What triggers insulin resistance in adipose tissue?

I’m joined by Dr Robert Eckel to unpack why obesity is far more complex than a BMI number and why insulin resistance plays such a central role in cardiometabolic disease.

We discuss preclinical versus clinical obesity, fat distribution, metabolic risk, and what actually improves health outcomes beyond weight loss alone.

What We Cover

• Why BMI is only a starting point
• Preclinical versus clinical obesity explained
• Why visceral fat matters more than total fat
• How insulin resistance develops with excess body fat
• Who may benefit most from weight loss interventions
• GLP-1 therapies, benefits and open questions

A practical, evidence-based conversation that reframes how we think about obesity, risk and long term health.

• Introduction (00:00)
• Clinical vs Preclinical Obesity: How Should Obesity Be Defined? (05:21)
• Why Is Obesity Difficult to Diagnose and Treat in Practice? (08:06)
• How Genetics and Environment Influence Body Fat Gain (20:27)
• What Is Insulin Resistance and Metabolic Syndrome? (32:23)
• How Insulin Sensitivity Relates to Clinical Obesity (55:26)
• Why Insulin Resistance Begins in Adipose Tissue (59:49)
• Physiological vs Pathological Insulin Resistance Explained (01:04:47)
• How Physical Activity Improves Insulin Sensitivity (01:10:46)
• Family History, Genetics, and Cardiometabolic Risk (01:12:30)
• Individualised Obesity Treatment Guidelines in Clinical Care (01:15:40)
• How GLP-1 Receptor Agonists Are Used in Obesity Management (01:16:12)
• What Is the Obesity Paradox in Cardiometabolic Disease? (01:22:01)
• Future Projections for Obesity and Cardiometabolic Health (01:30:07)
• Public Health Challenges in Preventing Excess Adiposity (01:40:23)
• Practical Clinical Takeaways and Final Thoughts (01:44:15)

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Simon Hill, MSc, BSc (Hons)

• Creator of theproof.com
• Host of The Proof with Simon Hill
• Author of The Proof is in the Plants

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