Randy Nesse recently reviewed a new book (“The Evolution of Obesity” by Power and Schulkin) on weight regulation [Nature, 2009)]. In the course of the review, Nesse took note of the authors’ evidence that leptin-associated function is highly context-dependent, where context includes tissue, age, general organismal condition, and the concentrations of other molecules that regulate metabolism. Consequently, Nesse concluded that, “Attributing one function to a hormone is attractive, but often wrong.”
Based on the preceding, it would be reasonable to expect that the gene encoding leptin would exhibit pleiotropy, the property by which mutations of a single gene can influence multiple traits or phenotypes. Evidence supporting this inference has been obtained in mice, where homozygosity for a nonsense mutation that shortens the leptin gene product and causes deficient signaling through the leptin receptor is associated with phenotypes including increased body weight, decreased fat-free body mass, decreased lung and mammary tumor incidence, increased blood concentrations of insulin and cortisol, and decreased fertility relative to control, leptin-replete mice (Wolff, GL. J Nutr. 1997).
An experience that brought to mind Nesse’s point about hormones frequently having multiple functions was my recent reading of Michael Sandel’s book, “The Case Against Perfection: Ethics in the Age of Genetic Engineering.” (more…)