PHYSIOLOGY

2. PHYSIOLOGICAL BASIS OF EATING

We require energy and nutrients for the functioning of our body. And these nutrients in our body
come mostly from what we eat. Now what we eat and how much we eat mostly depends on hunger.
Hunger is a psychological state defined by a desire to eat.

There are many ways in which the body reacts to the need for eating or the basis of hunger. Our
stomachs contract when they are empty, hence one can experience hunger pangs. Chemical
messages are transmitted to the brain and act as a signal to stimulate eating behaviour. Also,
another reason is when our blood glucose levels drop, the pancreas and liver produce several
chemical signals that stimulate hunger and initiate eating behaviour.

Feeding centres of the brain

The hypothalamus is a region of the brain that plays a critical role in feeding regulation. It has been
revealed by various physiological experiments that the feeding-regulating centre is confined to
the ventromedial hypothalamus, lateral hypothalamus (LH) and arcuate nucleus/ infundibular
nucleus (ARC).

Internal cues for feeding

Glucose based cue/ Glucostatic theory
Mayer proposed that decreased glucose utilization, which was detected by the brain at
glucosensitive sites, in unspecified locations, represented the stimulus for meal initiation. The
glucostatic theory of hunger postulated that reduced glucose utilization in these critical brain regions
leads to perception and expression of hunger. He also argued that increased glucose utilization in
these same glucosensitive sites leads to decreased hunger and the cessation of eating.

The glucostatic theory, in its original and simplest form, assumes that eating behavior is controlled in
large part by the level of blood glucose in the body.

The first person to propose this theory was Jean Mayer, who is better known today as a nutrition
expert. Originally, Mayer suggested that the hypothalamus contains receptors sensitive to the
glucose levels in the the blood and that fluctuations in these levels determine whether eating is
triggered or suppressed. When glucose levels fall below optimum, he theorized, eating triggered;
when glucose levels are again above optimum, eating ceases.

In this case, too, there is evidence for and against the theory. The strongest argument in its favor is
the importance of glucose to brain activity. The slightest deficiency of glucose, which can come
about as the result of missing several meals in a row or of taking an overdose of insulin, is sufficient
to impede neural activity in the brain and produce dizziness, a coma, and if the deficiency lasts for a
sufficient amount of time, even death.
But the glucostatic theory runs into problems when the eating behavior of diabetics is considered:
Diabetes mellitus (not to be confused with diabetes insipidus) is caused by a deficiency of insulin, a
hormone released by the pancreas. Diabetics characteristically have a high level of glucose in thes
blood (hyperglycemia), which would mean, according to the glucostatic theory, that they would
never feel hungry. This, of course, isn't true (Diabetic are generally in a constant state of hunger.
Mayer has since revised his theory. The key to understanding this revision is the recognition that
glucose must pass into cells before it is metabolize. Maintaining the basic premise of his original
theory-namely, that eating regulated by glucose levels-Mayer has since shifted his emphasis from
glucose levels in the blood to glucose levels in the cells, contending that the later, not the former,
controls eating.

This revised theory explains why diabetics are constantly hungry despite the high glucose levels in
their blood. The main effect of insulin s to change the permeability of the cell membrane, making it
receptive to the flow of glucose. A shortage of insulin in the body produces a high degree of glucose
in the blood but little glucose in the cells. Hence, according the revised theory, diabetics are in a
constant state of hunger because the glucose levels in the cells remain low and low cell glucose is
the signal for hunger.

Experimental support for the glucostatic theory

In support of the theory, Albert Stunkard and H. Wolf , using human subjects, reported data which
suggest that as glucose levels in brain cells increase, hunger decreases. Their procedure (originally
suggested by Mayer) was indirect but effective: they drew blood from arteries entering the brain
and from veins leaving the brain, and they took the difference in glucose levels in the two blood
samples -as a measure of the amount of glucose that presumably was taken up by the cells in the
brain. They found that when a large difference in glucose existed between arterial and venous blood
(i.e., when the brain cells presumably took up large amounts of glucose) the subjects reported
feelings of satiation. And when small difference n glucose existed the subjects reported feelings of
hunger.

Lipid based signal/ Lipostatic theory

The lipostatic theory was originally advanced by George Kennedy in 1953 and was later elaborated
on by Philip Teitelbaum.

In brief the theory holds that some index of weight, such as fat deposits or fat-related chemicals is
the signal that regulates food intake.

Animals regulate eating according to their weight. If subjected to force feeding and made fat, they
will stop eating, if deprived of food and made skinny, they will start eating.

According to the homeostatic model, the brain (specifically, the hypothalamus) is thought to act as a
kind of scale that constantly weighs the animal by monitoring a correlate of weight traveling in the
blood. When weight or some correlate thereof rises above optimum, eating stops; when weight
drops below optimum, eating starts.
Teitelbaum arrived at the lipostatic theory mainly through his detailed observations of the
hyperphagia (overeating and obesity) syndrome that ensues following lesions in the ventromedial
hypothalamus.

He noted that hyperphagia is marked by two distinct behavioral phases.

First, the animal, immediately after the lesion is made, behaves as if determined to eat itself to
death, a period referred to as the dynamic phase. Second, after several weeks of incessant
overeating, the animal’s food intake returns to slightly above normal, a period called the static
phase.

Once the animal becomes obese, often tripling its normal weight during the dynamic phase, it stops
excessive overeating and eats enough during the static phase to maintain its new heavy weight.

If the hyperphagic data are viewed within the framework of the homeostatic model, it might be
argued that the destruction of the ventromedial hypothalamus has not really destroyed homeostasis
(i.e., the optimum level) but merely reset it at a higher level in effect, the lesion has lowered the
sensitivity of the receptors in the ventromedial hypothalamus, thereby calling for a compensatory
increase in the stimulation needed to turn off eating.

But a question still remains. What signal must be increased to compensate for the dampened
sensitivity? In other words, what food-related signal is present in excess in the obese ventromedially
lesioned animal that is not found in excess in the normal animal? The answer according to the
lipostatic theory is weight-specifically, a signal in the blood that is correlated with weight, such as
free fatty acid.

To test the theory that weight or some correlate thereof is the signal by which the ventromedial
hypothalamus inhibits eating, Teitelbaum conducted a series of experiments evaluating the
relationship between weight signal and the function of the ventromedial hypothalamus. A rat made
fat by a lesion in the ventromedial hypothalamus weighs from 500 to 1,500 grams. According to
Teitelbaum's lipostatic theory, this weight (or some signal of it) is necessary to stimulate the dulled
ventromedial hypothalamus to inhibit eating. It should follow that if the obese rat is forced to gain
even more weight, the weight-related signal should be present in excess, the dulled ventromedial
hypothalamus should be overstimulated by the excess weight signal, and paradoxically, the
superobese animal should stop eating. In fact, it should stop eating until its weight returns to the
original level of obesity (500 to 1,500 grams).

Teitelbaum confirmed this prediction. First, he made animals obese by lesioning the ventromedial
hypothalamus. Then he forced the animals to eat and gain weight beyond their obese level by
training them to eat in order to avoid shock. He found that when animals made superobese in this
way were allowed to eat freely again, they refrained from eating until they lost weight and returned
to their normal obese state (500 grams). Apparently, a weight- related signal is critical for controlling
eating.

Determinants of Satiety
When we consume any nutritive product (i.e., foods or drinks), those ingested nutrients provide
signals that act to reduce our desire to eat and drink for some time after consumption. This is
captured by the concept of satiety, the state of inhibition of appetite post-ingestion.
Likewise, our desire to eat decreases during a meal, and the processes which lead to that reduction
are referred to as satiation. Simplistic models have traditionally interpreted satiation and satiety
simply as a function of ingested nutrients.

However, there is now an abundance of evidence that both satiation and satiety are influenced by
multiple factors, including beliefs and information about products prior to ingestion, the specific
sensory characteristics of the product experienced during ingestion, and the volume, weight,
macronutrient profile, and energy density of the consumed product and the social context in which
food is ingested.

Thus satiation and satiety are viewed as the product of a cascade of signals which interact to
generate the overall satiety state.

Expectations about how filling a product will be modifies portion size selection and influences
subsequent satiety.

Sensory cues such as oral processing time and flavor intensity modify satiation, while liking for the
consumed product, but not unrelated products, decreases.

Once ingested, gut-based signals, including the release of satiety hormones stimulated by nutrient
sensing, interact with cognitive and sensory cues from ingestion to produce satiety.

But how much individuals respond to these cues varies, with weak satiety responsiveness a risk for
subsequent weight gain. Overall, satiation and satiety are highly complex phenomena, but our
increased understanding of this complexity paves the way for the food products of the future.

Neural and hormonal mechanisms of eating

The body has two mechanisms for regulating food intake: short-term and long-term.

Short-term regulation attempts to take in sufficient energy to balance what is being expended
(glucose levels). Long-term regulation is directed toward storing away sufficient energy (weight
gain).

Short-term food intake can impact blood sugar and blood pressure, while long-term food intake can
lead to weight gain and other metabolic issues.

Here are some short-term and long-term effects of food intake:

• Short-term

Eating too much food can cause discomfort in the short term. Fast food can impact blood sugar and
blood pressure, increase inflammation, and may mean an individual does not eat enough necessary
nutrients.

• Long-term

Eating too much food long term can lead to weight gain, along with other metabolic issues such as
insulin and leptin resistance, high triglycerides and increased risk for obesity and diabetes. A diet rich
in fast food could lead to issues with digestion, immunity, inflammation, heart health, obesity, and
more.
Orbito frontal cortex
The orbitofrontal cortex (OFC) is a region of the brain in the frontal lobe, located just above the
orbits (eye sockets). It plays a crucial role in decision-making, reward processing, and sensory
integration, making it a key player in modulating hunger and food-related behaviors.

Role of the Orbitofrontal Cortex in Hunger:

1. Integration of Sensory Inputs

o The OFC processes sensory information, such as taste, smell, and visual cues, that
contribute to the perception of food's palatability and desirability.

o It helps evaluate food rewards, influencing how appealing a particular food is based
on its sensory characteristics.

2. Reward Processing and Food Preferences

o The OFC is involved in assigning reward value to food:

▪ It helps determine which foods are more rewarding based on current needs
(e.g., hunger state) and past experiences.

▪ This dynamic evaluation adjusts preferences—for example, making high-

calorie foods more appealing when hungry.

The Arcuate nucleus (ARC)

The arcuate nucleus is a critical structure in the hypothalamus that plays a central role in regulating
hunger and energy balance.

It serves as a critical hub for controlling hunger, satiety, and energy balance by integrating hormonal,
nutrient, and neural signals from the body.

The arcuate nucleus is strategically located near the blood-brain barrier, allowing it to sense
peripheral hormone levels (like leptin, ghrelin, and insulin).

The arcuate nucleus contains two primary types of neurons with opposite roles in appetite
regulation:

Orexigenic Neurons (Hunger-Promoting):

• Release Neuropeptide Y (NPY) and Agouti-Related Peptide (AgRP).

• NPY is one of the most potent stimulators of appetite.

• Activated by ghrelin, a hunger hormone released from the stomach during fasting.

Anorexigenic Neurons (Satiety-Promoting):

• Release Pro-opiomelanocortin (POMC)

 • POMC is cleaved to produce α-melanocyte-stimulating hormone (α-MSH), which activates
melanocortin receptors n the ventromedial hypothalamus to suppress appetite.

• Activated by leptin and insulin, which signal energy sufficiency.

Ghrelin
Ghrelin, often called the "hunger hormone," plays a significant role in regulating appetite and
energy balance. It is primarily secreted by the stomach and to some extent by the small
intestine, pancreas, and brain. Here’s how it connects to hunger:

Key Points about Ghrelin and Hunger:

o Ghrelin levels rise before meals, signaling hunger to the brain, and decrease after
eating.

o It acts on the hypothalamus, particularly the arcuate nucleus in the orexinergic

neurons, to stimulate the sensation of hunger.

o Ghrelin helps the body manage energy storage by promoting food intake during
periods of energy deficit.

o Beyond hunger, ghrelin influences reward-driven eating, increasing cravings for

high-calorie or palatable foods.

o Ghrelin works oppositely to leptin, another hormone that signals satiety and reduces
hunger. This balance between ghrelin and leptin is crucial for maintaining a healthy
body weight.

Insulin
Insulin, a hormone secreted by the pancreas in response to rising blood glucose levels, plays a
significant role in regulating hunger and energy balance, in addition to its primary function of
glucose metabolism. In the context of hunger, insulin acts on the brain, particularly the
hypothalamus, to influence food intake and energy homeostasis.

Role of Insulin in Hunger Regulation:

1. Central Effects on the Brain:

o Insulin crosses the blood-brain barrier and binds to insulin receptors in the
hypothalamus, particularly in the arcuate nucleus (ARC).

o It influences two key neuronal populations:

▪ Inhibits orexigenic (hunger-promoting) neurons: Reduces activity of

NPY/AgRP neurons, which decreases hunger.

▪ Activates anorexigenic (satiety-promoting) neurons: Enhances activity of

POMC/CART neurons, signaling fullness and reducing food intake.
 Leptin
Leptin is a hormone primarily secreted by adipocytes (fat cells) that plays a pivotal role in
regulating long-term food intake and energy homeostasis. It acts as a key signal to the brain,
providing information about the body's energy stores and influencing hunger and satiety.

Leptin and Long-Term Food Intake Regulation

1. Secretion and Circulation:

o Leptin levels in the blood are proportional to the amount of body fat. More fat leads
to higher leptin levels, while weight loss reduces leptin production.

o It circulates in the bloodstream and crosses the blood-brain barrier to act on

receptors in the brain.

2. Leptin Receptors (LEPR):

o Leptin binds to its receptors, which are highly expressed in the arcuate nucleus
(ARC) of the hypothalamus.

o Key target neurons:

▪ Inhibits orexigenic neurons: Suppresses neuropeptide Y (NPY) and Agouti-

related peptide (AgRP), which promote hunger.

▪ Activates anorexigenic neurons: Stimulates POMC (pro-opiomelanocortin)

neurons, leading to the release of α-MSH, which suppresses appetite.

3. Homeostatic Feedback Loop:

o High body fat → Increased leptin → Decreased hunger and increased energy
expenditure.

o Low body fat → Decreased leptin → Increased hunger and reduced energy
expenditure.

o This feedback system helps maintain stable body weight over the long term.

Refer this video explaining hunger mechanism in a full cycle

[Link]

Palatability
Palatability is a measure of how pleasant a food or drink tastes and how it affects behavior,
particularly the drive to eat. It's a hypothetical construct that accounts for the sensory properties of
food, such as its taste, smell, texture, sound, and sight.
Palatability is closely related to energy density, with high energy-dense foods being more
palatable. This can lead to increased food intake and a higher risk of over-consumption. For example,
people may choose French fries over fresh vegetables because they are more palatable.

Role of opioids
The endogenous opioid system is a key player in the brain's response to highly palatable foods, such
as those rich in sugar and fat.

• Opioid System:

o Endogenous bind to opioid receptors in the brain to modulate pleasure and reward.

o Opioids are heavily involved in the hedonic (pleasure-driven) aspects of eating.

• Role in Palatability:

o Activation of opioid receptors in the nucleus accumbens (part of the brain's reward
system) enhances the pleasure derived from palatable foods.

o Opioids increase liking responses to sweet, fatty, or otherwise rewarding foods,

making them more desirable.

o Blocking opioid receptors (e.g., with drugs like naloxone) reduces food intake of
highly palatable foods, but not bland or unappealing foods.

Role of GABA
Gamma-Aminobutyric Acid (GABA), the brain's primary inhibitory neurotransmitter, also plays a
significant role in palatability and feeding behavior.

• GABA and Feeding:

o GABAergic neurons in the hypothalamus and other brain regions regulate hunger
and satiety by modulating neural circuits involved in food intake.

o GABA in areas like the lateral hypothalamus (LH) influences appetite, particularly for
palatable foods.

• Enhancement of Palatability:

o GABAergic signaling enhances the motivation to consume palatable foods by

suppressing inhibitory signals from satiety centers, allowing for continued
consumption despite physiological satiety.

o GABA interacts with the opioid system to amplify the rewarding effects of palatable
foods.

Taste Aversion Learning

Taste aversion learning is a survival mechanism through which animals (including humans) learn to
avoid foods associated with negative experiences, such as illness or discomfort.

• Mechanism:

o If consuming a food is followed by nausea or sickness, the brain forms an association

between the food and the adverse outcome.
 o This is mediated by the amygdala, insula, and gustatory cortex, which integrate
sensory and emotional components of the experience.

• Role in Palatability:

o Taste aversion reduces the palatability of foods linked to negative outcomes, even if
they were previously enjoyed.

o This system is highly adaptive, protecting individuals from repeated exposure to

harmful substances.

Abnormalities of Feeding
An eating disorder is an illness that causes serious disturbances to your everyday diet, such as eating
extremely small amounts of food or severely overeating. A person with an eating disorder may have
started out just eating smaller or larger amounts of food, but at some point, the urge to eat less or
more spiralled out of control. Severe distress or concern about body weight or shape may also signal
an eating disorder. Common eating disorders include anorexia nervosa, bulimia nervosa, and binge-
eating disorder.

Anorexia Nervosa

Anorexia nervosa is an eating disorder that occurs when a person refuses to eat an adequate
amount of food or is unable to maintain a minimally healthy weight for their height—a body mass
index below 18.5. Individuals with anorexia often have a distorted body image. Those with anorexia
view themselves as fat or bulky in certain areas and have an intense fear of gaining weight or
becoming fat.

Many people with anorexia nervosa see themselves as overweight, even when they are clearly
underweight. Eating, food, and weight control become obsessions. What they consume, how much,
and under what conditions becomes a preoccupation and is often obsessive in nature. People with
anorexia nervosa typically weigh themselves repeatedly, portion food carefully, and eat very small
quantities of only certain foods. Some people with anorexia nervosa may also engage in binge-eating
 followed by extreme dieting, excessive exercise, self-induced vomiting, and/or misuse of laxatives,
diuretics, or enemas.

Some who have anorexia nervosa recover with treatment after only one episode. Others get well but
have relapses. Still others have a more chronic, or long-lasting, form of anorexia nervosa, in which
their health declines as they battle the illness.

Anorexia nervosa displays the following symptoms:

The DSM-5 classifies symptoms of anorexia nervosa as follows:

• Refusal to maintain body weight at or above a minimally normal weight for one's age and height

• Intense fear of gaining weight or becoming fat, even though one is underweight

• Disturbance in the way in which one's body weight or shape is experienced

• Undue influence of body weight or shape on self-evaluation

• Denial of the seriousness of low body weight.

There are two main types of anorexia nervosa:

Restricting Type Anorexia Nervosa occurs when the primary method of weight loss involves dieting,
fasting, and excessive exercising—and not engaging in any bingeing or purging behaviors for at least
a three-month period.

Binge Eating/Purging Type Anorexia Nervosa occurs when the individual has engaged in episodes of
bingeing or purging behavior, such as self-induced vomiting, misuse of laxatives, diuretics, or
enemas.

Cause

Anorexia nervosa and other eating disorders are commonly found in cultures and settings where
thinness is seen as highly desirable. This is particularly the case in post-industrialized, high-income
countries where fashion trends, sales campaigns, and media often present thinness as a desirable or
typical trait. Some activities and professions, such as modeling and athletics, may promote a goal of
unusual leanness (more than is required for health) in order to do well.

The onset of an eating disorder can also be associated with a stressful life event. For young adults,
leaving home for college can be such an event. For older adults, other life transitions—returning to
work after raising a family, finding a new job, separation or divorce—can precipitate symptoms of an
eating disorder.

Temperamental factors, such as perfectionism and obsessional traits in childhood, are also
associated with eating disorders.

If left untreated, anorexia may lead to osteoporosis, cardiac problems, infertility, depression,
relationship difficulties, suicide, and even death from medical complications. Anorexia carries the
highest death rate of any psychiatric condition.
 Obesity
Obesity is characterized by excess body fat. Studies have shown that being obese is associated with
an increased risk of death from causes such as hypertension, stroke, heart disease, and other
conditions.

Obesity is typically measured by body mass index, or BMI, a value calculated as weight in kilograms
divided by height in meters squared. According to the Centers for Disease Control:

• A BMI of 25 to 30 is within the overweight range

• A BMI is 30 or higher is within the obesity range

• BMI of 40 or higher is considered severe obesity

Causes

An individual’s weight is the result of many overlapping factors, including environment, family
history and genetics, metabolism, and behavior. Genes strongly influence a person's weight, which is
why vulnerability to weight gain and obesity tends to run in families. But other factors in weight
gain, such as exercise habits and dietary choices, are more likely to be under an individual’s control.

People who are physically inactive are more likely to gain weight. One reason for such inactive
lifestyles is an increasingly sedentary culture taking hold in many highly developed countries. Many
jobs or at-home activities no longer require intense physical demands; whether working or engaging
in leisure, many children and adults spend much of their time in front of TVs, computers, or on their
phones. Those living in developed nations also typically rely on cars for transportation instead of
walking or biking. Other environmental challenges may include a lack of time for physical activity or
lack of access to recreational space or healthy foods. Research has also found an association
between obesity and insufficient sleep.

Research has shown that being overweight is significantly associated with an increased risk of death
from hypertension, dyslipidaemia (high cholesterol), type 2 diabetes, stroke, osteoarthritis, coronary
heart disease, gallbladder disease, sleep apnea and respiratory problems, and endometrial, breast,
prostate, and colon cancers.

Excessive food craving:

Cravings are hedonic responses to food, characterised by their intensity and their specificity. Food
cravings are extremely common, reported by the majority of young adults.

Overeating behaviour is supposedly a major contributing factor to weight gain and obesity. Binge
eating disorder (BED) with reoccurring episodes of excessive overeating is strongly associated with
obesity. Learning models of overeating behaviour and BED assume that mere confrontation with
food leads to a conditioned response that is experienced as food craving. Accordingly, individuals
with obesity and BED were shown to have high trait food cravings. To date, little is known about
differences in state food cravings and cue reactivity at the sight of palatable food in individuals with
obesity and BED compared to individuals with obesity without BED.