Lecture 10a   THE DUAL-CENTER SET-POINT MODEL OF EATINGCOURSE MATERIAL AND Pinel LECTURE NOTES

Outline:

     1.     The Early Studies
     2.     Glucostatic and Lipostatic Theories v. Positive-Incentive Theories
          a. Glucostatic and Lipostatic Theories
          b. Positive-Incentive Theories
     3.     Hypothalamic Hunger and Satiety Centers and The Dual-Center Set-Point Model
          a.     Ventromedial Hypothalamus
          b.     Lateral Hypothalamus
     4.     Positive-Incentive Models of Feeding
     5.     Current Research on the Biopsychology of Eating
          a.     Palatability and Positive Incentives
          b     Energy Expenditure and Body-Fat Homeostasis
          c.     Satiety Peptides
          d.     Reevaluation of the Role of the Ventral Hypothalamus
          e.     Role of Learning in Eating
     6.     A Settling-Point Model of Body-Weight Regulation

Lecture Notes

1.     The Early Studies (use Digital Image Archive Figure CH10F01.BMP)

Energy is available to the body in three forms:

     (1) lipids (fats),
     (2) proteins (broken into amino acids), and
     (3) glucose (simple sugar byproducts of carbohydrates)
Energy metabolism occurs in three phases (use Digital Image CH10F03.BMP);

     1) the cephalic phase (preparatory),
     2) absorptive phase (energy absorbed into the bloodstream), and
     3) the fasting phase (body utilizes food stores)

The first influential study of the physiological basis of hunger was conducted in 1912 by
Canon and Washburn;

Washburn swallowed a balloon on the end of a thin tube, the balloon was partially
inflated, and a pressure gauge was attached to the other end of the tube
each time that he had a large stomach contraction, Washburn reported a pang of
hunger; this led to the view that stomach contractions are a major factor in hunger.

But the finding that animals whose stomachs had been denervated or completely removed ate enough to maintain their body weights discredited this view;

in addition, people with no stomachs report feeling hungry and maintain their body weights; they eat less per meal, but they eat more meals

More recently, Koopman (use Digital Image Archive Figure CH10F12.BMP) has used a second-stomach preparation to implicate the gut in feeding behavior;

     Rats who have had a second stomach implanted into their peritoneum eat less when
the second stomach is loaded with food, even though the stomach is not innervated nor
are the nutrients able to be absorbed into the bloodstream.
2.     Glucostatic and Lipostatic Theories of Hunger

research on feeding has been heavily influenced by the idea of a feeding set-point,
based around the idea of a homeostatic, negative feedback system regulating feeding.

research on feeding has been strongly influenced by the idea that feeding is controlled by
deviations from two different set points:

     1. a set point for blood glucose (short-term regulation) and
     2. a set point for body fat (long-term regulation)

3.     Hypothalamic Hunger and Satiety Centers and The Dual-Center Set-Point Model

     In the 1950's, studies in which various areas of the rat hypothalamus were lesioned
or stimulated seemed to suggest that it contained the hypothesized hunger and satiety
centers

     a.     Ventromedial Hypothalamus (VMH) (use Digital Image CH10F08.BMP)

     Large bilateral lesions of the VMH produced hyperphagia and gross obesity; after
the lesion, the rats were extremely hyperphagic and gained weight rapidly (dynamic
phase);

     after several weeks hyperphagia was only slight and a new very high body weight was
defended (static phase)
     although several nuclei were damaged by the large VMH lesions, the syndrome was
typically attributed to ventromedial nucleus damage
two interpretations were proposed:

(1) that glucoreceptors and their associated satiety circuits had been destroyed, or

(2) that the body-fat set point had been increased

Electrical stimulation of the ventromedial nucleus caused hungry rats to stop eating;

     this finding is difficult to interpret due to the many reasons why electrical stimulation might have this effect (e.g., it might produce pain or nausea)

     b.     Lateral Hypothalamus (LH) (use Digital Image Figure CH10F08.BMP)

large bilateral lesions of the lateral hypothalamus rendered rats aphagic (refuse food) and adipsic (refuse water);

if force fed and then maintained on highly palatable wet diets, they eventually recovered to the point that they could maintain themselves on laboratory chow and water
lateral hypothalamic stimulation elicited feeding (and a variety of other motivated behaviors);

the fact that satiated rats ran a maze to obtain food if they were stimulated, suggested that lateral hypothalamic stimulation induced hunger rather than mere eating movements
these data led to the development of a dual-center, set-point model of feeding behavior; this model reigned supreme in the 1950s and 1960s.


the dual-center set-point model is based on two assumptions that have been rendered untenable by modern research:
     (1) that eating is normally a product of internal energy deficits;
     (2) that the homeostasis of the body's energy resources implies set-point regulation of eating

4.  Positive-Incentive Models of Feeding

-     there are many problems with the theory that deviations from a blood-glucose or fat set point are the primary signals for hunger and satiety, and that the VMH and the LH are the satiety and hunger centers in the brain, respectively
-     for example, the idea of set-point controls for feeding are not evolutionarily sound; major predictions of the theories have not been supported by research in the area (e.g., people with diabetes mellitus overeat despite very high blood glucose levels; data indicate that VMH lesions seem to disrupt metabolism rather than feeding, and may be due to damage to structures in the region of the VMH like the paraventricualr nucleus of the hypothalamus, rather than the VMH itself

-     in addition, , they do not recognize the major influences of taste, learning, and social factors on feeding.

-     recently, an alternative theory of feeding and hunger has emerged: the positive-incentive theory

-     this is based on the idea that we eat because eating is pleasurable, rather than to satisfy some setpoint for glucose or fat.  When good food is present we will eat…regardless of whether we actually need the food or not.  Hunger is determined by many factors including taste, previous experience with a food, time since your last meal, who you are eating with, etc.

5.     Current Research on Biopsychology of Eating

     Current research on the biopsychology of eating has seriously undermined the dual
          -center set-point theory and the assumptions on which it is based

     a.     Palatability and Positive Incentives

-     the idea that eating is rigidly controlled by deviations from internal set points is humbled by a piece of pecan pie and whipped cream served at the end of a large meal;
               in rats, a small amount of saccharin (Equal, Aspertame, etc.) added to their diet leads to an increase in consumption and marked weight gain

               Can you relate this finding to what is happening to Americans in term of getting fat???

-     These observations cannot be explained by the set-point theory;
     they have led to the idea that feeding is normally initiated by the positive-incentive
     properties of food (i.e., the anticipated pleasurable effects) rather than by internal deficits;
     the positive-incentive theory explains the effects of deprivation by assuming that deprivation increases a food's positive incentive properties--the anticipated pleasure from eating is assumed to be greater in individuals who have been deprived of food
     -     sensory-specific satiety also creastes problems;
               research suggests that eating a particular food reduces the incentive value of its taste more than that of other foods;

               So, if rats are offered a cafeteria diet, their consumption and weight increase dramatically; this is the kind of diet on which virtually all humans in industrialized societies currently exist; it is no wonder that obesity is a problem

     b.     Energy Expenditure and Body-Fat Homeostasis

     Another problem with the dual-center set-point model is that it assumes that all regulation of the body's energy resources occurs on the intake side of the system;
               there is now strong evidence that the body responds to energy shortages and excesses by increasing or decreasing the efficiency of energy utilization
     As individuals gain weight, more and more of the calories that are consumed are wasted by excess heat production (diet-induced thermogenesis)

     With decreased amounts of stored fat, the body naturally slows its metabolic rate; this saves energy resources but makes further weight loss more difficult.

     But,when more calories are consumed, the body no longer needs to conserve energy, thus metabolic rates increase and further weight gain becomes more difficult

     The interactions between energy resources of the body and the incentive properties of food have become important areas of research.

     c.     Satiety Peptides

     -     as noted earlier, several lines of recent research have suggested that food in the gastrointestinal tract causes the release of satiety signals

     -     for example, Koopman found that food injected into the stomach inhibits intake, even in vagotomized subjects and even when the food is not allowed to pass into the duodenum to be digested;

          perhaps this satiety signal is one of the many peptide hormones released from the gastrointestinal tract into the bloodstream

     -     cholecystokinin (CCK), bombesin, glucagon, and somatostatin injections have been shown to inhibit eating; recently, neuropeptide Y and galanin have been shown to increase feeding

d.     Reevaluation of the Role of the Ventral Hypothalamus

-     the hyperphagia and obesity produced by large bilateral VMH lesions was at first taken as evidence that the ventromedial nucleus is a satiety center;
          there are currently few adherents to this view
-     the current view is that the VMH controls energy metabolism not satiety; VMH lesions have been shown to increase lipogenesis (production and storage of body fat) and decrease lipolysis (breakdown and use of body fat)

-     paradoxically, it seems that rats with VMH lesions overeat because they are getting fat and not vice versa; in VMH-lesioned rats, glucose is continuously drawn from the blood and stored as fat, thus the rats must eat continually to supply themselves with a source of immediate energy

-     the following four observations support this view:

     (1) hyperinsulinemia is observed after VMH-lesions, even in rats not allowed to eat, and the degree of hyperinsulinemia in a particular animal predicts its subsequent weight gain;
     (2) rats with VMH lesions gain more weight than controls, even when they are not allowed to eat more than controls;
     (3) during the day, when they sleep, rats with VMH lesions get their energy from gluconeogenesis; and
     (4) cutting the branch of the vagus nerve that conducts signals from the hypothalamus to the pancreas eliminates the hyperinsulemia and the hyperphagia produced by VMH lesions

     Evidence indicates that many aspects of the VMH do not result from damage to the ventromedial nuclei per se;
          VMH lesions inevitably damage fibers coursing by the VMN on their way to the paraventricular nuclei (use Digital Image CH10F010.BMP);

     Hyperphagia, obesity, and hyperinsulemia are produced by discrete bilateral knife cuts to these passing fibers or to lesions of the paraventricular nuclei themselves

e.     Role of Learning in Eating

-     recent research has shown that learning can influence eating in a variety of ways
-     in general animals are born with a preference for sweet and salty tastes,
      and with an aversion to bitter tastes;

     but they learn to avoid any taste followed by illness (conditioned taste aversion) or to prefer tastes that improve their health (conditioned taste preference)

-     in the wild these forms of learning are robust and adaptive,

     however in modern industrialized societies people eat so many different tastes in a
               day that their bodies cannot learn the relations between taste and outcome;
     thus people who live in the midst of plenty often suffer from malnutrition because their bodies cannot learn the relation between various tastes and their health-promoting or health-disrupting effects
For example, when thiamin (Vitamin B1) deficient rats were offered three different
     diets, one of which had thiamin, within a few days all preferred the thiamin diet;
     however, when they were offered 10 new diets, few learned to consume the one with thiamin

Recent research by Weingarten and his colleagues suggests that nondeprived humans
     and animals learn to become hungry when they are used to eating, not when they
     have an energy deficit--nondeprived humans and animals do not normally have
     energy deficits when they begin meals

     Weingarten fed deprived rats 6 small meals per day of a highly palatable liquid diet
          at irregular intervals for 11 days;
       a buzzer-and-light conditional stimulus came on before each meal and stayed on during it
       next, Weingarten gave these same rats continuous access to the palatable liquid diet; despite the fact that they consumed large quantities of the liquid diet throughout the day, each time the buzzer and light were presented the rats consumed a meal

6.     A Settling-Point Model of Body-Weight Regulation (use Digital Image Archive Figure CH10F14.BMP)

The leaky-barrel model illustrates the ideas behind a settling-point theory of body weight regulation;
     in this model, the stability of body weight is the result of the stability of the various factors that influence energy intake and output;
     it accounts for the homeostasis of body weight without having to postulate a fixed set point, and it can also account for instances in which there are long-term changes in body weight, which a strict set-point model cannot
     in this model, a permanent change in factors that influence energy intake or output produces a change in the settling point that is partially offset by negative feedback from other factors

How does the settling point model account for the following common weight-change scenarios?  

(1) A dieter loses 20 pounds, stops dieting, and regains the weight.  

(2) A dieter consumes exactly 1,000 calories per day; at first weight is lost at a rapid rate, but after a few months no more weight is lost.  

(3) A woman marries a professional cook; at first, she gains weight rapidly but eventually her weight stabilizes, and she can't seem to lose it.


Suggested Websites for Lecture 10a:

The Hypothalamus: http://thalamus.wustl.edu/course/hypoANS.html
          From the Neuroscience Tutorial at Washington University's School of Medicine, a text-and-figure review of the anatomy, physiology, and function of the hypothalamus.


     The Dynamics of Digestion: http://www.sartek.com/HLWC/DOD.html
          From Luise Strehlow and the High Level Wellness page, an overview of ingestive behavior.  Nice links to figures that complement the text; easy reading.

     Recognizing and Treating Eating Disorders: http://www.aabainc.org/home.html
          The home page for the American Anorexia and Bulimia Association.  See also:          http://www.sciam.com/explorations/1998/030298eating/index.html
And
http://www.sciam.com/0896issue/0896gibbs.html

          From Scientific American, two articles examining the neural bases of feeding, satiety, and eating disorders.