December 17, 2018

Nutritional Biochemistry

#33 – Rudy Leibel, M.D.: Finding the obesity gene and discovering leptin

"I've always felt that it was really somehow an enormous opportunity and a gift to be able to pursue this down to the level that I've been able to do in the past 30 years." —Rudy Leibel

Read Time 82 minutes

In this episode, Dr. Rudy Leibel, an expert in Clinical Molecular Genetics and Genomics at Columbia University, discusses his role in the remarkable scientific story of discovering leptin. He also gets into the genetics of obesity, as well as a broader discussion of the causes and effects of obesity, energy expenditure, and metabolism.


We discuss:

  • Rudy’s background, interest in obesity, and trying to understand the role and impact of adipose tissue [4:15];
  • Finding the first evidence of leptin by studying obese mice [23:30];
  • Zucker rats, and the push/pull theories of obesity [34:45];
  • A breakthrough in obesity research, and closing in on leptin [45:45];
  • Understanding leptin in humans [1:03:30];
  • What Prader–Willi syndrome teaches us about body weight regulation [1:09:45];
  • Leptin and the broad condition of obesity, metabolic consequences of weight reduction, and Peter’s self-experiments [1:18:00];
  • How is appetite being regulated? [1:29:45];
  • Are there epigenetic consequences of being obese? [1:37:00];
  • What makes low-carb diets so effective at obesity reduction? [1:46:15];
  • What did Rudy believe 10 years ago that he no longer believes to be true? [1:55:15];
  • Rudy’s dream study of the FTO gene [1:57:15];
  • What the hell does insulin resistance actually mean? [2:08:30]; and
  • More.


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Rudolph Leibel, M.D.

Dr. Leibel’s research focuses on the genetics of obesity and noninsulin-dependent diabetes. His laboratory has mapped, cloned, and identified mutations in the obese and fatty genes in rats, mice, and, more recently, in humans. The obese gene encodes leptin, an adipose derived hormone responsible for regulating body weight, whereas the fatty gene encodes the leptin receptor. Currently, his research group is defining the physiological bases by which this and related signaling networks regulate body size and composition. For example, changes in leptin production following reduction in body fat might play a role in the metabolic changes that accompany weight loss in humans. Dr. Leibel’s laboratory is also working to isolate additional rodent genes that influence body weight and the susceptibility to noninsulin dependent diabetes mellitus in the context of obesity. Laboratory members have extended their genetic studies to search for similar obesity and diabetes related genes in human families. []

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  1. There’s no doubt some people are genetically predisposed to obesity more than others and evolutionarily it would have likely been beneficial, but I don’t feel that looking for the genetic drivers and treatment based on those findings is helpful for moving the needle back in the right direction. I’m a much bigger believer in Dr. Lustig’s approach to the problem. We’ve gotta change the environment and/or educate the masses, both of which are daunting tasks, given the amount of misinformation out there. I certainly appreciate all of the work that you and your team do making this information available. Your work is influential and meaningful in ways that aren’t measurable. It resonates with me particularly as someone with a clinical interest in reversing these population trends, reducing health care costs, and improving lives through a proactive and preventative approach. Metabolic syndrome and it’s downstream effects needs to be public enemy #1 as smoking was decades earlier. People’s lives are too important and we quite literally can’t afford to keep the status quo.

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