urge to eat, and satiety, or the inhibition of eating, are compensatory responses to these insulin-driven cycles of fat storage followed by fat mobilization. Insulin secretion is released in the morning upon waking and drives us to eat, Le Magnen concluded, and it ebbs after the last meal of the day to allow for prolonged sleep without hunger.
This hypothesis of eating behavior did away with set points and lipostats and relied instead on the physiological notion of hunger as a response to the availability of internal fuels and to the hormonal mechanisms of fuel partitioning. Hunger and satiety are manifestations of metabolic needs and physiological conditions at the cellular level, and so they’re driven by the body, no matter how much we like to think it’s our brains that are in control.
Several variations on this hypothesis were published from the mid-1970s onward by Le Magnen and others. The most comprehensive account was published in 1976 by Edward Stricker at the University of Pittsburgh, and Mark Friedman, then at the University of Massachusetts and now at the Monell Chemical Senses Center in Philadelphia. Their article, “The Physiological Psychology of Hunger: A Physiological Perspective,” should be required reading for anyone seriously interested in eating behavior and weight regulation.
The hypothesis is based on three fundamental propositions. The first, as Friedman and Stricker explained, is that the supply of fuel to all body tissues must always remain “adequate for them to function during all physiological conditions and even during prolonged food deprivation.” The second proposition is Hans Krebs’s revelation from the 1940s that each of the various metabolic fuels—protein, fats, and carbohydrates—is equally capable of supplying energy to meet the demands of the body. The third is that the body has no way of telling the difference between fuels from internal sources—the fat tissue, liver glycogen, muscle protein—and fuels that come from external sources—i.e., whatever we eat that day.
With these propositions in mind, the simplest possible explanation for feeding behavior is that we eat to maintain this flow of energy to cells—to maintain “caloric homeostasis”—rather than maintain body fat stores or some preferred weight. If the cells themselves are receiving sufficient fuel to function, the size of the fat reserves is a secondary concern. As Friedman and Stricker explained, “Hunger appears and disappears according to normally occurring fluctuations in the availability of utilizable metabolic fuels, regardless of which fuels they are and how full the storage reserves.” In 1993, the Princeton physiological psychologist Bartley Hoebel described the hypothesis in terms that echoed the origins of the theory in the work of Claude Bernard: “The primitive goal of feeding behavior,” Hoebel explained, “is to maintain constancy of the nutrient concentration of the milieu interieur.”
From this perspective, we’re not much more complicated than insects, which will seek out food and consume it until their guts are full. External taste receptors signal whether they’ve come upon something they can benefit from eating; gut receptors signal when sufficient food has been consumed to inhibit the hunger. The role of the brain is to integrate the sensory signals from the gut and the taste receptors and couple them to motor reflexes to initiate eating behavior or inhibit it. In both flies and mosquitoes, if the neural connection between gut and brain is severed, the insect loses its hunger inhibitor and continues to eat until its gut literally ruptures. As Edward Stricker explained in
The primary difference between humans and insects, by this logic, is that we have two primary fuel tanks (three if we include glycogen stored in the liver, and four if we include protein in the muscles), and they effectively have one. In our case, fuel is stored initially in the gut for the short term, and then in the fat tissue for the medium to longer term. The fat tissue extends the time we can go between meals by hours, days, or more. The fuel supply to the cells is maintained by the filling and emptying of both these energy reserves. “Energy metabolism,” Friedman and Stricker wrote, “is maintained by alternating tides of nutrients that sweep in from the intestines or adipose tissue at regular intervals depending on when food consumption occurs.” The fat tissue participates actively in metabolism by acting as an energy buffer: it provides storage for nutrients that arrive with the meal but are not immediately necessary for energy, and then it releases them back into the circulation as this absorptive phase is coming to an end. In effect, the fat tissue prevents dramatic shifts in the energy supply, which would otherwise be unavoidable considering the fact that, unlike cattle or sheep, we don’t graze continually but, rather, eat episodically in discrete meals.
We can think of eating and satiety as a cycle that begins with the meal and fills the gastrointestinal reserve— the gut. As nutrients are absorbed into the circulation, some are used for fuel immediately, and the rest restock the fat reserves, the glycogen reserves in the liver, and the protein in the muscles. As the gut empties, and this dietary fuel is either stored or oxidized, the fat reserves become the primary source of fuel. As the fat reserves begin to empty and the fuel flow shows signs of faltering, the inhibition of hunger is lifted, we are motivated again to fill the gut, and the cycle begins anew.
This “harmony of tissue metabolisms” is orchestrated by the hypothalamus, via the central nervous system and the endocrine system of hormones. These regulate the filling and emptying of the various storage depots in response to an environment that might require that we suddenly expend more or less energy, or store more or less fat, to accommodate seasonal variations. The hypothalamus does what the brains of insects do: it integrates sensory signals from the body and the rest of the brain, and couples them to motor reflexes that permit or restrain eating behavior. It also adjusts this filling and emptying of the fuel reserves to accommodate the immediate need for fuel and the anticipated need for fuel.
According to this hypothesis, weight stability is nothing more than an equilibrium between the fatty acids flowing into the energy buffer of the fat tissue and the fatty acids flowing out. What the body regulates, as Le Magnen suggested, is the fuel flow to the cells; the amount of body fat we accumulate is a secondary effect of the fuel partitioning that accomplishes this regulation.
The implication of this hypothesis is that both weight gain and hunger will be promoted by factors that work to deposit fatty acids in the fat tissue and inhibit their mobilization—i.e., anything that elevates insulin. Satiety and weight loss will be promoted by factors that increase the release of fatty acids from the fat tissue and direct them to the cells of the tissues and organs to be oxidized—anything that lowers insulin levels. Le Magnen himself demonstrated this in his animal experiments. When he infused insulin into rats, it lengthened the fat-storage phase of their day-night cycle, and it shortened the fat-mobilization-and-oxidation phase accordingly. Their diurnal cycle of energy balance was now out of balance: the rats accumulated more fat during their waking hours than they could mobilize and burn for fuel during their sleeping hours. They no longer balanced their overeating with an equivalent phase of undereating. Not only were their sleep-wake cycles disturbed, but the rats would be hungry during the daytime and continue to eat, when normally they would be living off the fat they had stored at night.*134 Indeed, when Le Magnen infused insulin into sleeping rats, they immediately woke and began eating, and they continued eating as long as the insulin infusion continued. When during their waking hours he infused adrenaline—a hormone that promotes the mobilization of fatty acids from the fat tissue—they stopped eating.
If this hypothesis holds for humans, it means we gain weight because our insulin remains elevated for longer than nature or evolution intended, and so we fail to balance the inevitable fat deposition with sufficient fat oxidation. Our periods of satiety are shortened, and we are driven to eat more often than we should. If we think of this system in terms of two fuel supplies, the immediate supply in the gut and the reserve in our fat deposits, both releasing fuel into the circulation for use by the tissues, then insulin renders the fat deposits temporarily invisible to the rest of the body by shutting down the flow of fatty acids out of the fat cells, while signaling the cells to continue burning glucose instead. As long as insulin levels remain elevated and the fat cells remain sensitive to the insulin, the use of fat for fuel is suppressed. We store more calories in this fat reserve than we should, and we hold on to these calories even when they’re required to supply energy to the cells. We can’t use this fat to forestall the return
