Scientific discussion of hypothalamic control of weight and mouse obesity genetics

24 maintain an individual's weight within a fairly narrow range. The signals are received in a structure at the base of the brain called the hypothalamus. The hypothalamus is involved in the control of many basic, subconscious drives and reflexes including sex, feeding, ageression, drinking, and regulation of body temperature. When rats received lesions in a particular subregion of the hypothalamus called the ventromedial area, they became obese. They behaved as if they were starving and compensated with an increase in food intake and a decrease in energy expenditure. Conversely, when a different part of the hypothalamus, called the lateral area, was destroyed, the rats behaved as if they had been overfed. They reduced food intake and increased energy use and thereby became dangerously lean. This is not just a rat trick: These experiments have been replicated in a wide variety of mammals, and humans who sustain damage to the ventromedial hypothalamus (usually from a tumor of the adjacent pituitary gland) will also increase their food intake and become obese. This model raises one obvious question: How does your hypothalamus know how much you weigh? Let's step back and play God for a moment. If you wanted to build this system, how would you do it? By measuring blood glucose? Fat deposits? Core body temperature? Pressure on the soles of the feet? This all remained a mystery until 1994, when Jeffrey Friedman and his colleagues at Rockefeller University reported their observations of two strains of mutant mouse, one called obese and the other called db. (These mutations were not created by scientists using genetic tricks but arose spontaneously in a breeding colony.) Both strains of mice were extremely fat, a trait that was passed on to their offspring in a simple, dominant pattern of inheritance, like eye color. This suggested that obesity in both obese and db mouse strains resulted from a mutation in a single gene in each case. Friedman's group was HOUSE_OVERSIGHT_029955