Secret Science Club Post Lecture Recap: Leptin and Lipids

Last night, I headed down to the beautiful Bell House in the Gowanus section of Brooklyn for the latest Secret Science Club lecture featuring Lasker Award winning biologist Dr (MD and PhD) Jeffrey Friedman of Rockefeller University. Dr Friedman's official title for the lecture was "Leptin and the Biologic Basis of Obesity".

Dr Friedman began his lecture by noting that the topic of obesity was more personal that, for instance, the Large Hadron Collider, and he asked the audience to suspend any preconceived notions about the subject. He then noted that, after the main topic, he would briefly discuss the hedonistic value of food.

He then moved on to the question, why are obese individuals obese? Why does a particular individual eat too much? Before answering the questions, he indicated that obesity must be deconstructed- how do we define and measure obesity, and what causes the problem? An individual is considered overweight when their body fat equals or exceeds 20%, and obese when body fat equals or exceeds 30%. An individual with over 25% body fat has an increased risk of health problems and an individual with body fat exceeding 30% is at risk of increased mortality. Overweight individuals are at an increased risk of coronary disease, hypertension, steatosis, and diabetes. Given the health problems and the social stigma attached to obesity, why don't people lose the weight? Dr Friedman asked for an audience response- is it a lack of willpower? Environment and lifestyle? Genes? The answer he provided is that it is all three.

70-95% of diets fail within two years. Weight problems involve the First Law of Thermodynamics- if energy input exceeds energy utilized, the excess energy is stored as fat. Generally, weight is fairly stable in people unless they are trying to change their weight, with a typical person gaining ten pounds per decade. The typical body has a biological system which "counts calories". In an experiment, rats which were force fed reduced their voluntary caloric intake for a few weeks after their forced feeding. Similarly, rats which received a reduced caloric intake for a few weeks consumed more calories for a few weeks after their deprivation. There was a biological "drive" which returned the animals to a normal weight range.

Dr Lasker went on a brief tangent regarding the history of obesity, noting that obesity is not a new phenomenon, illustrated by a slide of the Venus of Willendorf. He then displayed a 1727 quote by one Thomas Short: “I believe no Age did ever afford more Instances of Corpulency than our own.” Dr Laser then indicated that the obesity rate in the West has doubled since 1980. The typical characterization of the doubling of the rate is that genes haven't changed, but the environment has. In a short time, the average weight gain was only 7-10 lbs, but the problem with the statistics is that obesity is a fixed threshold, while weight is a continuous variable. Slight weight gains can push an individual into the "obese" category.

Unlimited access to calories is one major environmental factor in the increased incidence of obesity, but there is a heritability factor. A hormone called leptin helps to regulate appetite- leptin sends a signal to the hypothalamus indicating that an individual has reached satiation. Individuals who lack leptin in the blood tend to be obese because they are not sated. Leptin also helps to regulate activity- leptin lacking individuals tend to be lethargic. The appetite stimulating counterpart to leptin is ghrelin. While rare individuals lack leptin, obesity is usually not a leptin deficiency, obese individuals typically have high leptin levels but they have a hormone resistance syndrome (similarly, type 2 diabetes involves insulin resistance, not a lack of insulin). The signal sent by leptin to the hypothalamus is weaker. Giving extra leptin to obese individuals did result in weight loss, but the amount of leptin needed was unfeasible to administer in a commercial setting- individuals would have needed 2 milliliter injections twice a day. Smaller amounts of leptin had no observable effect. One possible clinical approach to leptin resistance would be finding leptin sensitizers.

Feeding is regulated by two systems, a short term one and a long term one- the long term system depends on leptin and regulates the amount of fat that is stored, the short term system maintains high nutrient levels throughout the day and regulates feeding during the day- it involves neural factors and peptide hormones such as insulin and amylin.

There is an evolutionary component to the typical weight range of an animal- if an animal is too lean, there is an increased risk of starvation, if it is too fat, there is an increased risk of predation. There is not much difference between the hypothalamus of a fish and that of a human, the mechanisms which stimulate and inhibit feeding do not differ much among the vertebrates. In a typical vertebrate, feeding is homeostatic- a stable condition is maintained in most cases.

Dr Friedman then went on to discuss an experiment regarding the hedonistic value of food. Feeding is a complex behavior, involving not only hormones, but also smell, emotion, volition, and vision. In one study, the "reward center" of the midbrain of a mouse was altered so that it could be stimulated with a laser, resulting in a release of dopamine. The laser could be activated by the animal licking a sensor, and the neurons would be activated. Activating the neurons activated a behavior- the light would provide a stimulus to eat more.

In his closing, Dr Friedman noted that Hippocrates advised overweight individuals to eat less and exercise more, but he noted that we could do better than to repeat 2000 year old advice. He exhorted us to concentrate more on our health than our weight, but advised anyone with weight-related health consequences to try to lose a modest amount of weight- even the loss of ten pounds can make a difference. He ended up by telling us that we shouldn't berate ourselves for not being able to lose weight, we're fighting against powerful biological forces, then he told us not to berate others about their weight. In the Q&A, some bastard was going to ask about the role of our microbiomes in weight regulation, but some d00d beat me to the punch. Dr Friedman didn't have much to say about our bacterial fellow travelers, indicating that food intake and activity levels were of paramount importance.

Poking around the t00bz, I found a video of Dr Friedman giving an almost identical lecture:





Grab yourself a beer and watch it for a slight taste of the "Secret Science" experience.