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Nobel Conference: Jeffrey M. Friedman

“Leptin and the Biologic Basis of Obesity”

Jeffrey M. Friedman, M.D., Ph.D., Marilyn M. Simpson Professor and HHMI investigator, Laboratory of Molecular Genetics, and director, Starr Center for Human Genetics, The Rockefeller University, New York, N.Y.

Jeffrey Friedman provided the third lecture, which was essentially and introduction to why our cultural thinking on obesity is generally okay as far as it goes but doesn’t go nearly far enough. It also addressed the idea that our emotional reaction to fat, as a culture, is completely out of line with the facts behind fat. As before, below is my summary of the lecture in tweets. The full lecture, including the Q&A afterward with all the invited speakers, is available on YouTube.

Yes, obese people eat more and exercise less, but why?
Everyone has a set of convictions about obesity. Very little interest in hearing science-based answers.
Willpower as an explanation of differences in weight is most often favored by the lean.
Maintenance of weight under a variety of conditions suggests an inherent mechanism for balancing food intake and usage.
Mechanism will impose a basic drive in opposition to higher cognitive functions, no matter our desires.
Natural selection can act very powerfully over the short term. Recent increases in obesity not necessarily environmental.
BMI distributions don’t have to change much to see large *categorical* (overweight, obese) differences.
Obesity estimated to be as heritable as height.
Leptin a hormone that provides negative feedback between fat tissue and hypothalamus (my simplification).
Fat tissue is an endocrine organ. Lack of leptin causes a starvation response: extreme energy conservation.
Obesity appears to be a hormone-resistance syndrome, like Type II diabetes.
Adding much more leptin to the system can affect some patients, dosage required too high to be practical.
About 1/3 of obese sensitive to lower doses of added leptin.
May be use for leptin on conjunction with leptin sensitizers (short-term plus long-term agents). Still in trials. [Friedman noted potential conflict of interest in that he consults for the company developing the regimen.]
Studying signaling pathways in presence and absence of leptin to determine where weight is controlled.
10% of morbid obesity due to single-gene defects. More from multi-gene and gene-environment interactions.
We have a good grasp of the physiological cycle. Still working on neurological processing.
Metabolic, sensory, and cognitive factors affect likelihood of feeding behavior, but do not control directly.
Work on obesity has provided a framework for studying physiological/psychological systems.
Time to provide better advice to obese than “Eat less; exercise more,” which is millennia old.
Still things to do to protect health in the presence of obesity: exercise, eat well, stay at the leaner end of you weight range.
Vilification of the obese seems to be largely due to the human need to feel in control–or more than animals.
Good food choices? You don’t care what you eat when you think you’re starving.
Scientific debate ongoing over whether all calories are created equal with respect to long-term hunger signaling.

Comments

  1. says

    My only concern with this information is that overweight people (I am one) might think, well, I don't have a choice. I'm fat because I don't have/can't use leptin so I'll just keep eating. I've proven, so far, that eating less and exercising more works. Further thoughts?

  2. says

    a2z, how long have you maintained your lower weight? Has it not gone back up after a period at a lower weight?Nobody's saying this isn't a complicated picture with differences between individuals, and Dr. Friedman did end his lecture with things that have been shown to improve health for everyone. Those also happen to include behaviors that reduce weight in those who can. Besides, what alternative do you propose? The same old information that doesn't help people and leads to additional stress (something Friedman didn't address but which has been decidedly linked to weight problems)?

  3. says

    I've been 15 pounds lighter for nearly a year and have started that downward trend once again. I agree that it's not easy, but I have no excuse if I continue to eat more calories than I use. I can only speak for myself.