Neurochemical Control of Food Intake Flashcards
How is BMI calculated?
Weight in kg/(Height in m)^2
What does a BMI of 25 mean?
Normal
What does a BMI of 25 to 30 mean?
Overweight
What does a BMI of over 30 mean?
Obese
How does obesity occur?
When the calorie intake is greater than the calories burned
What are the three ways the body can deal with the excess dietary calories?
Convert excess fuel to fat and store it in adipose tissue
Burn excess fuel by extra exercise
Waste fuel by diverting it to heat production
Where does thermogenesis occur?
Uncoupled mitochondria
What does excess adiposity lead to?
Common chronic diseases like diabetes, fatty liver and heart failure
What is the primary physiological role of white adipose tissue?
- Function as a daily buffer of circulating lipids
Store dietary lipids in the fed states
What do white adipose tissues do in the fasted state?
Release free fatty acids in the fasted states
What do white adipose tissues do in the fed state?
Store dietary lids in the fed states
Based on studies and graphs what are the results of DCR and VLCD diets?
A percentage of starting body weight is lost during the first 12 months but then is gradually regained.
What is the lipostat theory?
Fat-borne factors act on the brain to regulate energy homeostasis and control levels of adiposity through different mechanisms
What mechanisms control the levels of adiposity?
Inhibiting eating behavior
Increasing energy consumption
When are the mechanisms of controlling adiposity levels initiated?
Whenever the body exceeds a specific value known as the setpoint
When are the mechanisms inhibited?
When the body weights drops below set point, patients starts eating and again and decreases energy consumption.
What happens to the body during diet that affects the set point?
When starting a diet, the fat reserve decreases, which causes the brain to think you are running out of energy and basically starving, no matter how overweight you may be. Thus the brain forces you to eat.
What is leptin?
A peptide hormone encoded by the ob gene.
Where is leptin mainly secreted?
Mainly secreted by the adipocytes
What is the function of leptin?
It carries the message about the level of fat reserves in the body
What is monogenic obesity?
Obesity resulting from a mutation or deficiency in a single gene (ob gene)
In mice; what happens when there are two defective copies of the ob gene?
Their serum cortisol levels are elevated
They grow abnormally
They exhibit unrestrained appetite
What is the result of having two defective copies of the ob gene (as seen in mice)?
They become severely obese
What is monogenic obesity like in humans?
They exhibit an unrestrained appetite
What is the treatment of monogenic obesity in humans?
Leptin injections
How do leptin injections work?
Increased energy expenditure and reduced eating, marked weight loss
What is the difference in genes between obese people and monogenically obese individuals?
Obese people do not have a defective ob gene, and they also have high levels of leptin.
Individuals suffering from monogenic obesity have defective ob gene and thus cannot produce leptin
What is leptin resistance?
Desensitization to leptin, when too much is given.
What is the mechanism of leptin?
It regulates adipose-tissue mass by promoting lipolysis and thermogenesis through a negative feedback, through the sympathetic nervous system.
What is the process of lipolysis?
Leptin is released from the adipose tissues, which are neural signals via sympathetic neurons.
The adipose cells circulating have receptors for nor-adrenaline which activates the release of adenocyclase when bound. There is phosphorylation of ATGL, HSL, and MGL.
Fat stored in adipocytes gets converted into fatty acids and glycerol and moves to the liver to be metabolized.
How is thermogenesis initiated?
By promoting uncoupling proteins activity
Where does leptin act in the brain?
Hypothalamic arcuate nucleus
Which are the appetite-stimulating neurons?
The orexigenic
How do orexigenic neurons work?
Stimulate eating by producing and releasing neuropeptide Y (NPY) which causes the next neuron in the circuit to send the signal to the brain to eat more.
Which are the appetite-suppressing neurons?
The anorexigenic
How do anorexigenic neurons work?
Anorexigenic neurons in the arcuate nucleus produce α-MSH. The release of α-MSH causes the next neuron to send the signal to the brain to eat less
What is α-MSH formed by?
Its precursor polypeptide precursor pro-opiomelanocortin (POMC)
What are orexigenic and anorexigenic neurons activated by?
Leptin, when leptin bind to their receptors, it gets phosphorylated and releases STAT3
What is STAT3?
It is a protein that regulates the signal sent to brain through the neurons to either increase or decrease appetite
What is insulin?
A hormone secreted from the β-cells in the pancreas
Where are insulin receptors expressed? How does that link to leptin?
In both NPY and POMC neurons, it also regulates caloric homeostasis as it acts on the same neurons and in the same way as leptin
What happens if the POMC neurons are activated?
Appetite is reduced
What is the function of leptin and insulin?
The regulation of long-term level of fat stored in the body.
Is obesity a genetic condition?
Rarely, obesity occurs in families according to CLEAR inheritance patterns caused by changes in a single gene
What is the most commonly implicated gene in familial obesity?
MC4R which encodes the melanocortin 4 receptor
What is the effect of mutations in the MC4R gene?
Diminishment of its function
How common are mutation in the MC4R gene in the obese population?
A small fraction, <5%
What is the main clinical sign of kids who suffer from the MC4R mutation?
Affected children feel extremely hungry and become obese because of hyperphagia
What are L cells?
Endocrine cells and not absorbing cells
What is the function of L cells?
To identify what kind of nutrient/substance has arrived in the intestine
Where are GLP1 and GLP1/PYY mainly found?
Duodenum/Jejunum
Rectum
Where is Gherkin primarily found?
In the stomach
Where is GIP mainly found?
Duodenum
What is Gherlin?
The hunger signal
A peptide hormone that is synthesized and released from endocrine cells of the stomach.
Does appetite change immediately if there is an imbalance in leptin?
No, however there are other hormones that have an immediate effect on appetite
What is the function of Gherlin?
Excites orexigenic neurons in the arcuate nucleus
Inhibits anorexigenic POMC nuerons
When is Gherlin released?
Before a meal, in order to stimulate hunger and tell the body to eat
What is the relation between Gherlin and insulin?
Negative correlation
How does the size/volume of the stomach relate to appetite?
Usually enlarged gastric capacity is related to overeating
What is the relation between glucose and L cells?
L cells detect the glucose through glucose transporters.
Glucose binds with sodium and the positive charge of the sodium causes changes in the membrane potential.
What is the result of membrane changes caused by the sodium?
Increase in calcium secretion which releases the gut hormones
What are the gut hormones?
GLP 1
GIP
CCK
SCT
What is the effect of glutamine on GLP1?
Triggers and potentiates GLP1 secretion by raising cytosolic Ca2+ and cAMP
How do different amino acids have different effects on the concentration of insulin released?
Different amino acids cause different levels of glucose secretion and thus insulin
How does insulin give a heads up about storage of glucose?
Insulin activates the β-cells in the pancreas and gives a heads-up to store glucose
What is the incretin effect?
The phenomenon where oral glucose elicits higher insulin secretory responses than does intravenous glucose
Where are GLP1 and PYY synthesized and secreted?
L cells in the large intestine
What are the functions of GLP1?
Stimulating insulin secretion and directly activating POMC neurons (anorexigenic)
How does GLP1 reduce food intake?
Through signaling mechanisms requiring functional GLP1 receptors in the arcuate nucleus
What is Semaglutide?
A glucagon-like peptide 1 analogue (GLP1 analogue)
What is Tirzepatide?
A novel GIP and GLP1 receptor agonist, combination of both, works even better than mono therapy
What are the two common types of bariatric surgeries?
Roux-en-Y gastric bypass
Vertical sleeve gastrectomy
Which kind of patients does bariatric surgery specifically benefit?
Type 2 diabetes patients
How does bariatric surgery help type 2 diabetes patients?
Reduced plasma glucose levels after bariatric surgery (due to loss of body weight and adiposity) improve insulin sensitivity
Bariatric patients have elevated post…?
Post-prandial insulin secretion
What happens during the RYGB procedure?
The esophagus is attached to the pylorus, completely bypassing the stomach.
Decreased absorption
What happens during the vertical sleeve gastrectomy?
Removal of about 80% of the stomach.
Adrenaline levels will be much less because the patient gets fuller faster and thus eats less.
How does bypass surgery help GLP1 secretion?
Increased nutrient flow to the distal gut
Increased postprandial GLP1 triggers higher insulin levels
