply, with ketone bodies becoming a critical brain energy source. This metabolic flexibility is key to survival during food deprivation.
The Impact of Fasting on Adipose Tissue Metabolism
For a deeper dive into the specific enzymes and hormonal pathways involved, see the review article, "The impact of fasting on adipose tissue metabolism" from ScienceDirect.
