Control of Food Intake Flashcards
[N] Why should we study food intake?
- It’s a physiological process common to all animals.
- To combat obesity and its consequences.
- To combat endocrine disorders (e.g. hypothalamic sarcoid)
- To understand its clinical significance in several settings (eg. severe wasting due to chronic illness [disease called cancer cachexia]).
Where is the fundic area in the stomach and what is that part of the stomach capable of doing?
What are the control factors required for accomodation?
Vasoactive intestinal polypeptide (VIP) and nitric oxide (NO).
What factors cause satiety?
PYY (peptide YY secreated in the pancreas) is a satiety factor that decreases gut mortality.
What factor causes hunger?
Ghrelin.
What controls the contractile movement around the pyloric antrum?
It is controlled by acetylcholine.
[N] Describe some factors (such as FFA, CCK, ghrelin, PYY, etc.) that are important in the control of gut accommodation and motility/emptying.
- Ghrelin is secreted by the stomach fundus and increases the sense of hunger and stimulates gastric emptying.
- PYY (peptide YY secreated by pancreas) 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.
How is food accommodated in the gastric reservoir?
- The proximal third of the stomach (fundus plus oral corpus) relaxes during swallowing so that it can hold large amounts of food with limited increases in intraluminal pressure (presure within the lumen).
- This mechanism has been called “receptive relaxation” and is mediated by a vago-vagal reflex.
- When the food bolus reaches the stomach, gastric relaxation is maintained by another reflex starting from mechanoreceptors in the gastric wall.
- This second mechanism has been named “adaptive relaxation” or “gastric accommodation” and involves both intramural and vagal reflex pathways, whose inhibitory neurons are always intramural.
- The inhibitory neurons release the neurotransmitters, nitric oxide (NO), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase (AC)-activating peptide (PACAP) and/or ATP in order to relax the muscle.
- As the food begins to get digested the nutrients can also impact on the relaxation effect.
- A peptide hormone of the gastrointestinal system called Cholecystokinin (CCK) is secreated and is responsible for stimulating the digestion of fats and proteins (when CCK is released you know there must be lipids in the diet).
- This is the feedback relaxation.
[N] Describe what is involved in the relaxation of the stomach.
- 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).
- 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 (i.e. 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.
[N] Describe the actions of PACAP (pituitary adenylate cyclase -activating peptide).
- 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).
What is vagotomy?
- Vagotomy is a surgical operation in which one or more branches of the vagus nerve are cut, typically to reduce the rate of gastric secretion (e.g. in treating peptic ulcers).
- It reduces accommodation and gastric compliance (it doesnt have a significant impact as there are other factors that can control feeding and feeding behaviour).
[N] How can gastric surgery impair accommodation and emptying?
- 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.
Gastric compliance = accommodation and perception of distension (an enlargement, dilation, or ballooning effect).
Define hunger.
- Hunger is the discomfort caused by the lack of food and the desire to eat.
- It is a strong craving/drive for food/sensation of emptiness in the stomach.
Define appetite.
- Appetite is the desire / drive to satisfy the body’s needs for food.
- It is a hunger-stimulated response.
Define satiety.
Satiety is the state of being full after eating food (joyous moments - no longer need to continue eating).
Define aphagia.
Aphagia is the inability or refusal to swallow.
What main input from the brain controls food intake?
- 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.
- These nuclei control the appetite, the size of the helping, and our ingestive behaviour.
What is the role of the suprachiasmatic nucleus (SCN)?
- It is situated in the hypothalamus; it’s tiny in size and sits directly above the optic chiasm.
- It is responsible for controlling circadian rhythms (Appetite or the sensation of hunger will lead to the mood / drive to eat).
- Individual-based requirements (e.g. neural, metabolic and hormonal) may alter feeding behaviour.
Circadian rhythm meaning - Often referred to as the “human body clock,” the circadian rhythm is the 24-hour cycle that tells our bodies when to sleep, rise, and eat—regulating many physiological processes.
What is the role of the medial amygdaloid nucleus?
- The medial amygdaloid nucleus (MeA) is a sub-region of the amygdaloid complex that has been described as participating in regulating food intake.
- There are particular ligands that act on this site.
- Such as ligand 5-hydroxytryptamine / serotonin (5-HT) has been known to play an important role in regulating appetite and food intake via 5-HT2C and 5-HT1A (is a subtype of 5-HT).
Describe the regulation of appetite in the hypothalamus by the 5-HT2C agonist.
- 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.
Where is the switch that controls food intake? How does it regulate food consumption?
- The switch is situated in the hypothalamus.
- Removal of the lateral hypothalamus causes hypophagia (decreased feeding), leading to death due to severe weight loss. Stmulation of lateral hypothalamus can cause hyperphagia.
- On the other hand, removal of the ventromedial hypothalamus causes hyperphagia (increased feeding).
- But stimulating ventromedial (wall of paraventricular) nuclei leads to aphagia.
- Thus, feeding is regulated by a balance of stimulating and inhibiting forces in the hypothalamus.
Describe the role of insulin in the control of food intake.
- Insulin releases a factor called adiponectin that regulates how the body will respond to insulin.
- 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 nucleus of the hypothalamus).
- If there is a catabolic effect: -
- There will be a reduced food intake.
- This leads to the reduction of body fat.
- If there is an anabolic effect: -
- There will be an increase in food intake.
- This leads to an increase in body fat.
- If there is a catabolic effect: -
- These neurons 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.
Arcuate nucleus meaning - It is a collection of neurons (nerve cells) in the hypothalamus of the brain. Some arcuate neurons contain dopamine and act to inhibit the release of the hormone prolactin by the pituitary gland. Other arcuate neurons contain a substance called neuropeptide Y (NPY) and influence hunger.
How do insulin, glucagon and amylin (pancreatic hormones) participate in the regulation of energy homeostasis?
- 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.
- The effect of all 3 is to inhibit eating and reduce the meal size.
- Insulin, glucagon and amylin are anorexigenic agents.
