Does elevated cortisol increase the release of free fatty acids?

Does Elevated Cortisol Increase the Release of Free Fatty Acids?

Yes, elevated cortisol definitively increases the release of free fatty acids (FFAs) from adipose tissue through stimulation of lipolysis, which contributes to insulin resistance and metabolic complications. 1

Mechanism of Cortisol-Induced FFA Release

Cortisol affects lipid metabolism through several pathways:

1. Direct stimulation of lipolysis:

   • Cortisol activates hormone-sensitive lipase in adipose tissue, leading to breakdown of stored triglycerides 1
   • This results in increased release of FFAs into circulation from peripheral adipose stores 1

2. Insulin resistance promotion:

   • Cortisol induces peripheral insulin resistance 1
   • This insulin resistance further promotes lipolysis and FFA release 1
   • A vicious cycle develops as increased FFAs further aggravate insulin resistance 1

3. Metabolic pathway alterations:

   • Cortisol increases gluconeogenesis and hepatic glucose production 2
   • Elevated glucose and insulin levels augment de novo lipogenesis 3
   • Cortisol stimulates uptake of circulating FFAs by the liver 3

Clinical Implications

The cortisol-induced increase in FFAs has significant clinical consequences:

• Cardiovascular risk: FFAs released due to cortisol can be potentially harmful to the myocardium 1
• Metabolic syndrome development: Hypercortisolemia leads to visceral obesity and is linked to metabolic syndrome 1
• Insulin resistance: The American Heart Association notes that cortisol is important both in increasing visceral adiposity and promoting metabolic syndrome 1
• Perioperative complications: During surgical stress, cortisol-induced FFA release can worsen insulin resistance and contribute to stress hyperglycemia 1, 4

Pathological Consequences

In pathological conditions with elevated cortisol:

• Toxic accumulation: During severe systemic inflammation, plasma FFAs can increase up to four-fold 1
• Organ damage: Excessive FFAs can cause severe organ damage and interfere with mitochondrial function 1
• Protein catabolism: Cortisol-induced insulin resistance modifies protein metabolism, leading to increased protein breakdown and delayed healing 1
• Fatty liver development: Prolonged glucocorticoid exposure promotes hepatic lipid deposition through multiple mechanisms including increased FFA release from adipose tissue 3

Clinical Relevance in Specific Conditions

1. Perioperative setting:

   • Stress hormones (including cortisol) released during surgical stress lead to insulin resistance 1
   • This insulin resistance affects lipid metabolism with increased release of FFAs 1
   • Insulin therapy during surgery can mitigate the perioperative release of FFAs 1

2. Cushing's syndrome:

   • Hypercortisolemia leads to visceral obesity and cardiovascular complications 1
   • Even exogenous glucocorticoid administration is a risk factor for cardiovascular events 1

3. Diabetic ketoacidosis:

   • Elevated counterregulatory hormones (including cortisol) lead to increased release of FFAs 1
   • These FFAs undergo hepatic fatty acid oxidation to ketone bodies 1

Practical Considerations

When managing patients with conditions involving elevated cortisol:

• Monitor for metabolic derangements including hyperglycemia and dyslipidemia
• Consider the impact of exogenous glucocorticoid therapy on lipid metabolism
• Address insulin resistance to help mitigate FFA-related complications
• In perioperative settings, consider appropriate insulin therapy to reduce FFA release 4

The relationship between cortisol and FFA release represents an important pathophysiological mechanism that contributes to multiple metabolic disorders and their complications.