Transcript Document

Ingestive Behavior
Chapter 12
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COPYRIGHT © ALLYN & BACON 2012
Physiological Regulatory Mechanisms: Drinking
• Regulation of the fluid that bathes our cells is part of a process called homeostasis
(“similar standing”).
• Homeostasis (home ee oh stay sis)
• the process by which the body’s substances and characteristics (such as
temperature and glucose level) are maintained at their optimal level
• System Variable
• a variable that is controlled by a regulatory mechanism; for example, temperature in a
heating system
• Set Point
• the optimal value of the system variable in a regulatory mechanism
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Eating: Some Facts about Metabolism
• The short-term reservoir is located in the cells of the liver and the muscles, and it is filled
with a complex, insoluble carbohydrate called glycogen.
• For simplicity, I will consider only one of these locations: the liver.
• Glycogen (gly ko jen)
• a polysaccharide often referred to as animal starch; stored in liver and muscle;
constitutes the short-term store of nutrients
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Eating: Some Facts about Metabolism
• Cells in the liver convert glucose (a simple, soluble carbohydrate) into glycogen and store
the glycogen.
• They are stimulated to do so by the presence of insulin, a peptide hormone produced by
the pancreas.
• Insulin
• a pancreatic hormone that facilitates entry of glucose and amino acids into the cell,
conversion of glucose into glycogen, and transport of fats into adipose tissue
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Eating: Some Facts about Metabolism
• The fall in glucose is detected by cells in the pancreas and in the brain.
• The pancreas responds by stopping its secretion of insulin and starting to secrete a
different peptide hormone: glucagon.
• Glucagon (gloo ka gahn)
• a pancreatic hormone that promotes the conversion of liver glycogen into glucose
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Eating: Some Facts about Metabolism
• The effect of glucagon is opposite that of insulin: It stimulates the conversion of glycogen
into glucose. (Unfortunately, the terms glucose, glycogen, and glucagon are similar
enough that it is easy to confuse them. Even worse, you will soon encounter another one:
glycerol.) (See Figure 12.11.)
• Thus, the liver soaks up excess glucose and stores it as glycogen when plenty of glucose
is available, and it releases glucose from its reservoir when the digestive tract becomes
empty and the level of glucose in the blood begins to fall.
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Eating: Some Facts about Metabolism
• Our long-term reservoir consists of adipose tissue (fat tissue).
• Adipose tissue is found beneath the skin and in various locations in the abdominal cavity.
• This reservoir is filled with fats or, more precisely, with triglycerides.
• Triglyceride (try gliss er ide)
• the form of fat storage in adipose cells; consists of a molecule of glycerol joined with
three fatty acids
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Eating: Some Facts about Metabolism
• Triglycerides are complex molecules that contain glycerol (a soluble carbohydrate, also
called glycerine) combined with three fatty acids (stearic acid, oleic acid, and palmitic
acid).
• Glycerol (gliss er all)
• a substance (also called glycerine) derived from the breakdown of triglycerides, along
with fatty acids; can be converted by the liver into glucose
• Fatty Acid
• a substance derived from the breakdown of triglycerides, along with glycerol; can be
metabolized by most cells of the body except for the brain
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What Starts a Meal?
Signals from the Stomach
• The gastrointestinal system (especially the stomach) releases a peptide hormone called
ghrelin (Kojima et al., 1999).
• Ghrelin (grell in)
• a peptide hormone released by the stomach that increases eating; also produced by
neurons in the brain
• The name ghrelin is a contraction of GH releasin, which reflects the fact that this peptide
is also involved in controlling the release of growth hormone, usually abbreviated as GH.
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•Ghrelin is a potent stimulator of food intake, and it even stimulates thoughts about food.
•Schmid et al. (2005) found that a single intravenous injection of ghrelin not only
enhanced appetite in normal subjects—it also elicited vivid images of foods that the
subjects liked to eat.
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What Starts a Meal?
Signals from the Stomach
• Ghrelin secretion is suppressed when an animal eats or when an experimenter infuses
food into the animal’s stomach.
• Injections of nutrients into the blood do not suppress ghrelin secretion, so the release of
the hormone is controlled by the contents of the digestive system and not by the
availability of nutrients in the blood (Schaller et al., 2003).
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What Starts a Meal?
Signals from the Stomach
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Williams et al. (2003) operated on rats and installed devices similar to miniature blood-pressure cuffs
around the pylorus, the junction between the stomach and the duodenum.
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The duodenum is the uppermost part of the small intestine.
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Duodenum
• the first portion of the small intestine; attached directly to the stomach
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When a cuff was inflated, it would compress the pylorus and prevent the contents of the stomach from
leaving.
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Surprisingly, Williams and her colleagues found that an infusion of food into the stomach would not
suppress the secretion of ghrelin when the cuff was inflated.
•
However, when the pylorus was open, an infusion of food into the stomach, which could then reach the
small intestine, did suppress ghrelin secretion.
•
Thus, although the stomach secretes ghrelin, its secretion appears to be controlled by receptors present
in the upper part of the small intestine, not in the stomach itself.
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What Starts a Meal?
Metabolic Signals
• When (nonradioactive) 2-DG is given in large doses, it interferes with glucose metabolism
by competing with glucose for access to the mechanism that transports glucose through
the cell membrane and for access to the enzymes that metabolize glucose.
• Both hypoglycemia and 2-DG cause glucoprivation; that is, they deprive cells of glucose.
• And glucoprivation, whatever its cause, stimulates eating.
• Glucoprivation
• a dramatic fall in the level of glucose available to cells; can be caused by a fall in the
blood level of glucose or by drugs that inhibit glucose metabolism
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What Starts a Meal?
Metabolic Signals
• Hunger can also be produced by causing lipoprivation—depriving cells of lipids. More
precisely, they are deprived of the ability to metabolize fatty acids through injection of a
drug such as mercaptoacetate.
• Lipoprivation
• a dramatic fall in the level of fatty acids available to cells; usually caused by drugs
that inhibit fatty acid metabolism
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What Starts a Meal?
Metabolic Signals
• Novin, VanderWeele, and Rezek (1973) suggested that receptors in the liver can
stimulate glucoprivic hunger; when these neurons are deprived of nutrients, they cause
eating.
• The investigators infused 2-DG into the hepatic portal vein.
• Hepatic Portal Vein
• the vein that transports blood from the digestive system to the liver
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What Starts a Meal?
Metabolic Signals
• This vein brings blood from the intestines to the liver; thus, an injection of a drug into this
vein (an intraportal infusion) delivers it directly to the liver. (See Figure 12.14.)
• The investigators found that the intraportal infusions of 2-DG caused immediate eating.
• When they cut the vagus nerve, which connects the liver with the brain, the infusions no
longer stimulated eating.
• Thus, the brain receives the hunger signal from the liver through the vagus nerve.
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What Stops a Meal?
Intestinal Factors
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The duodenum controls the rate of stomach emptying by secreting a peptide hormone called
cholecystokinin (CCK).
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Cholecystokinin (CCK) (coal i sis toe ky nin)
• a hormone secreted by the duodenum that regulates gastric motility and causes the
gallbladder (cholecyst) to contract; appears to provide a satiety signal transmitted to the
brain through the vagus nerve
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This hormone receives its name from the fact that it causes the gallbladder (cholecyst) to
contract, injecting bile into the duodenum. (Bile breaks fats down into small particles so that
they can be absorbed from the intestines.)
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CCK is secreted in response to the presence of fats, which are detected by receptors in the
walls of the duodenum.
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In addition to stimulating contraction of the gallbladder, CCK causes the pylorus to constrict
and inhibits gastric contractions, thus keeping the stomach from giving the duodenum more
food.
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What Stops a Meal?
Intestinal Factors
• CCK does not act directly on the brain; instead, it acts on receptors located in the junction
between the stomach and the duodenum (Moran et al., 1989).
• South and Ritter (1988) found that the appetite-suppressing effect of CCK was abolished
by the application of capsaicin to the vagus nerve.
• Capsaicin, a drug extracted from chili peppers, destroys sensory axons in the vagus
nerve.
• This finding indicates that signals from CCK receptors are transmitted to the brain via the
vagus nerve.
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What Stops a Meal?
Intestinal Factors
• As we saw earlier in this chapter, secretion of ghrelin by the stomach provides a signal
that increases hunger.
• Once a meal begins and food starts to enter the duodenum, the secretion of ghrelin is
suppressed.
• The suppression of a hunger signal could well be another factor that brings a meal to its
end.
• Investigators have discovered an chemical produced by cells in the gastrointestinal tract
that appears to serve as an additional satiety signal.
• This chemical, peptide YY3–36 (PYY), is released by the small intestine after a meal in
amounts proportional to the calories that were just ingested (Pedersen-Bjergaard et al.,
1996).
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What Stops a Meal?
Long-Term Satiety: Signals from Adipose Tissue
• Researchers in several laboratories reported the discovery of the cause of the obesity
(Campfield et al., 1995; Halaas et al., 1995; Pelleymounter et al., 1995).
• A particular gene, called OB, normally produces a peptide hormone that has been given
the name leptin (from the Greek word leptos, “thin”).
• Leptin
• a hormone secreted by adipose tissue; decreases food intake and increases
metabolic rate, primarily by inhibiting NPY-secreting neurons in the arcuate nucleus
• Leptin is normally secreted by well-nourished fat cells. Because of a genetic mutation, the
fat cells of ob mice are unable to produce leptin.
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What Stops a Meal?
Long-Term Satiety: Signals from Adipose Tissue
• Leptin has profound effects on metabolism and eating, acting as an antiobesity hormone.
• If ob mice are given daily injections of leptin, their metabolic rate increases, their body
temperature rises, they become more active, and they eat less.
• As a result, their weight returns to normal. Figure 12.18 shows a picture of an untreated
ob mouse and an ob mouse that has received injections of leptin. (See Figure 12.18.)
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Brain Mechanisms
Hypothalamus
•
Melanin-Concentrating Hormone (MCH)
• a peptide neurotransmitter found in a system of lateral hypothalamic neurons that
stimulate appetite and reduce metabolic rate
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Orexin
• a peptide neurotransmitter found in a system of lateral hypothalamic neurons that
stimulate appetite and reduce metabolic rate
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Researchers refer to MCH and orexin as orexigens, “appetite-inducing chemicals.” Injections
of either of these peptides into the lateral ventricles or various regions of the brain induce
eating.
•
If rats are deprived of food, production of MCH and orexin in the lateral hypothalamus
increases (Qu et al., 1996; Sakurai et al., 1998; Dube, Kalra, and Kalra, 1999).
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Of these two orexigenic hypothalamic peptides, MCH appears to play the more important role
in stimulating feeding
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Brain Mechanisms
Hypothalamus
• An empty stomach, glucoprivation, or lipoprivation arises from detectors in the abdominal
cavity and brain stem.
• How do these signals activate the MCH and orexin neurons of the lateral hypothalamus?
• Part of the pathway involves a system of neurons that secrete a neurotransmitter called
neuropeptide Y (NPY), an extremely potent stimulator of food intake (Clark et al., 1984).
• Infusion of NPY into the hypothalamus produces ravenous, almost frantic eating.
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Brain Mechanisms
Hypothalamus
• In addition, NPY neurons send a projection of axons to the paraventricular nucleus (PVN),
a region of the hypothalamus where infusions of NPY affect metabolic functions, including
the secretion of insulin (Bai et al., 1985).
• Paraventricular Nucleus (PVN)
• a nucleus of the hypothalamus located adjacent to the dorsal third ventricle; contains
neurons involved in control of the autonomic nervous system and the posterior
pituitary gland
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Brain Mechanisms
Hypothalamus
• The terminals of hypothalamic NPY neurons release another orexigenic peptide in
addition to neuropeptide Y: agouti-related peptide, otherwise known as AGRP (Hahn et
al., 1998).
• Agouti-Related Protein (AGRP)
• a neuropeptide that acts as an antagonist at MC-4 receptors and increases eating
• Infusion of a very small amount of this peptide into the third ventricle of rats produces an
increase in food intake that lasts for six days (Lu et al., 2001).
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Brain Mechanisms
Hypothalamus
• I should briefly mention one other category of orexigenic compounds: the
endocannabinoids. (See Di Marzo and Matias, 2005, and Bellocchio, 2010, for reviews of
the evidence cited in this section.)
• One of the effects of the THC contained in marijuana is an increase in appetite—
especially for highly palatable foods.
• The endocannabinoids—whose actions are mimicked by THC—stimulate eating,
apparently by increasing the release of MCH and orexin.
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Obesity
• Obesity is a widespread problem that can have serious medical consequences.
• In the United States, approximately 67 percent of men and 62 percent of women are
overweight, which is defined as body mass index (BMI) of over 25.
• In the past twenty years, the incidence of obesity, defined as a BMI of over 30, has
doubled in the population as a whole and has tripled for adolescents.
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Obesity
Possible Causes
• Indeed, obese people already have elevated blood levels of leptin, and additional leptin
has no effect on their food intake or body weight.
• However, several investigators have suggested that a fall in blood levels of leptin should
be regarded as a hunger signal.
• That is, a low level of leptin increases the release of orexigenic peptides and decreases
the release of anorexigenic peptides.
• And as Flier (1998) suggests, people with a thrifty metabolism should show resistance to
a high level of leptin, which would permit weight gain in times of plenty.
• People with a spendthrift metabolism should not show leptin resistance, and should eat
less as their level of leptin rises.
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Obesity
Treatment
• Obesity is extremely difficult to treat; the enormous financial success of diet books, health
spas, and weight reduction programs attests to the trouble people have in losing weight.
• More precisely, many programs help people to lose weight initially, but then the weight is
quickly regained.
• Kramer et al. (1989) reported that 4 to 5 years after participating in a 15-week behavioral
weight-loss program, fewer than 3 percent of the participants managed to maintain the
weight loss they had achieved during the program.
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Obesity
Treatment
• Surgeons have become involved in trying to help obese people lose weight.
• The procedures they have developed (called bariatric surgery, from the Greek barys,
“heavy,” and iatrikos, “medical”) are designed to reduce the amount of food that can be
eaten during a meal or interfere with absorption of calories from the intestines.
• Bariatric surgery has been aimed at the stomach, the small intestine, or both.
• The most effective form of bariatric surgery is a special form of gastric bypass called the
Roux-en-Y gastric bypass, or RYGB.
• This procedure produces a small pouch in the upper end of the stomach.
• The jejunum (the second part of the small intestine, immediately “downstream” from the
duodenum) is cut, and the upper end is attached to the stomach pouch.
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Obesity
Treatment
• One important reason for the success of the RYGB procedure appears to be that it
disrupts the secretion of ghrelin.
• The procedure also increases blood levels of PYY (Chan et al., 2006; Reinehr et al.,
2006).
• Both of these changes would be expected to decrease food intake: A decrease in ghrelin
should reduce hunger, and an increase in PYY should increase satiety.
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Obesity
Treatment
• Some serotonergic agonists suppress eating. However, a drug used for this purpose,
fenfluramine, was found to have hazardous side effects (including pulmonary
hypertension and damage to the valves of the heart), so the drug was withdrawn from the
market in the United States (Blundell and Halford, 1998).
• Fenfluramine acts by stimulating the release of 5-HT. Another drug, sibutramine, has
similar therapeutic effects on eating—but a study of people who were taking the drug
found increased incidence of heart attacks and strokes, so this drug, too, was withdrawn
from the market (Li and Cheung, 2011).
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Anorexia Nervosa/Bulimia Nervosa
• Most people, if they have an eating problem, tend to overeat.
• However, some people, especially among adolescent women, have the opposite problem:
They eat too little, even to the point of starvation.
• This disorder is called anorexia nervosa.
• Anorexia Nervosa
• a disorder that most frequently afflicts young women; exaggerated concern with being
overweight that leads to excessive dieting and often compulsive exercising; can lead
to starvation
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Anorexia Nervosa/Bulimia Nervosa
• Another eating disorder, bulimia nervosa, is characterized by a loss of control of food
intake. (The term bulimia comes from the Greek bous, “ox,” and limos, “hunger.”)
• People with bulimia nervosa periodically gorge themselves with food, especially dessert
or snack food, and especially in the afternoon or evening.
• These binges are usually followed by self-induced vomiting or the use of laxatives, along
with feelings of depression and guilt.
• Bulimia Nervosa
• bouts of excessive hunger and eating, often followed by forced vomiting or purging
with laxatives; sometimes seen in people with anorexia nervosa
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Anorexia Nervosa/Bulimia Nervosa
• Episodes of bulimia are seen in some patients with anorexia nervosa.
• The incidence of anorexia nervosa is estimated at 0.5–2 percent; that of bulimia nervosa
at 1–3 percent.
• Women are ten to twenty times more likely than men to develop anorexia nervosa and
approximately ten times more likely to develop bulimia nervosa. (See Klein and Walsh,
2004.)
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Anorexia Nervosa/Bulimia Nervosa
Possible Causes
• Anorexia is a serious disorder.
• Five to ten percent of people with anorexia die of complications of the disease or of
suicide. Many anorexics suffer from osteoporosis, and bone fractures are common.
• When the weight loss becomes severe enough, anorexic women cease menstruating.
• Some disturbing reports (Artmann et al., 1985; Herholz, 1996; Kingston et al., 1996;
Katzman et al., 2001) indicate the presence of enlarged ventricles and widened sulci in
the brains of anorexic patients, which indicate shrinkage of brain tissue.
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Anorexia Nervosa/Bulimia Nervosa
Possible Causes
• Blood levels of NPY are elevated in patients with anorexia. Nergårdh et al. (2007) found
that infusion of NPY into the cerebral ventricles further increased the time spent running
in rats on a restricted feeding schedule.
• Normally, NPY stimulates eating (as it does in rats with unlimited access to food), but
under conditions of starvation, it stimulates wheel-running activity instead.
• The likely explanation for this phenomenon is that if food is not present, NPY increases
the animals’ activity level, which would normally increase the likelihood that they would
find food.
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Anorexia Nervosa/Bulimia Nervosa
Treatment
• Anorexia is very difficult to treat successfully.
• Cognitive behavior therapy, considered by many clinicians to be the most effective
approach, has a success rate of less than 50 percent and a relapse rate of 22 percent
during a 1-year treatment period (Pike et al., 2003).
• A meta-analysis by Steinhausen (2002) indicates that the success rate in treating
anorexia has not improved in the last fifty years.
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