Control of Food Intake Flashcards
1
Q
[N] Why should we study food intake?
A
- 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]).
2
Q
Where is the fundic area in the stomach and what is that part of the stomach capable of doing?
A
3
Q
What are the control factors required for accomodation?
A
Vasoactive intestinal polypeptide (VIP) and nitric oxide (NO).
4
Q
What factors cause satiety?
A
PYY (peptide YY secreated in the pancreas) is a satiety factor that decreases gut mortality.
5
Q
What factor causes hunger?
A
Ghrelin.
6
Q
What controls the contractile movement around the pyloric antrum?
A
It is controlled by acetylcholine.
7
Q
[N] Describe some factors (such as FFA, CCK, ghrelin, PYY, etc.) that are important in the control of gut accommodation and motility/emptying.
A
- 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.
8
Q
How is food accommodated in the gastric reservoir?
A
- 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.
9
Q
[N] Describe what is involved in the relaxation of the stomach.
A
- 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.
10
Q
[N] Describe the actions of PACAP (pituitary adenylate cyclase -activating peptide).
A
- 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).
11
Q
What is vagotomy?
A
- 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).
12
Q
[N] How can gastric surgery impair accommodation and emptying?
A
- 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).
13
Q
Define hunger.
A
- 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.
14
Q
Define appetite.
A
- Appetite is the desire / drive to satisfy the body’s needs for food.
- It is a hunger-stimulated response.
15
Q
Define satiety.
A
Satiety is the state of being full after eating food (joyous moments - no longer need to continue eating).
16
Q
Define aphagia.
A
Aphagia is the inability or refusal to swallow.
17
Q
Define hyperphagia / polyphagia.
A
Hyperphagia / polyphagia is an abnormal desire for food (extreme unsatisfied drive to eat).
18
Q
Give a summary of the factors that influence food intake.
A
-
External factors -
- Food availability.
- Variety of food available.
- Social eating.
- Daily routine.
-
Emotional state -
- Stress.
- Anxiety.
- Depression.
- Physiological regulation
19
Q
What main input from the brain controls food intake?
A
- 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.
20
Q
Besides the hypothalamus, what other inputs control our feeding behaviour?
A
- Orexigenic and Anorexigenic neurotransmitters have been found in the hypothalamus.
- Orexigenic neurotransmitters increase our appetite, while anorexigenic neurotransimtter decrease our appetite.
21
Q
Describe the role of the prefrontal cortex in the executive control of food intake.
A
- The prefrontal cortex in important in food seeking behaviour.
- It is involved in the integration of sensory information from inside and outside the body.
- It also recieves emotional and cognitive information from the limbic system.
- The prefronta cortex helps one make choices by translating all of the homeostatic and environmental information into adaptive behavioural response.
22
Q
Describe the role of the limbic system in the executive control of food intake.
A
- The limbic system 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.
- The satiation of feeding behaviour is associated with motor planning and execution which are controlled by the cortico-limbic mechanisms that are under executive control.
23
Q
Feeding behaviour/food intake is modulated by many hypothalamic sites. List some of them.
A
- Lateral Hypothalamus (LH) = hunger / thirst centre.
-
Ventromedial Nucleus (VMN) = satiety centre.
- The VMN and LH have the ability to restrain feeding if required; a lesion of VMN would increase appetite, with weight gain that tends to persist.
-
Dorsomedial Nucleus (DMN) = modulates energy intake (hunger centre).
- Releasing NPY (neuropeptide Y) into the DMN increases feeding.
-
Paraventricular Nucleus (PVN) = modulates feeding behaviour.
- Controls feeding behaviour.
- If NPY, opioids, GABA (gamma-aminobutyric acid), etc. given, it leads to increased feeding.
- If leptin was given, it leads to decreased feeding.
- However GABA can also reduce feeding in certain contexts.
-
Arcuate Nucleus (ARC).
- They are sensitive to orexigenic factors.
- It contains neurons that produce orexigenic signals (NPY, opioids, dynorphin, β-endorphins, POMC (Pro-opiomelanocortin), galanin, amino acids, GABA and glutamate).
Lesion meaning - It is a region in an organ or tissue which has suffered damage through injury or disease, such as a wound, ulcer, abscess, or tumour.
Orexigenic signals meaning - It is an orexigenic, or appetite stimulant, is a drug, hormone, or compound that increases appetite and may induce hyperphagia (excessive eating).
24
Q
What is the role of the suprachiasmatic nucleus (SCN)?
A
- 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.
25
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).
26
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.
27
Describe some diurnal variation in food intake.
* Carbohydrates are metabolised during the day.
* Fats are metabolised at night.
* The hypothalamus responds to the switch between carbohydrate and fat metabolism.
28
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.
29
List some factors that can affect if food is sought or not?
* **Food preferences.**
* **Emotions.**
* **Environment.**
* **Life style.**
* **Circadian rhythm** - limits food intake to certain times (in some people).
30
How does glucose control food intake?
* The glucose concentration in the blood stimulates **gluco-receptors** in the **hypothalamus**.
* When there is **low blood glucose** concentration there is an **upregulation** of **hunger**.
* When there is **high** **blood glucose** concentration there is an **upregulation** of **satiety**.
31
Why do diabetic patients feel hungry despite having an increased blood glucose concentration?
* It is possible that the insulin doesnt have any effect as the patient is insulin resistant.
* It is also possible that the insulin receptor is not functional so the patient is unable to take up the glucose.
* It is possible in type 1 diabeties that the patient doesnt even release insulin.
32
Cold environments stimulate ______ while hot environments ______ appetite.
1. Feeding
2. Inhibit
33
How does afferent input affect food intake?
* Distension of a full stomach inhibits appetite.
* Contraction of an empty stomach stimulates appetite.
* Denervation of intestines and stomach seems to have no effect on food intake. E.g. vagotomy has no effect on food intake.
_Vagotomy meaning_ - It is a surgical operation in which one or more branches of the vagus nerve are cut, typically to reduce the rate of gastric secretion.
34
How does the deposition of fat control food intake?
* The more fat you have (in particular the white fat) the amount of leptin which is released from fat cells located in adipose tissues increases and this determines food intake.
35
How do gut hormones control food intake?
* Fat ingestion causes CCK (Cholecystokinin) release and the slowing of gastric emptying (sense of fullness).
* CCK (released from the I cells in the intestines or the nerve endings) and some statins such as somatostatin inhibit further food intake (they are satiety factors).
_Statins meaning_ - Statins are a group of medicines that can help lower the level of low-density lipoprotein (LDL) cholesterol in the blood. LDL cholesterol is often referred to as "bad cholesterol", andstatins reduce the production of it inside the liver.
36
What happens when you inject CCK into the brain?
* It causes the reduction of appetite and the size of helping is also reduced.
37
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.
* 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.
38
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.
39
What is leptin's role in the control of food intake?
* 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 (the white adipose tissue is an endocrine organ. Brown adipose tissue is important for keeping us warm, particularly in babies).
* It controls fat stores by operating a feedback mechanism between adipose tissue and brain where a larger amount of adipose tissue size will cause an increase in leptin secretion.
* It does this by increasing the expression of anorexigenic factors such [pro-opiomelanocortin (POMC), cocaine-and amphetamine-regulated transcript (CART), corticotrophin-releasing hormone (CRH), neurotensin]. This stimulates metabolic rate.
* It inhibits neuropeptide Y, which stimulates feeding.
40
Can a person be resistant to the effects of leptin?
* **Yes**.
* This can lead to binge eating, despite adequate or growing adipose tissue (obese).
* Hyperphagia and severe obesity occurs in in humans with leptin deficiency or leptin receptor defects.
* There is a high correlation of leptin levels with body fat in humans and animals.
41
What is the role of ghrelin in the control of food intake?
* Gherlin is an apetite inducing hormone (an orexin) that stimulates hunger.
* It is fast acting and stimulates food intake.
* It is released by the upper section of the stomach by cells called P/D1 cells, and also in the pancreas and adreanals in response to nutritional status.
* The circulating levels of ghrelin increase preprandially and decrease after a meal.
* It increases levels of orexigenic factors such as NPY (Neuropeptide Y), and AgRP (Agouti-related peptide) which generate hunger signals and you eat more.
* It suppresses the ability of leptin to stimulate anorexigenic factors (as they act reciprocally).
42
What is the role of obestatin in the control of food intake?
* 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 there is a 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.
