Physiology of feeding and satiety Flashcards
Which factors influence obesity?
- Genetics
- Environment
What diseases does obesity contribute to?
type 2 diabetes
hypertension
MI
cancer (colon)
osteoarthritis
Why do we need fat?
energy storage
prevention of starvation
energy buffer during prolonged illness
Why is it so difficult to lose fat?
re-programmes the brain
brain views it as normal
dieting is viewed as a threat to the body and defends new weight
How does the CNS influence energy balance and body weight?
- behaviour
- ANS activity
- Neuroendocrine system
What is the site of integration?
Brain
What is the neural centre responsible for the CNS influence over body fat?
Hypothalamus
What does lesioning of the ventromedial hypothalamus cause?
Obesity
What does lesioning of the lateral hypothalamus cause?
Leanness
What are the three factors of the control system for satiation?
- satiety signalling
- adiposity negative feedback signalling
- food reward
Define satiation?
Sensation of fullness generated during a meal
Define satiety?
period of time between termination of one meal and the initiation of the next
Define adiposity?
The state of being obese
Where is CCK secreted from?
enteroendocrine cells in duodenum and jejunum.
What determines the proportion of CCK released?
lipids and proteins in meal
How does CCK work?
Signals via sensory nerves to hindbrain and stimulates hindbrain directly (nucleus of solitary tract (NTS)).
What is glucagon-like peptide 1 a product of?
of pro-glucagon gene
Where is glucagon-like peptide 1 released from?
L cells
What stimulated glucagon-like peptide 1 release?
food ingestion
What does glucagon-like peptide 1 do?
Inhibits gastric emptying and reduces food intake (Hypo, NTS)
What is Oxyntomodulin a result of?
pro-glucagon gene
Where is Oxyntomodulin released from?
oxyntic cells of small intestine
When is Oxyntomodulin released in response to?
after meal
What does Oxyntomodulin do?
Suppress apetite
Where is peptide YY secreted from?
Endocrine mucosal L-cells of the GI tract
When do peptide YY levels increase?
Post-prandially
What does peptide YY do?
Inhibits gastric motility, slows emptying and reduces food intake (Hypo)
What is obestatin produced as a result of?
Gene that encodes ghrelin
Where is obestatin released from?
cells lining stomach/small intestine
What does obestatin do?
reduce food intake - may act to antagonise the actions of ghrelin - actions unclear at present.
What is ghrelin?
Octanoylated peptide
Where is ghrelin produced and released from?
produced and secreted by oxyntic cells in stomach
When do ghrelin levels increase?
before meals and decrease after meals
What raises ghrelin levels?
Fasting and hypoglycaemia
What does peripheral ghrelin do?
stimulates food intake (Hypo) and decreases fat utilization
What is the role of ghrelin containing neurones in the hypothalamus?
help control fat metabolism, increase lipogenesis (liver and adipose)
Which two hormones- produced in peripheral tissues can act on hypothalamic neurones?
Leptin
Insulin
Where is leptin made and released from?
Fat cells
Where is insulin made and released from?
pancreatic cells
What do insulin and leptin do?
inform the brain to alter energy balance, eat less and increase energy burn- this malfunctions in obesity
What does reduced leptin mimic?
Starvation, causing unrestrained appetite
Describe the structure of leptin?
member of the cytokine family, 146 aa long, made & secreted from adipocytes
Where is leptin found?
circulates in proportion to body adiposity
Where are there high levels of leptin and insulin receptors?
In the hypothalamus
What does intracerebroventricular leptin inhibit and cause?
inhibits food intake and decreases body weight
List the biological roles of leptin?
> Food intake/energy expenditure/fat deposition
Peripheral glucose homeostasis/insulin sensitivity
Maintenance of immune system
Maintenance of reproductive system
Angiogenesis
Tumourigenesis
Bone formation
What does insulin circulate in proportion to?
Adiposity
What does high intracerebroventricular (icv) insulin do?
inhibits food intake and decreases body weight of rodents
What are the hedonistic aspects of food linked to?
Sugar and fat
What areas are implicated in the hedonistic aspects of food?
> Ventral tegmental area
Nucleus accumbens
Striatum
Substantia nigra
What is the vast majority of human obesity characterised by?
High leptin levels
What does diet induced obesity result in?
Leptin resistance
- defective transport to brain
- altered signal transduction following leptin binding to its receptor
Which appetite suppressant drug is approved in USA?
Phentermine
Which drug is supposed to be marketed in feb 2018?
Mysimba
What is liraglutide mechanism?
unclear - has to be injected
Some concerns remain regarding thyroid and pancreatic cancer
What does bariatric surgery induce?
high level of complete resolution of Type 2 Diabetes (reverses insulin resistance in most cases)
What is the mechanism of bariatric surgery success?
unclear at present - but involve altered secretion of peptides from stomach and gut that affect beta cells and hypothalamus: e.g. GLP-1, PYY3-36, ghrelin
Do adults possess BAT?
yes
Neck, clavicle and spinal chord
What does BAT do?
Disperse energy as hear
What do thermogenic adipocytes do?
Increase energy expenditure uncoupling of oxidative metabolism from ATP production
What is the key function of UCP1?
“short circuits” proton gradient in mitochondria - accelerates fuel oxidation - produce heat
