Appetite, Satiety, Hormones & Neurotransmitters –

Links with Obesity –Theories of Obesity

P.K.Suresh M.Sc. (University of Madras, TN, India)

M.S.(SIUE, IL, USA), Ph.D.(University of Cincinnati, Ohio, USA) 
PDF (University of Texas at Austin, Austin, TX, USA)
PDF (Rutgers University, Piscataway, NJ, USA)
PROFESSOR HIGHER ACADEMIC GRADE 
SBST, VIT University, Vellore, Vellore Dt. 
PIN: 632014. MOB: +91-44-9444047684.
Landline:0416-2202474. 
e-mail: p.k.suresh@vit.ac.in;indian.ethos@gmail.com
 The Mystery of Obesity
• Obesity’s cause remains elusive
• Hunger
• Satiety
• Response to physiological need
• Chemical messengers
• Stomach hormone
• Ghrelin
• Stomach capacity
https://www.the-scientist.com/feature/the-enormity-of-obesity-50015
 The Appetite and its Control
• When you grab a snack or eat a meal, you may be aware only of your conscious mind
choosing to eat something.
• However, the choice of when and how much to eat may not be as free as you think—
deeper forces of physiology are at work behind the scenes.
• Seeking and eating food are matters of life and death, essential for survival.
• Understandably, therefore, the body’s appetite-regulating systems are skewed, tipping
in favor of food consumption. Hunger demands food.
• The signals that oppose food consumption, that is, signals for satiation and satiety, are
weaker and more easily overruled.
• Many signaling molecules, including hormones, help to regulate food intake; the
following sections name just a few.
To eat or not to eat –Your brain has the answer

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–Suppression of Eating
 Hunger
• Most people recognize hunger -strong, unpleasant sensation, the
response to a physiological need for food.
• Hunger -four to six hours after eating, after the food has left the
stomach and much of the nutrient mixture has been absorbed by the
intestine.
• The physical contractions of an empty stomach -hunger
signals, as do
• chemical messengers acting on or originating in the brain’s
hypothalamus

HYPOTHALAMUS – “central hub for energy and body weight regulation, and it can sense
molecules representing all three of the energy nutrients”.
Cutway Side View of the Brain Showing the Hypothalamus and Cortex
 Ghrelin
• The polypeptide ghrelin -a powerful hunger-stimulating hormone that opposes
weight loss.
• Ghrelin secreted by stomach cells but works in the hypothalamus and other brain
tissues to stimulate appetite.
• Among other things, ghrelin promotes efficient energy storage, contributing to
weight gain.
• Ghrelin may also promote sleep and a lack of sleep may trigger its release, helping
to explain why some sleep-deprived people report being extra hungry, eating
more food, and ultimately gaining weight.
• Ghrelin is just one of many hunger-regulating messengers that informs the brain of
the need for food.
• In fact, the brain itself produces a number of molecular messengers involved in
appetite regulation.
 Appetite
A person can experience appetite without hunger.
For example, the aroma of hot apple pie or the
sight of a chocolate butter cream cake after a big
meal can trigger a chemical stimulation of the
brain’s pleasure centers, thereby creating a desire
for dessert despite an already full stomach.
In contrast, a person who is ill or under stress may
physically need food but have no appetite.
Other factors affecting appetite
(1)Hunger outweighs satiety in the
(1) Appetite stimulants or depressants, other medical drugs.
(2) Cultural habits (cultural or religious acceptability of foods).
appetite
(3) Environmental control
conditions (people system.
often prefer hot foods in cold weather and vice versa).
(2)Hunger
(4) Hormones ishormones).
(for example, sex a physiologic response to
(5) Inborn appetites (inborn preferences for fatty, salty, and sweet tastes).
(6) Learnedan absence
preferences of food
(cravings for favorite in tothe
foods, aversion trying digestive
new foods, and eating
tract.
according to the clock).
(7) Social interactions (companionship, peer influences).Some disease states (obesity may be
(3)The stomach hormone ghrelin is
associated with increased taste sensitivity, whereas colds, flu, and zinc deficiency reduce taste
sensitivity).
one of many contributors to feelings
of hunger
 Satiation and Satiety—“Stop” Signals
• To balance energy in with energy out, eating behaviours must be counterbalanced
with ending each meal and allowing periods of fasting between meals.
• Being able to eat periodically, store fuel, and then use up that fuel between meals is
a great advantage.
• Relieved of the need to constantly seek food, human beings are free to dance, study,
converse, wonder, fall in love, and concentrate on endeavours other than eating.
• The between-meal interval is normally about 4 to 6 waking hours—about the
length of time the body takes to use up most of the readily available fuel—or 12 to
18 hours at night, when body systems slow down and the need is less.
• As is true for the “go” signals that stimulate food intake, a series of many
hormones and sensory nerve messages along with products of nutrient metabolism
send “stop” signals to suppress eating.
• Much more remains to be learned about these mechanisms.
 Satiation
 At some point during a meal, the brain receives signals that enough food has been eaten.
 The resulting satiation causes continued eating to hold less interest, and limits the size of the meal.
 Satiation arises from many organs:
▪ Sensations in the mouth associated with greater food intake trigger increased
satiation.
▪ Nerve stretch receptors in the stomach sense the stomach’s distention with a meal
and fire, sending a signal to the brain that the stomach is full.
▪ As nutrients from the meal enter the small intestine, they stimulate other receptor
nerves and trigger the release of hormones signaling the hypothalamus about the size and
nature of the meal.
▪ The brain also detects absorbed nutrients delivered by the bloodstream, and it
responds by releasing neurotransmitters that suppress food intake. Together, mouth
sensations, stomach distention, and the presence of nutrients trigger nervous and hormonal
signals to inform the brain’s hypothalamus that a meal has been consumed. Satiation occurs;
the eater feels full and stops eating.
 Did My Stomach Shrink?
• Changes in food intake cause rapid adaptations in the body.

• A person who suddenly eats smaller meals may feel extra hungry for a few days, but
then hunger may diminish for a time.

• During this period, a large meal may make the person feel uncomfortably full, partly
because the stomach’s capacity has adapted to a smaller quantity of food.

• A dieter may report “My stomach has shrunk,” but the stomach has simply adjusted to
smaller meals. At some point in food deprivation, hunger returns with a vengeance and
can lead to bouts of extensive overeating. Just as quickly, the stomach’s capacity can
adapt to larger meals until moderate portions no longer satisfy. This observation may
partly explain the increasing U.S. calorie intakes: popular demand and food industry
marketing have led to larger and larger food portions, while stomachs across the nation
 Satiety
• After finishing a meal, the feeling of satiety continues
to suppress hunger over a period of hours, regulating
the frequency of meals.
• Hormones, nervous signals, and the brain work in
harmony to sustain feelings of fullness.
• At some later point, signals from the digestive tract
once again sound the alert that more food is needed.
 Leptin
• Leptin, one of the adipokine hormones, is produced in direct proportion to body fatness.
• A gain in body fatness stimulates leptin production. Leptin travels from the adipose tissue
via the bloodstream to the brain’s hypothalamus, where it promotes the release of
neurotransmitters that both suppress appetite and increase energy expenditures and,
ultimately, body fat loss.
• A loss of body fatness, in turn, brings the opposite effects— suppression of leptin
production, increased appetite, reduced energy expenditure, and accumulation of body fat.
• Leptin operates on a feedback mechanism—the fat tissue that produces leptin is ultimately
controlled by it. In experiments, obese rats develop both insulin resistance and leptin
resistance— the rats fail to respond to leptin’s appetite-suppressing effects.
• In a rare form of human obesity arising from an inherited inability to produce leptin, giving
leptin injections quickly reverses both obesity and insulin resistance.
• More commonly, obese people produce plenty of leptin but are resistant to its effects;
giving more leptin does not reverse their obesity.
Leptin
Leptin –Mechanism to regulate weight

https://coledrotman.files.wordpress.com/2013/07/leptin2.gif
 Role of Brain Neurotransmitters
• Neurotransmitters govern the body’s response to
starvation and dietary intake
• Decreases in serotonin and increases in neuropeptide Y
are associated with an increase in carbohydrate appetite
• Neuropeptide Y increases during deprivation; may account
for increase in appetite after dieting
• Cravings for sweet high-fat foods among obese and
bulimic patients may involve the endorphin system
 Transmitters regulating Body Weight

• Norepinephrine and dopamine—released by

sympathetic nervous system in response to
dietary intake
• Fasting and semistarvation lead to decreased
levels of these neurotransmitters—more
epinephrine is made and substrate is mobilized.
 Hormones and Weight
• Hypothyroidism may diminish adaptive
thermogenesis
• Insulin resistance may impair adaptive
thermogenesis
• Leptin is secreted in proportion to percent
adipose tissue and may regulate (decrease)
appetite
 Energy Nutrients and Satiety
• The composition of a meal seems to affect satiation and satiety, but the
relationships are complex. Of the three energy-yielding nutrients, protein
seems to have the greatest satiating effect during a meal.
• Therefore, including some protein in a meal—even a glass of milk—can
improve satiation and possibly even decrease energy intake at the next
meal.
• Many carbohydrate-rich foods, such as those providing slowly digestible
carbohydrate and soluble fiber, also contribute to satiation and satiety.
• These foods tend to hold blood glucose and insulin steady between meals,
minimizing dips in blood glucose that are sensed by the brain, which
responds by increasing hunger to restore blood glucose to normal.
 Energy Nutrients and Satiety
• Added sugars in beverages, in contrast, may not suppress
appetite but increase caloric intake.
• Soluble fibers and digestion-resistant starch also may
support colonies of bacteria in the colon that have been
associated with leanness in some studies.
• Finally, fat, famous for triggering a hormone that
contributes to long-term satiety, goes almost unnoticed
by the appetite control system during consumption of a
meal.
 Energy Nutrients and Satiety
• Researchers have also reported increased satiety from foods high in water and even
from foods that have been puffed up with air.
Satiation ends a meal when the nervous and
• Boredom and sameness of taste and texture also create a sort of sensory-specific
hormonal
satiety—the initial signals
pleasure of inform the brain
eating a particular that bite
food diminishes enough
after bite, and
this decline in liking of a food is a common reason why people stop eating.
food has been eaten.
• As dieters await news of dietary tactics against hunger, researchers have not yet
Satiety
identified anypostpones eating
one food, nutrient, until theeven
or attribute—not next meal. is especially
protein—that
effective for weight loss and its maintenance.
The adipokine leptin suppresses the appetite and
regulates body fatness. Protein, carbohydrate,
and fat play various roles in satiation and satiety.
Hunger, Appetite, Satiation & Satiety
 Inside-the-Body Causes of Obesity
•Metabolic theories
• Variations in ease of body fat gain or loss
• Variety of theories
•Genetics
• Influence tendency to gain weight or stay lean
• Environmental factors
 Inside-the-Body Theories of Obesity
• Findings about appetite regulation, the “energy in” side of the body weight
equation, do not fully explain why some people gain too much body fat and others
stay lean.
• When given a constant number of excess calories over a period of weeks or
months, some people gain many pounds of body fat, but other people gain far
fewer.
• The former seem to use every calorie with great metabolic efficiency, while others
may expend calories more freely.
• Many theories have emerged to explain these mysteries of obesity in terms of
metabolic function and energy expenditure—this section just touches the surface
of a few of them.
• And whenever discussions turn to metabolism, topics in genetics follow closely
behind
 Set-Point Theory
 Like a room’s thermostat, the brain and other organs constantly monitor
body conditions and respond to slight fluctuations in such essential
functions as blood glucose, blood pH levels, and body temperature to
maintain them within a narrow range of a physiological set point.
 The set-point theory of obesity holds that, to a degree, this may also be
true for body weight.
 After weight gains or losses, the body adjusts its metabolism somewhat
in the direction of restoring the original weight.
 If weight is gained slowly over time, however, a new set point may be
established and defended.
 Many debates surround the set-point theory of weight regulation.
 Thermogenesis
 Some people tend to expend more energy in metabolism than
others. Could that explain obesity?
 The body’s enzymes “waste” a small percentage of energy as
heat in a process called thermogenesis.
 Some enzymes expend copious energy in thermogenesis,
producing heat but performing no other useful work.
 As more heat is radiated away from the body, more calories are
spent, and fewer calories are available to be stored as body fat.

More the heat produced, greater the calories spent

• In a remote Buddhist monastery in Northern India, a group of monks sit calmly,
lightly dressed and unaffected by the shockingly low temperatures of their
surroundings (40 degrees Fahrenheit / 4 degrees Celcius). They are then draped with
ice-cold, wet sheets of fabric. In conditions that would not only cause the average
person to shiver uncontrollably, but could even result in death, the monks remain
unperturbed.
• If that’s not amazing enough, the wet sheets soon begin to steam and after
approximately 1 hour are even completely dry.
• How is this possible? The monks were using a yoga technique known as g Tum-mo,
which allowed them to enter a state of deep meditation and significantly raise their
body heat, some as much as 17 degrees (Fahrenheit) in their fingers and toes.
https://www.buzzworthy.com/monks-raise-body-temperature/
• After the first sheets were dry, they were replaced with new wet sheets
by attendants. Each monk was required to dry 3 sheets over the course of
several hours. In other contests held during cold Himalayan nights, the
person who dries the most sheets before dawn is considered the winner.

• The heat generated through g Tum-mo is only a by product of a process

designed to correct misconceptions of reality as defined by Buddhism.
Herbert Benson, an associate professor of Medicine at Harvard University
who has been studying g Tum-mo for over 20 years, is a firm believer in
the healing power of such practices.
https://www.buzzworthy.com/monks-raise-body-temperature/
”The study of advanced forms of meditation like g Tum-mo can uncover capacities
that will help us to better treat stress-related illnesses. More than 60% of visits to
physicians in the United States are due to stress related problems, most of which are
poorly treated by drugs, surgery, or other medical procedures.”
The two aspects of g Tum-mo meditation that lead to temperature increases are
‘Vase breath’ and concentrative visualisation. ‘Vase breath’ is a specific breathing
technique which causes thermogenesis, a process of heat production. The other
technique, concentrative visualisation, involves focusing on a mental image of flames
along the spinal cord in order to prevent heat loss. Scientists at Harvard see the
phenomenon as a profound example of the mind’s ability to influence the body.

https://www.buzzworthy.com/monks-raise-body-temperature/
 Thermogenesis
• One tissue extraordinarily gifted in thermogenesis is brown
adipose tissue (BAT).
• BAT, a well-known heat-generating tissue of animals and human
infants, has been identified in adult human subjects, too.
• The subjects with the greatest body fatness in these studies had
the least BAT.
• Intriguingly, a chemical released during muscular work appears
to trigger a normally dormant type of adipose cell to act more
like BAT metabolically, but the significance of this finding to
weight management is unknown.
 Thermogenesis
Is it wise, then, to try to step up thermogenesis to
assist in weight loss? Probably not. In rats, the
rate of thermogenesis has no effect on overall
energy expenditure or body fatness.
Also, at a level not far above normal, energy-
wasting activity causes cell death. Sham
“metabolic” diet products may claim to increase
thermogenesis, but no tricks of metabolism can
produce effortless fat loss.
 Genetics & Obesity
• If genes carry the instructions for making enzymes, and enzymes
control energy metabolism, then genetic variations might reasonably
be expected to explain why some people get fat and some stay lean.
Indeed, genomic researchers have identified multiple genes likely to
play roles in obesity development but have not so far identified a
single genetic cause of common obesity.
• Inherited genes clearly do influence body weight, however. For
someone with at least one obese parent, the chance of becoming
obese is estimated to fall between 30 and 70 percent.
• Complex relationships exist among the many genes related to energy
metabolism and obesity, and they each interact with environmental
factors, too, even before birth.
 Genetics & Obesity
For example, research suggests that over- or
undernutrition of a pregnant female may alter genetic
activities of a developing fetus in ways that increase the
likelihood of obesity later in life.

Even though an individual’s genetic inheritance and

early influences may make obesity likely, the disease of
obesity cannot develop unless the environment—factors
that lie outside the body—provides the means of doing
so.
 Outside-the-Body Causes of Obesity

• External cues to overeating

• Available foods
• Human sensations
• Larger portions
• Physical inactivity
• Nonexercise activity thermogenesis (NEAT)
• Inactivity epidemic
• Sitting still and death from heart disease
 Outside-the-Body Theories of Obesity
• Food is a source of pleasure, and pleasure drives behaviour .
• Being creatures of free will, people can easily override
satiety signals and eat whenever they wish, especially when
tempted with delicious treats in large servings.
• People also value physical ease and seek out labor-savers,
such as automobiles and elevators.
• Over past decades, the abundance of palatable food has
increased enormously, while the daily demand for physical
activity for survival has all but disappeared.
 Environmental Cues to Overeating
• Here’s a common experience: a person walks into a food store feeling
not particularly hungry but, after viewing an array of goodies, walks out
snacking on a favorite treat.
• A classic experiment showed that rats, known to precisely maintain
body weight when fed standard chow, overeat and rapidly become
obese when fed “cafeteria style” on a variety of rich, palatable foods.
• When offered a delicious smorgasbord, people may do likewise, often
without awareness.
• Like the rats, they respond to external cues. With around-the-clock
access to rich palatable foods, we eat more and more often than in
decades past—and energy intakes have risen accordingly.
 Environmental Cues to Overeating
• Overeating also accompanies complex human
sensations such as loneliness, yearning, craving,
addiction, or compulsion.
• Any kind of stress can also cause overeating and
weight gain.(“What do I do when I’m worried? Eat.
• What do I do when I’m concentrating? Eat!”)
• People who are overweight or obese may be
especially responsive to such external cues.
 Environmental Cues to Overeating
• People also overeat in response to large portions of food. In a classic study,
moviegoers ate proportionately more popcorn from large buckets than from
small bags.
• In a wry twist, researchers dispensed large and small containers of 14-day-
old popcorn to moviegoers who, despite complaining of the staleness, still
ate more popcorn from the larger container.
• Even superior education in nutrition doesn’t stop the phenomenon.
• Nutrition graduate students were invited to a party and offered snack mix
from big and small bowls.
• As predicted, even they ate bigger portions from the bigger bowls.
• Portion sizes have increased steadily over past decades, and so have calorie
intakes and body fatness
 Is Our Food Supply Addictive?
• People often equate overeating with an addiction.
• Right away, it should be said that foods, even highly
palatable foods, are not comparable to psychoactive
drugs in most respects.
• Yet, emerging evidence supports certain similarities
between the brain’s chemical responses to both.
• Pleasure-evoking experiences of all kinds cause brain
cells to release the neurotransmitter dopamine, which
stimulates the reward areas of the brain.
 Is Our Food Supply Addictive?

• The result is feelings of pleasure and desire that

create a motivation to repeat the experience.
• Paradoxically, with repeated exposure to a chemical
stimulus (say the drug cocaine) over time, the brain
reduces its dopamine response, reducing feelings of
pleasure.
• Soon, larger and larger doses are needed to achieve
the desired effect—addiction.
 Is Our Food Supply Addictive?
• Brain scans reveal reduced brain dopamine activity in people
addicted to cocaine or alcohol. In a classic study, brain scans also
revealed dopamine reductions in the brains of obese people.
• This suggests that, similar to an addiction, once these changes
are in place, obese people may need more and more delicious
food to satisfy their desire for it. Taking the idea one step
further, it is plausible that our highly palatable, fat- and sugar-
rich food supply could be causing lasting changes in the brain’s
reward system and making overeating and weight gain likely. It
happens reliably in the brains of rats fed cookies, cheese, sugar,
and other tasty items, and it may happen in people, too
 Is Our Food Supply Addictive?
• Other explanations exist.
• It may be that consciously restricting intakes of
delicious foods increases the desire for them.
• It may also be that some people are more inclined
to “throw caution to the wind” and indulge in treats
whenever they present themselves.
• Future research must untangle these threads before
the truth is known.
 Physical Inactivity
 Many people may be obese not because they eat too much, but because they move
too little—both in purposeful exercise and in the activities of daily life.
 Sedentary screen time has all but replaced outdoor play for many people. This is a
concern because the more time people spend in sedentary activities, the more likely
they are to be overweight—and to incur the metabolic risk factors of heart disease
(high blood lipids, high blood pressure, and high blood glucose).
 Most people also work at sedentary jobs.
 A hundred years ago, 30 percent of the energy used in farm and factory work came
from human muscle power; today, only 1 percent does. The same trend follows at
home, at work, at school, and in transportation. The more hours spent sitting still,
the higher the risk of dying from heart disease and other causes.
 Can Your Neighborhood Make You Fat?

 Experts urge people to “take the stairs instead of the elevator” or “walk or
bike to work.”
 These are good strategies: climbing stairs provides an impromptu workout,
and people who walk or ride a bicycle for transportation most often meet
their needs for physical activity.
 Many people, however, encounter barriers in their built environment that
prevent such choices.
 Few people would choose to walk or bike on roadways that lack safe
sidewalks or marked bicycle lanes, where vehicles speed by, or where the air
is laden with toxic carbon monoxide gas or other pollutants from gasoline
engines.
 Can Your Neighborhood Make You Fat?
 Few would choose to walk up flights of stairs in inconvenient, stuffy,
isolated, and unsafe stairwells in modern buildings.
 In contrast, people living in safe, attractive, affordable neighborhoods
with safe biking and walking lanes, public parks, and freely available
exercise facilities use them often—their surroundings encourage physical
activity.
 In addition, residents of many low-income urban and rural areas lack
access to even a single supermarket.
 Often overweight and lacking transportation, residents of these so-called
food deserts have limited access to the affordable, fresh, nutrient-dense
foods they need.
Can Your Neighborhood Make You Fat?
Instead, they shop at local convenience stores
and fast-food places, where they can purchase
mostly refined packaged sweets and starches,
sugary soft drinks, fatty canned meats, or fast
foods, and they often have an eating pattern that
predicts nutrient deficiencies and excesses along
with the high rates of obesity and type 2
diabetes.
Can Your Neighborhood Make You Fat?
• In truth, in most neighborhoods across the United States,
the most accessible, affordable, and tempting foods and
▪ Make beverages
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activity good-tasting,
an integral and routineinexpensive fare
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life. from fast-food restaurants, and it takes a great deal of
attention, planning, and time to “go against the
▪ Make healthy foods and beverages available everywhere—create flow” to
keep calorie intakes reasonable. Today, only about a third
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 Can Your Neighborhood Make You Fat?
• Accomplishing any one of these goals on its own might speed up
progress in preventing obesity, but if all these goals are realized, their
effects will be powerful allies in the nationwide struggle to regain
control over weight and health.
• Such changes require efforts from leaders at all levels and citizenry
across all sectors of society working with one goal: improving the
health of the nation.
• Until these changes occur, the best way for most people to attain a
healthy body composition boils down to control in three areas: diet,
physical activity, and behavior change. Later sections focus on these
areas, while the next section delves into the details of how, exactly,
the body loses and gains weight.
 Achieving and Maintaining a Healthy Body Weight

• Before setting out to change your body weight, think about your
motivation for doing so.
• Many people strive to change their weight, not to improve health, but
because their weight fails to meet society’s ideals of attractiveness.
• Unfortunately, this kind of thinking sets people up for
disappointment.
• The human body is not infinitely malleable. Few overweight people
will ever become rail-thin, even with the right eating pattern, exercise
habits, and behaviors. Likewise, most underweight people will remain
on the slim side even after spending much effort to put on some heft.