This week, Dr. Bikman dives deep into the metabolic role of cortisol, the body’s primary glucocorticoid. He explains that while cortisol is essential for survival—mobilizing energy during fasting or stress—chronically elevated levels can wreak metabolic havoc.
Cortisol is produced by the adrenal cortex under direction from the hypothalamic-pituitary-adrenal (HPA) axis. Its main role is to ensure energy availability, stimulating glycogen breakdown, muscle catabolism, and fat breakdown in specific depots. However, long-term cortisol elevation, such as in Cushing’s disease, leads to fat redistribution, muscle loss, insulin resistance, and increased risk of type 2 diabetes.
Cortisol’s metabolic effects are driven by its action on glucocorticoid receptors inside cells, activating genes like PEPCK and glucose-6-phosphatase that stimulate gluconeogenesis and increase blood sugar. It also indirectly causes insulin resistance by increasing ceramide accumulation, which interferes with insulin signaling in cells like muscle and fat. This, combined with glucose overproduction and muscle loss (the major glucose sink), creates a perfect metabolic storm: high blood sugar, high insulin, and reduced glucose uptake.
The hormone also affects fat storage patterns. Cortisol enhances fat accumulation in visceral (abdominal) fat while stimulating fat loss in subcutaneous regions like the limbs. It increases fat uptake by upregulating lipoprotein lipase and blocks fat breakdown by suppressing hormone-sensitive lipase, especially in the abdominal region. Yet cortisol alone isn’t enough to cause fat gain—insulin is still required. Ben illustrates this by showing how individuals with untreated type 1 diabetes have high cortisol and high appetite but still lose fat without insulin.
Lastly, cortisol influences the brain’s hunger and reward systems, increasing carbohydrate cravings through neuropeptide Y and dopamine signaling. Chronic stress or medical conditions that elevate cortisol can drive overeating and central obesity. In short, while cortisol is necessary, its chronic elevation leads to insulin resistance, fat redistribution, and loss of metabolic control.
Show Notes/References:
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The Metabolic Classroom with Dr. Ben Bikman