Control of Food Intake and Body Weight

The body is in a continual state of hunger, which is intermittently relieved by eating. This perpetual drive to eat is periodically suppressed by inhibitory impulses generated by such things as the presence of food in the gastrointestinal tract, the flow of nutrients into blood and other factors. After these "satiety factors" have dissipated, the desire to eat returns.

Why is it important to understand the factors that control food intake? At least two major areas of import come to mind:

• Obesity is the most prevalent nutritional disease of humans, dogs and cats in affluent societies such as ours, exceeding by far the number of nutritional deficiency diseases.
• Metabolic demands of people and animals increase with sickness or trauma, often in conjunction with anorexia. Sickness combined with anorexia leads to accelerated starvation.

Before going on, take a minute to reflect on observations you have already made about food intake, body weight and similar topics. You may have noticed, for instance, that:

• Most animals as adults maintain a remarkably constant body weight.
• When it's cold, animals and people eat more than when it's hot.
• Children maintain energy balance with wildly varying intakes of food per meal.

These kinds of observations suggest a very complex system in charge of regulating energy balance and body weight. What is known about control of food intake is often discussed in terms of short-term and long-term controls. This discussion will focus on the following areas:

• Role of the central nervous system
• Pregastric factors
• Gastrointestinal and postabsorptive factors
• Long-term controls

Role of the Central Nervous System

For many years, the hypothalamus was thought to be the key to control of food intake. This view derived from classic experiments in which food intake was studied in rats with lesions in various areas of the brain. Such studies clearly identified two regions in the hypothalamus that dramatically influence feeding behavior:

• Lateral hypothalamus (hunger center): animals with lesions in this area become anorectic and lose weight.
• Ventromedial hypothalamus (satiety center): animals with lesions in this area overeat and become obese.

Subsequent studies showed that, although these hypothalamic centers are clearly very important in controlling hunger and satiety, they don't explain the whole story.

Pregastric Factors

We all know of "environmental" conditions that can dramatically affect food intake. Consider which of the following items are likely important to animals, humans or both:

• Appearance of food: humans like or dislike certain meals based on visual appearance, but does your cat appreciate your buying fish-shaped food?
• Taste and/or odor of food: this is extremely important in all species.
• Learned preferences and aversions: Almost everyone has an aversion to one or more types of foods, and they also affect companion animals.
• Psychologic factors: mental states such as fear, depression and social interactions often affect food intake.

Never eat a live mole! This seagull did, the mole tried to tunnel out and they both died.

Understanding these factors is of particular importance to clinicians because they can be manipulated to manage anorectic patients.

Gastrointestinal and Postabsorptive Factors

The degree of gastrointestinal fill is the most important signal from the digestive tract per se - a full stomach and intestine induce satiety, probably via the vagus nerve relaying that fact back to the hypothalamus. Additionally, the enteric hormone cholecystokinin is well documented to induce satiety in experimental settings, while the hormone ghrelin seems to be a potent stimulator of appetite.

As nutrients such as glucose and amino acids are absorbed, their concentrations in blood rise, as do the concentration of several hormones (cholecystokinin as mentioned above, but also insulin and glucagon). These changes also have been linked to the sensation of hunger or satiety.

Long-term Control of Food Intake

Adult animals tend to maintain a relatively constant weight known as their "set weight". Much of this appears to be regulated on a time scale of weeks or longer.

If an animal is starved for a long period of time, then allowed access to food, it eats a far greater amount of food than a normal animal. Conversely, if an animal is force fed for several weeks, then allowed access to free choice food, it will not eat very much. In both cases, when weight returns to "set weight," feeding behavior normalizes.

An additional interesting observation is that when food is restricted, basal metabolic rate decreases, which is one reason that it is so difficult to lose weight by dieting.

It is clear that long term regulation of body weight results from a complex integration of a battery of hormonal, metabolic and neural signals. In view of how tightly body weight is regulated in the face of widely varying levels of food intake and energy expenditure, it is clear that robust feedback systems are in place.

Searching for the feedback signals - "satiety factors" - has been a holy quest in this field for many years and has recently borne fruit, thanks to studies conducted years ago on mice with genetic mutations that cause obesity.

The satiety factor studied most extensively to date is the hormone leptin, which has the following basic characteristics:

• Leptin is synthesized and secreted predominantly by fat cells (adipocytes).
• A major site of leptin receptors is in the hypothalamus, which is known to play an important role in control of food intake and metabolic rate.
• Plasma levels of leptin rise and fall in parallel with body fat content - as body fat mass increases, so does the concentration of leptin in blood.
• Injection of leptin into leptin-deficient animals leads to reduction in body weight by suppressing food intake and increasing metabolic rate and energy expenditure.

Several other genes have been isolated that encode proteins that affect food intake, energy metabolism and body weight. Right now it is difficult to predict their future role in the pharmaceutical control of obesity, but needless to say, a number of companies are betting multimillions that one of more of these proteins will become the miracle drug for treatment of obesity.

References and Reviews

• Hill JO, Peters JC: Environmental contributions to the obesity epidemic. Science 280:1371, 1998.
• Martin RJ, White BD, Hulsey MG: The regulation of body weight. Amer Scientist 79:528, 1991.
• Rosenbaum M, Leibel RL, Hirsch J: Obesity. New Eng J Med 337:396, 1997.

Advanced and Supplemental Topics

• Genetics of Food Intake, Body Weight and Obesity