From the Guidelines
During starvation, epinephrine and norepinephrine trigger lipolysis in adipose tissue through a specific signaling cascade, which is crucial for survival by providing essential energy substrates when glucose is limited. The process begins with the binding of these catecholamines to β-adrenergic receptors on adipocyte cell membranes, activating adenylyl cyclase via stimulatory G proteins, as described in general metabolic pathways 1. This increases intracellular cAMP levels, which activates protein kinase A (PKA). PKA then phosphorylates hormone-sensitive lipase (HSL) and perilipin, a protein coating lipid droplets. Phosphorylated perilipin changes conformation, allowing HSL access to stored triglycerides. HSL hydrolyzes triglycerides into glycerol and free fatty acids.
After five days of starvation, this process is enhanced as insulin levels are low, removing the inhibitory effect on lipolysis. Additionally, prolonged fasting increases adipose tissue sensitivity to catecholamines, as seen in various metabolic adaptations during starvation 1. The released free fatty acids enter the bloodstream bound to albumin and are transported to the liver and muscle, where they undergo beta-oxidation to produce acetyl-CoA for energy via the TCA cycle or ketone body production.
Key steps in this process include:
- Binding of epinephrine and norepinephrine to β-adrenergic receptors
- Activation of adenylyl cyclase and increase in intracellular cAMP
- Activation of PKA and phosphorylation of HSL and perilipin
- Hydrolysis of triglycerides into glycerol and free fatty acids by HSL
- Transport of free fatty acids to the liver and muscle for energy production, which is vital for survival during prolonged fasting, as highlighted by the importance of metabolic adaptation in starvation and infection 1.
This mobilization of fat stores is essential for providing energy during starvation when glucose levels are low, and understanding these metabolic pathways can inform clinical practice, particularly in managing patients with malnutrition or those undergoing prolonged fasting 1.
From the Research
Breakdown of Stored Fuel in Adipose Tissues
The breakdown of stored fuel in adipose tissues of a person who has starved for five days involves a complex sequence of signaling and biochemical events. The key players in this process are epinephrine and norepinephrine, which are catecholamines that activate the membrane transport of long chain fatty acids in adipocytes 2.
Signaling Events
The signaling events involved in the breakdown of stored fuel in adipose tissues are as follows:
- Epinephrine and norepinephrine bind to beta-adrenergic receptors on the surface of adipocytes, activating adenylate cyclase and increasing intracellular levels of cAMP 3.
- The increase in cAMP activates protein kinase A (PKA), which phosphorylates and activates hormone-sensitive lipase (HSL) 4.
- Phosphorylated HSL translocates to the lipid droplet and breaks down triglycerides into fatty acids and glycerol.
Biochemical Events
The biochemical events involved in the breakdown of stored fuel in adipose tissues are as follows:
- The breakdown of triglycerides by HSL releases fatty acids into the cytosol, which are then transported out of the adipocyte and into the bloodstream 2.
- The fatty acids are then transported to other tissues, such as the liver, where they can be oxidized for energy or used for other purposes.
- The increase in fatty acid release from adipose tissue is accompanied by an increase in glucose production in the liver, as the body adapts to using alternative sources of energy during starvation 5.
Key Regulators
The key regulators of the breakdown of stored fuel in adipose tissues are:
- Epinephrine and norepinephrine, which activate the signaling cascade leading to HSL activation 2, 3.
- PKA, which phosphorylates and activates HSL 4.
- HSL, which breaks down triglycerides into fatty acids and glycerol 4.
- Beta-adrenergic receptors, which mediate the effects of epinephrine and norepinephrine on adipocytes 6.