Leptin and Obesity Flashcards
Risk factors of obesity?
Type 2 diabetes, heart attack, stoke, breast and colon cancer.
What is obesity?
The net result of over consumption of food, increased energy efficiency, and decreased physical activity.
Why is obesity an issue in fast developing countries?
Before they were developed - their genes made them efficient at converting food to body mass as this was vital for survival. But now that they have more food - this is just causing obesity.
Examples of energy intake?
Protein, fat, CHO
Examples of energy expenditure?
Physical activity, diet induced thermogenesis, BMR.
What signals does the hypothalamus process to control eating behaviour (feeding and energy expenditure)?
Internal signals…metabolic (glucose, lipids, aa), hormonal (leptin, insulin, glucagon), neural (gastric distension).
Psychological factors - food palatability and adverse food behaviours.
What is the main source of information on energy reserves in adipose tissue?
Leptin. Travels from adipose to brain via blood (hormone).
Explain how leptin works?
The amount of leptin produced is proportional to the amount of adipose tissue a person has. Binding of leptin to the leptin receptor INHIBITS feeding.
Explain the ob/ob mouse.
Ob gene encodes the leptin protein.
A homozygous mutant ob/ob would produce truncated inactive proteins and therefore wouldn’t be able to inhibit feeding - would be obese!
Explain the diabetes db/db mouse.
db gene encodes leptin receptor.
db/db = defective receptor protein.
db/db produces leptin but signalling can’t occur therefore obesity.
What happens if you do a parabosis experiment on ob/ob and db/db mice?
Link up the circulation.
Ob/ob mouse would now have leptin to respond to…therefore would decrease in body weight.
Db/db mouse still wouldn’t be able to respond to leptin….still be obese.
How constant does your body weight remain?
only increases about 10kg between 25 and 75.
Lipostatic/Adipostatic theory?
All about maintaining a constant lipid/adipose level.
The total body weight is maintained by regulating body fat content.
Hypothalamus senses the concentration os circulating factor which indicated the size of the fat stores.
What is the set point hypothesis?
A blood borne factor (leptin) controls body weight at a ‘set point’ (that individual level of fat reserves that are required to maintain normal life activities for that individual).
Leptin controls food intake and energy expenditure.
The signal is proportional to the size of the fat stores (and integrates with other regulators of food intake) to keep energy reserves constant.
Explain what happens if you increase adipose?
Increase leptin, increase beta oxidation, decrease intake.
What happens if you decrease adipose?
Decrease leptin, decrease beta oxidation, increase intake.
What is leptin designed to protect against?
Starvation.
Explain the leptin signalling pathway in the hypothalamus.
1) The leptin receptor exists as 2 monomers in the membrane.
2) When leptin binds…2 monomers come together and receptor forms around leptin.
3) Accessory proteins (JAK - Janus Kinase) attaches to phosphorylated tyrosine residues in the leptin receptor.
4) Jack causes phosphorylation of other tyrosine residues on the leptin receptor.
5) STAT (signal transducer and activator of transcription) binds the the phosphorylated tyrosine residues on the leptin receptor (x2)
6) STAT receptor dimerises and detaches from the leptin receptor.
7) STAT dimer is the functional transcription facotr which moves to the nuclus when it binds to promoter regions of certain genes (eg POMC)
Explain obesity and leptin resistance.
Expansion of adipose tissue…increase leptin secretion…increase plasma leptin concentration…continuous stimulation os the leptin receptor leads to a down regulation of leptin receptor signalling.
