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Combating Fat

Roger Cone

Fat: Fighting the Obesity Epidemic. Robert Pool. x + 292 pp. Oxford University Press, 2001. $27.50.

In Fat: Fighting the Obesity Epidemic, Robert Pool sets out to do for modern obesity research what Natalie Angier did almost two decades ago in Natural Obsessions for the molecular genetics of cancer and the discovery of oncogenes: He puts a very human face on scientific discovery and offers nonspecialists, and even nonscientists, an opportunity to learn about the entire history and current status of the field while vicariously enjoying the thrill of discovery. The book thus belongs to a genre represented at its pinnacle by James Watson's The Double Helix.

There are many fascinating stories in the history of obesity research, and Pool tells several of them quite well. He describes much of the medical and psychological thinking about obesity over the past century, such as the rise and fall of the externality hypothesis—the notion that the obese overeat because they are inherently more sensitive to certain external cues than to internal physiological ones. He also discusses the fabulous physiological experiments by A. W. Hetherington and Stephen Ranson, Jules Hirsch, and Rudy Leibel, which demonstrate that energy stored in the form of fat tissue is homeostatically controlled by the hypothalamus. This work shows that the brain actively attempts to reestablish homeostasis by adjusting metabolism and hunger, driving an individual who has lost weight back to his or her prediet weight. Thus it explains why so few people who lose weight are able to keep it off over the long term.

Pool then discusses the history of research on the genetics of obesity in the mouse. Through a series of interviews with Douglas Coleman, he provides some insight into the tremendously important role of mouse genetics—and the Jackson Laboratory in Bar Harbor, Maine—in obesity research. The current obesity epidemic does not result solely from either the accumulation of "thrifty genes" or our "supersize" portions and high-fat diets, but rather from the interaction of such genetic and environmental factors. Pool drives home this point and puts the broad issue of genetics in proper context in his chapter on the plight of the Pima Indians: Since adopting a Western lifestyle incompatible with their unusually thrifty genes, the Pimas have become the second-fattest group of people in the world.

Unfortunately, Fat appears to be based on a rather limited set of interviews. Consequently, the book falls short with regard to the genetics of obesity and how genetic research has advanced our understanding of energy homeostasis. The Jackson Laboratory originally maintained strains of mice with five different mutant genes for obesity: obese, diabetes, fatty, tubby and agouti. But Pool focuses on only two of these, the obese and diabetes genes, research on which led to revelations about the fat hormone leptin and its receptor. He misses the story of the other obesity genes, agouti in particular, whose cloning and characterization have elucidated the neural pathways (such as the central melanocortin neurons) on which leptin acts. This is a shame: Leptin mutations as a cause of obesity are extremely rare, but, as Philippe Froguel and Steven O'Rahilly have demonstrated, mutations in the central melanocortin-4 receptor are a common cause of severe human obesity, accounting for up to 5 percent of cases.

Furthermore, Pool fails to discuss the most important intellectual development in the leptin field following the cloning of the hormone gene by Jeffrey Friedman. Friedman derived the term leptin from the Greek leptos, for thin. However, a 1996 article in Nature by Jeffrey Flier and colleagues of his at Harvard argued—and this is now widely accepted—that the primary physiological role for leptin is not to keep us from getting fat, but rather to prevent us from becoming too thin, by orchestrating the well-characterized starvation response. Flier argued that the elevated leptin levels in the obese mean that a rise in leptin was not meant, evolutionarily, to have an important role in constraining fat accumulation. He then showed that replacing the falling leptin levels that occur during starvation with exogenous hormone completely blocks the starvation response—that is, the endocrine and metabolic changes that occur during starvation to conserve energy stores.

Despite some technical errors and some gaps in coverage of important areas, this is a book that I would highly recommend, both for the historical coverage of the field and the tremendous insight of the final chapter. Here, Pool finally addresses how we will fight the obesity epidemic. Although the severely obese clearly are in need of pharmaceutical and perhaps even surgical treatments, I could not agree more with the author when he argues that we must not imagine a future in which large numbers of people (30 to 40 percent of the population) are allowed to become obese and are then treated pharmaceutically. The obesity epidemic is a result of the interaction of genes with environment, and quite simply, we need to change our environment.

Pool argues that we don't yet know enough about what causes obesity and that "until we know specifically what needs to be changed, we can't rework our environment to be more human-friendly." However, we have used social policy to clean up our environment without understanding all the complexities of ecosystems, and, to use a medical example, drug treatment programs and Alcoholics Anonymous experience some degree of success even though we don't yet fully understand what causes drug or alcohol addiction. In the public schools in Oregon that my children attend, nachos (40 percent of calories from fat) are on the lunch menu, the vending machines dispense soda in 24-ounce containers and the voters have rolled back school funding to the point that physical education classes have been eliminated in about half the schools. Surely some useful measures for slowing the obesity epidemic are so obvious that we need not await the results of further research before implementing them.—Roger D. Cone, Vollum Institute and the Department of Cell and Developmental Biology, School of Medicine, Oregon Health & Science University, Portland

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