Control of Food Intake

Question 1

Why should we study food intake?

Answer 1

• it’s a physiological process common to all animals
• to combat obesity and its consequences
• to combat endocrine disorders
• to understand its clinical significance in several settings (eg. severe wasting due to chronic illness)

Question 2

Describe some factors (such as FFA, CCK, ghrelin, PYY, etc.) that are important in the control of gut accommodation and motility/emptying.

Answer 2

• ghrelin is secreted by the stomach fundus and increases the sense of hunger and stimulates gastric emptying
• PYY signals satiety and inhibits gut motility
• ghrelin stimulates neuropeptide Y and AgRP neurons, while PYY has been shown to exert inhibition of the same neurons in animals
• obestatin, a peptide derived from the same prehormone as ghrelin, opposes the effects of ghrelin
• amylin helps reduce food intake through the medulla of the brainstem and by delaying gastric emptying
• enterogastrones (secretin, CCK (cholecystokinin), GIP(gastric inhibitory peptide)) are hormones secreted by the ‘mucosa of the duodenum’ in the lower GI tract in response to dietary lipids that inhibit the aboral motion of chyme

Question 3

Describe what is involved in the relaxation of the stomach.

Answer 3

Relaxation of the reservoir (fundus) is mediated by reflexes and can be differentiated into 3 types: receptive (mechanical stimulation of the pharynx - mechanoreceptors, sight), adaptive (vagal innervation (NO/VIP), the tension of the stomach), and feedback (nutrients, CCK).

There are many other mediators important in the relaxation of the stomach.

Briefly, the receptive, adaptive and feedback-relaxation of the stomach are mediated by non-adrenergic, non-cholinergic (NANC) mechanisms (ie., inhibition involving NO, VIP, etc.) as well as by reflex chains involving the release of noradrenaline. There is some evidence that when the stomach is ready to receive the food, very early on, noradrenaline is released from the sympathetic nerve fibres which help the stomach to relax, probably via constriction of blood flow.

Question 4

Describe the actions of PACAP (pituitary adenylate cyclase-activating peptide).

Answer 4

It is isolated from the pituitary and has been shown to stimulate adenylate cyclase activity in the anterior pituitary.

There are high levels in the brain, but it is also found in the gut (the myenteric and submucosal ganglia). It mediates the neuronal regulation of gastric acid secretion (thus mediating intestinal motility). It also stimulates the relaxation of colonic smooth muscle and stimulates pancreatic secretions (it stimulates insulin and glucagon secretion in humans).

Question 5

How can gastric surgery impair accommodation and emptying?

Answer 5

Prior gastric surgery may result in gastroparesis (delayed gastric emptying). Around 5% of patients who undergo a vagotomy as part of their surgical correction for peptic ulcer disease or malignancy develop symptoms of early satiety (as well as nausea, and bloating from gastric stasis), in the absence of a mechanical obstruction.

This has also been observed after highly selective vagotomies. Disturbance of fundic and antral contractility have been documented on several occasions. Non-motor factors may be involved, as symptoms do not always correlate with delays in gastric emptying.

In summary, a vagotomy impairs accommodation and gastric compliance.

Question 6

Define hunger, appetite and satiety.

Answer 6

HUNGER: it is the discomfort caused by the lack of food and the desire to eat - a strong craving/ drive for food/ sensation of emptiness in the stomach

APPETITE: the desire/ desire to satisfy the body’s needs for food - a hunger-stimulated response

SATIETY: the state of being full after eating food (joyous moments - no longer need to continue eating)

Question 7

Define aphagia and hyperphagia/polyphagia.

Answer 7

APHAGIA: the inability or refusal to swallow

HYPERPHAGIA/POLYPHAGIA: an abnormal desire for food (extreme unsatisfied drive to eat)

Question 8

Give a summary of the factors that influence food intake.

Answer 8

• external factors - eg. food availability, variety of food available, social eating, daily routine
• emotional state - stress, anxiety, depression
• physiological regulation

Question 9

What main input from the brain controls food intake?

Answer 9

The hypothalamus is the control centre for appetite and food intake. It controls our hunger and thirst.

The base of the hypothalamus has several nuclei that regulate energy homeostasis. It controls the appetite, the sixe of the helping, and our ingestive behaviour.

Question 10

Besides the hypothalamus, what other inputs control our feeding behaviour?

Answer 10

Orexigenic and Anorexigenic neurotransmitters have been found in the hypothalamus.

Orexigenic neurotransmitters increase our appetite, while anorexigenic neurotransimtter decrease our appetite.

Question 11

Feeding behaviour/food intake is modulated by many hypothalamic sites.

List some of them.

Answer 11

1) Lateral Hypothalamus (LH) = hunger centre

2) Ventromedial Nucleus (VMN) = satiety centre
[the VMN and LH have the ability to restrain feeding id required; a lesion would increase appetite, with weight gain that tends to persist]

3) Dorsomedial Nucleus (DMN) = modulates energy intake (hunger centre)
[releasing NOY into the DMN increases feeding]

4) Paraventricular Nucleus (PVN) = modulates feeding behaviour
[controls feeding behaviour; if NPY, opioids, GABA, etc. given, leads to increased feeding, while if leptin was given, it leads to decreased feeding]

5) Arcuate Nucleus (ARC) = neurons produce orexigenic signals (NPY, opioids, dynorphin, β-endorphins, POMC, galanin, amino acids, GABA and glutamate)

Question 12

What is the role of the suprachiasmatic nucleus (SCN)?

Answer 12

It is responsible for controlling circadian rhythms. It is situated in the hypothalamus; it’s tiny in size and sits directly above the optic chiasm.

Question 13

Describe the regulation of appetite in the hypothalamus by the 5-HT2C agonist.

Answer 13

Appetite is regulated by the balance between an appetite-stimulating pathway that releases agouti-related peptide (AgRP) and neuropeptide Y (NPY), and an appetite suppressing pathway that releases α-melanocyte stimulating hormone (α-MSH).
The appetite suppressing neurons make the precursor pro-opiomelanocortin (POMC), which is broken down into α-MSH, which in turn binds to melanocortin 4 receptors (MC4R) to suppress the appetite. When there is no occupancy of MC4R receptors by α-MSH, there is stimulation of the appetite.

A serotonin 5-HT2C agonist, such as meta-chlorphenylpiperazine (mCPP), hypothetically binds to 5-HT2C receptors on POMC neurons in the appetite suppressing pathway, activating POMC neurons and leading to the release of α-MSH, which binds to MC4R to suppress the appetite.

Question 14

Describe some diurnal variation in food intake.

Answer 14

• carbohydrates are metabolised during the day
• fats are metabolised at night
• the hypothalamus responds to the switch between carbohydrate and fat metabolism

Question 15

Describe the role of the prefrontal cortex and the limbic system in the executive control of food intake.

Answer 15

The prefrontal cortex receives sensory information from inside and outside the body, as well as emotional and cognitive information from the limbic system, and it is intimately connected to cortical areas involved in motor planning and execution. All the available homeostatic and environmental information is translated into adaptive behavioural responses - in brief, we make choices.

Question 16

What is the limbic system?

Answer 16

This is a complex system of nerves and networks in the brain. It involves area around the cortex concerned with instinct and mood.

It has control over the following emotions: fear, pleasure, anger; it also drives hunger, sex, dominance, care of offspring, etc.

Question 17

Between the sides of the hypothalamus, where is the switch?

Answer 17

Removal of the lateral hypothalamus causes hypophagia (decreased feeding), leading to death due to severe weight loss.
On the other hand, removal of the ventromedial hypothalamus causes hyperphagia (increased feeding).

Thus, feeding is regulated by a balance of stimulating and inhibiting forces in the hypothalamus.

Question 18

How does insulin decrease feeding behaviour?

Answer 18

Individuals with insulin-dependent diabetes mellitus (IDDM) are hyperphagic - such individuals are not obese because insulin is required for adipocytes to store fat, such that the excess calories consumed are wasted via excretion in the urine.

Glucagon’s metabolic functions are, in many respects, opposite to those of insulin. A prominent, physiological role for glucagon in to stimulate glucose production via hepatic glycogenolysis or gluconeogenesis, thereby helping maintain euglycaemia during stages of rapid glucose utilisation or fasts, respectively. It is also believed that glucagon is also secreted as food is ingested, and that provides a satiety signal leading to termination of the meal.

Question 19

In detail, describe the role of insulin in the control of food intake.

Answer 19

Insulin is secreted into the blood from the pancreas in direct proportion to the amount of fat stored in white adipose tissue. As it circulates through brain capillaries, a small amount of insulin is transported into the brain where it acts on insulin receptors on neurons with either net catabolic or anabolic activity (for example, in the arcuate nuvcleus of the hypothalamus). These neyrines in turn influence energy homeostasis (food intake and energy expenditure) and ultimately the amount of fat stored in the body by exerting a net catabolic action.

Question 20

What hormones affect lipolysis?

Answer 20

Insulin inhibits lipolysis in adipocytes.

Ghrelin, NA, adrenaline, GH, testosterone and cortisol induce lipolysis.

Question 21

How do insulin, glucagon and amylin participate in the regulation of energy homeostasis?

Answer 21

Insulin, glucagon and amylin are all secreted from the endocrine pancreas.

Insulin acts on both the liver and forebrain to reduce energy intake as well as to suppress hepatic glucose production. Glucagon acts mainly at the liver where it increases glucose production while generating a signal to reduce energy intake that is relayed to the hindbrain. Amylin acts directly at the hindbrain to reduce energy intake. It acts upon the NTS (nucleus of the solitary tract) and AP (area postrema) and induces their stimulation.

Question 22

What are the effects of somatostatin on control of food intake?

Answer 22

There is overwhelming evidence that somatostatin decreasea appetite. it does the same thing as CCK and appears to work via the vagus nerve, like CCK.

Question 23

What is leptin’s role in the control of food intake?

Answer 23

Leptin is a hormone that plays a central role in the regulation of food intake and energy expenditure. Leptin is secreted by white adipocytes and gastric cells.

Gastric leptin is involved in the short-term regulation of digestion, including the delay of gastric emptying, absorption of nutrients by the intestinal wall and secretion of gastric, intestinal and pancreatic hormones.

On the other hand, leptin secreted by white adipocytes acts primarily on the hypothalamus for the long-term regulation of food intake.

Therefore, the coordination of adipose and gastric leptins ensures the proper management of food processing and energy storage.

Question 24

How does low blood glucose affect ghrelin?

Answer 24

In the stomach, ghrelin is produced by cells called P/D1 cells in the upper section of the stomach.
Increased glucose levels inhibit its expression in the P/D1 cells. A drop in blood glucose levels below the threshold activates the expression of ghrelin. This reaches the arcuate nucleus of the hypothalamus (ARC) via the bloodstream and activated the expression of agouti-related peptide (AgRP) and NPY (and cannabinoids). Both AgRP and NPY generate hunger signals by stimulating the orexigenic neuron.

Question 25

What is the role of obestatin in the control of food intake?

Answer 25

It is produced in the epithelial cells of the stomach. It is encoded by the ghrelin gene, but it opposes the effects of ghrelin on food intake.

It suppresses food intake (suppresses appetite, so decreases body weight gain). It antagonises ghrelin-induced food intake (and growth hormone secretion).

The imbalance of ghrelin and obestatin may have a role in obesity, as a decreased ghrelin/ obestatin ratio has been found to charecterise obesity in women.

Question 26

Describe the proposed new formulation for appetite control.

Answer 26

A proposed tonic signal for the drive to eat that reflects the body’s demands for energy arises (mainly) from free fat mass (FFM) and resting metabolic rate (RMR). In turn, this drive is under tonic inhibition from leptin, whose actions reflect the number of stored energy reserves in the body. As the amount of adipose tissue increases, leptin insensitivity occurs and this tonic inhibition is reduced. The drive to eat is periodically interrupted and suppressed by episodic signals in the form of peptides that are released from the Gi tract in response to food consumption. The resulting pattern of eating is a consequence of the interactions between tonic and episodic physiological signals.

Prolonged exercise displays a dual-process action by stimulating hunger (an effect that is highly variable between individuals) but also by increasing post-prandial satiety signalling through an effect on GI peptides.