APPETITE Flashcards
What are the 3 stimulants that control thirst and which one has the greatest effect?
Body fluid osmolality - strongest
Blood volume
Blood pressure
What is the function of ADH?
Acts on kidneys to regulate volume and osmolality of urine. More ADH = less urine and vice versa
How does the body sense blood osmolality and how does it correct changes?
Osmoreceptors:
Cell shrinks when plasma more concentrated
Cation channel proportion increase and cation influx
Membrane depolarisation
Signal sent to neurons of hypopituitary to increase ADH
Fluid retention and drinking
Vice versa
Where are osmoreceptors found?
Hypothalamic regions:
- Organum vasculosum of lamina terminalis (OVLT)
- Subfornical organs (SFO)
How does temporary relief of thirst come about and why?
Receptors in mouth, pharynx and oesophagus sense fluid before it has even been absorbed by the GI tract and causes temporary relief in order to prevent fluid overload
How does complete satisfaction of thirst come about?
Only once plasma osmolality is decreased or blood volume/pressure is corrected
How does the body correct low blood pressure/volume?
Low BP/BV senses by juxtaglomerular cells of renal afferent arteriole via stretch receptors. Renin is produced which converts angiotensinogen (liver) into angiotensin I. ACE (respiratory organs) then converts angiotensin I to II.
Angiotensin II increases thirst, aldosterone, ADH, vasoconstriction via sympathetic activity
Describe the laws of body weight homeostasis
Reduction in fat mass: Decreased SNS activity Increased food intake Decreased energy expenditure Decreased thyroid activity
Adipose tissue expansion:
Increased SNS activity
Decreased food intake
Increased energy expenditure
What signals regulate appetite and where?
Ghrelin, PPY and other gut hormones
Neural input from periphery/brain regions
Leptin
Signals to hypothalamus which provides a link between higher brain circuits and stimulus.
What is the definition of orexigenic and anorectic?
Orexigenic - appetite stimulant
Anorectic - appetite suppressive
List the regions of the hypothalamus involved in appetite regulation and their roles
Paraventricular nucleus - a terminal of NPY/Agrp/POMC neurones, also has neurones which project to hypopituitary
Ventromedial hypo - satiety, lesions here lead to severe obesity
Arcuate nucleus - POMC neurones decrease food intake when activated
Lateral hypo - produces orexigenic peptides
Which region of the hypothalamus is the most important for energy balance?
Arcuate nucleus
How is the arcuate nucleus able to integrate peripheral and central feeding signs?
Incomplete blood brain barrier allowing access to peripheral hormones
What are the two populations of neurones present in the arcuate nucleus?
NPY/Agrp neurones (stimulates feeding) POMC neurones (inhibits feeding)
How do the NPY/Agrp neurones work?
Makes orexigenic peptides NPY and Agrp
Agrp is a melanocortin receptor antagonist
Both peptides come from the same neurone
What are the effects of leptin on the arcuate nucleus?
Leptin stimulates POMC neurones and inhibits NPY/Agrp neurones
What is the role of the melanocortin system?
Central regulator of energy balance in both feeding behaviour and energy expenditure
It is a collection of central nervous circuits
Describe/draw the melanocortin system
Agrp and POMC neurones from arcuate nucleus produce Agrp and alpha-MSH (melanocortin) respectively.
These bind to MC4R (melanocortin 4 receptor) on a second order neurone in the paraventricular nucleus
Agrp is a MC4R antagonist
Alpha-MSH is a MC4R agonist
Activation of MC4R causes decreased food intake
What are melanocortins?
Products of POMC cleavage
What human CNS mutations cause a change in appetite?
POMC def and MC4R mutations cause morbid obesity
No NPY/Agrp mutations associated with appetite
List the other brain regions that signal to the hypothalamus
Higher centres
Amygdala
Other parts of hypothalamus e.g. lateral hypo
Vagus nerve to brainstem to hypothalamus
What is the role of the adipostat mechanism?
The bodies control and sensitivity to adiposity and thus weight. Signal to control appetite and energy expenditure
How does the adipostat mechanism work?
Leptin produced by adipocytes in white adipose tissue. Hypothalamus senses the concentration of the hormone and alters neuropeptides to increase/decrease food intake
Where does leptin act?
Arcuate and ventromedial nuclei to regulate appetite and thermogenesis (energy expenditure) in adipostat mechanism
Other than the adipostat mechanism what other roles does leptin have?
Development of atherosclerosis via innate immune system
Low levels in Alzheimer’s disease and depression
What is congenital leptin deficiency?
Lack of leptin causing severe obesity in early life as children are constantly hungry and eating
Exogenous leptin effective in reducing weight
Rare
What is the relationship between leptin and obesity?
Serum leptin concentrations correlated to percentage body fat suggesting obese individuals become insensitive to endogenous leptin production
Exogenous leptin ineffective as weight control drug
What 3 ways can go wrong in leptin’s mechanism of action?
Absent leptin e.g. congenital leptin def
Leptin resistance e.g. in obese people
Mutation in leptin/receptor
When body fat is high, what is leptin?
High and vice versa
Proportional to fat mass
What causes us to feel less hungry after a meal?
Bulk in stomach
Nutrients in circulation
BUT MOST IMPORTANTLY
Hormones from gut
What cells secrete GI hormones?
Enteroendocrine cells of stomach, pancreas and small intestine
Which two GI hormones regulate appetite?
Ghrelin - increase appetite
Peptide YY - reduces appetite
How does ghrelin work?
Highest levels before meals to help prepare food intake by increasing gastric motility and acid secretion.
Stimulates NPY/Agrp neurones
Inhibits POMC neurones
Increases appetite
Regulates reward, taste sensation, memory and circadian rhythm
How does PYY work and where is it secreted?
Short peptide secreted in terminal ileum and colon in response to food arriving to TI and colon
Inhibits NPY neurones
Stimulated POMC neurones
Decreases appetite - can be injected as a drug
What comorbidities is obesity associated with?
Depression Stroke MI Hypertension Diabetes - PVD Gout Osteoarthritis Bowel cancer and others Sleep apnoea
