In a pithy introduction, Smith beautifully outlines how, when scientists approach behavioral analysis with a "top down" strategy, they can eventually understand much about the cellular and molecular basis of behavior. The Bourne Laboratory convincingly demonstrated the importance of pregastric, gastric, and postgastric signals acting in synergy to produce satiation. From the original studies of Gibbs and Smith in 1973 demonstrating that the gastrointestinal hormone cholecystokinin reduced food intake, the laboratory has been a pioneer in demonstrating how the interaction between gastrointestinal peptides and afferent vagal fibers provides feedback concerning the state of satiation of the gut to the central feeding system.
Two chapters superbly dissect the evidence that both cholecystokinin and bombesin-like peptides serve as signals of the state of fullness of the gut. Many of us will have little trouble remembering the bitter altercations at meetings during the 1970s and 1980s, when it was argued that these hormones were nothing more than aversive agents that had nothing to do with normal behavior. Now we readily accept that other gut hormones, such as glucagon (solidly reviewed in a chapter by Nori Geary) and amylin (strangely ignored except for a brief mention as the possible mediator of the satiation effects of glucagon), have a role in producing the satiating effect of a meal.
As a clinician, I find the chapter on insulin as a satiating agent disturbing, since it is clear that insulin tends to stimulate appetite in diabetic patients, and when glucose levels are clamped, insulin has no effect on appetite. Most of the experiments in animals have relied on pharmacologic doses of insulin, but there is little evidence of a physiologically important role of insulin in the regulation of food intake. Despite this, the role of insulin as a satiating agent has achieved mythological importance.
The concluding chapters provide a discussion of the role of serotonin as a central and peripheral satiating agent and an interesting review of the role of satiation in limiting alcohol intake. This latter chapter concludes, as Richter did more than 70 years before, that alcohol satiation is related more to metabolism and clearance than to gastrointestinal processes.
I greatly enjoyed this historical romp through the field of gastrointestinal satiation. But for many readers of the Journal, the failure to provide an in-depth review of human studies could be the book's Achilles' heel. I would have liked more information on the satiating effects of various foods and on the relation between gastric emptying and satiation. The lack of chapters on leptin and the central feeding stimulants, such as neuropeptide Y, dynorphin, and the newly discovered orexins, and the central feeding inhibitors, such as corticotropin-releasing peptide, may leave the neophyte believing that the gut's the thing, whereas the leading players in the unfolding drama of appetite regulation appear to be in the brain and adipose tissue. Gut peptides appear to have only a supporting role in the long-term regulation of food intake and body mass.
This book reminds us that Freud's psychoanalytic theory would have been far more likely to stand the test of time if he had realized that food, not sex, is the central component of all life. Satiation dissects the relatively simple behavior of satiation at a molecular level in rodents but leaves us pondering the enormity of exploring the molecular mechanisms underpinning human behavior. As the English philosopher Emerson Pugh once remarked, "If the human brain was so simple that we understood it, we would be so simple that we couldn't."
Reviewed by John E. Morley, M.B., B.Ch.
Copyright © 1998 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.
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