In this Metabolic Classroom lecture, Dr. Ben Bikman explores the critical yet often overlooked role of fat tissue as an endocrine organ, not just a passive energy storage site.

Fat secretes dozens of bioactive hormones, collectively called adipokines, that influence everything from appetite and insulin sensitivity to inflammation and cardiovascular risk. He focuses primarily on leptin, adiponectin, and PAI-1 (plasminogen activator inhibitor-1), detailing how each one affects whole-body metabolism and health.

Leptin, produced by fat cells, signals the brain about the body’s energy stores, affecting long-term appetite and fertility more than immediate satiety. Paradoxically, individuals with obesity often have high leptin levels but suffer from leptin resistance, leading to persistent hunger and metabolic dysfunction. In contrast, adiponectin levels decrease as fat mass increases. Adiponectin plays a powerful protective role by enhancing insulin sensitivity, reducing inflammation, and promoting fat metabolism, making it a key marker of good metabolic health.

Ben also highlights PAI-1, a lesser-known adipokine secreted mainly by visceral fat, which inhibits the breakdown of blood clots, thereby raising cardiovascular disease risk. He further discusses other adipokines such as resistin, TNF-alpha, and angiotensinogen, which link excess fat mass to insulin resistance, inflammation, and hypertension.

Finally, he contrasts subcutaneous fat (more benign) with visceral fat (more harmful) and explains how brown fat offers unique metabolic benefits by promoting thermogenesis and thyroid hormone activation. The location and health of fat tissue matter just as much as its quantity.

Show Notes/References:

For complete show notes and references, we invite you to become a Ben Bikman Insider subscriber. As a subscriber, you’ll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A after the lecture with Ben, ad-free podcast episodes, show notes and references, Ben’s Research Reviews Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more: https://www.benbikman.com

#FatHormones #Leptin #Adiponectin #PAI1 #MetabolicHealth #FatLoss #InsulinResistance #Endocrinology #ObesityScience #SubcutaneousFat #VisceralFat #BrownFat #CardiovascularHealth #Inflammation #GlucoseControl #Ceramides #HormoneHealth #FatStorage #DrBenBikman #KetoScience

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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:

For complete show notes and references, we invite you to become a Ben Bikman Insider subscriber. As a subscriber, you’ll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A after the lecture with Ben, ad-free podcast episodes, show notes and references, Ben’s Research Reviews Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more: https://www.benbikman.com

#Cortisol #InsulinResistance #ChronicStress #GlucoseControl #MetabolicHealth #CushingsDisease #HormonalBalance #FatStorage #Ceramides #DrBenBikman #VisceralFat #FatLoss #SubcutaneousFat #BloodSugar #AppetiteRegulation #Type2Diabetes #Mitochondria #HPAaxis #CortisolAndCravings #FatDistribution

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In this lecture, Dr. Bikman presents a framework for understanding the two primary patterns of insulin resistance onset—what he terms “fast” and “slow” insulin resistance.

“Fast” insulin resistance happens quickly and can often be reversed just as rapidly. It’s typically triggered by three major factors: elevated insulin (from frequent carb consumption), stress hormones like cortisol and epinephrine, and inflammation (from infection, injury, or autoimmune activity). These triggers lead to the cellular accumulation of ceramides, which interfere with insulin signaling at the molecular level. The good news, he emphasizes, is that when these triggers are removed, the insulin resistance can often resolve quickly.

“Slow” insulin resistance, on the other hand, develops gradually and is more difficult to reverse. It begins in the fat cell, where prolonged exposure to insulin and excess calories causes hypertrophy—the fat cells get larger. As they grow, they become insulin resistant as a form of self-preservation, but this leads to a damaging cascade: elevated free fatty acids, chronic low-grade inflammation, and disruption of glucose control. Dr. Bikman describes how hypertrophic fat cells become hypoxic, triggering inflammation and impairing surrounding tissues.

Unlike the fast form, slow insulin resistance is rooted in long-term lifestyle habits and takes time to correct. The standard advice to “just cut calories” fails to address the core issue—chronically high insulin. Instead, Ben recommends that people first focus on lowering insulin through carbohydrate restriction, which naturally curbs hunger, boosts energy expenditure, and allows fat cells to shrink in a sustainable way.

He concludes that understanding whether your insulin resistance is fast or slow in origin can help shape more effective interventions. With better insight into the mechanisms—from ceramides to fat cell hypertrophy—comes better, more targeted strategies to improve metabolic health.

Show Notes/References:

For complete show notes and references, we invite you to become a Ben Bikman Insider subscriber. As a subscriber, you’ll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A after the lecture with Ben, ad-free podcast episodes, show notes and references, Ben’s Research Reviews Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more: https://www.benbikman.com

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