Body nutrient status: Informing brain about body energy stores (Prof Ashford) Flashcards
What are the two main methods of feedback between CNS and organs
Neural and endocrine
Describe satiety signals that control meal size
Upper GI tract signals via vagus nerve and sympathetic afferents converge on the nucleus of the solitary tract (NTS and hypothalamus)
Where does long term energy balance information mainly derive from?
The pancreas and adipose tissue
What are the three main factors that underlie regulation of food intake
1) Satiety signalling
2) Adiposity negative feedback signalling
3) Food reward
What is satiation?
The sensation of fullness generated during a meal
What is satiety?
Period of time between termination of one meal and the initiation of the next
What is adiposity?
The state of being obese
Describe ob/ob mice
Missing the circulating factor (the gene that encodes leptin). Causing it to become obese, hyperphagic, hyperinsulinaemic, hyperglycaemia and insulin resistant
Describe db/db mice
Lack functional receptor (gene encoding leptin receptor). Causing it to be obese, hyperphagic, hyperinsulinaemic and overtly diabetic
What does lack of leptin cause in relation to obesity and diabetes
Causes both (shit question I know I’m sorry)
What else is leptin required for?
Normal immune function, reproductive systems and regulation of blood pressure
Leptin on ovulation, puberty, angiogenesis and tumours
Thin women stop ovulating, it regulates onset of puberty, enhances angiogenesis and is produced locally in some tumours
What is the main leptin receptor
LEP-R
What are the splice variants of LEP-R known as
LEP-R a-f
Why is LEP-Rb most important?
It is the longest and has the intracellular motifs required for signalling
Where is leptin transported across the BBB
Median eminence
Where are LEP-Rb receptors particularly abundant?
Hypothalamus (ARC, LHA and VMH)
Where is leptin produced
White adipose tissue. Therefore plasma leptin and adipose tissue mass are highly correlated
What effect does fasting have on leptin levels
Decreases leptin
What is lipodystrophy
Rare disorder where individuals have few or no fat cells and store lipids elsewhere (muscle or liver) and have a high lipid level in blood. Basically fat redistribution
What disease patients are prone to lipodystrophy
HIV patients
What is the name of a synthetic injectable analogue of leptin
Myalept (metraleptin)
What is rabson mendenhall syndrome
Extreme insulin resistance
What two diseases can leptin therapy improve insulin resistance
Rabson mendenhall syndrome and HIV-1
What happens if you destory ARC and centrally inject leptin and what does this show
It no longer reduces food intake. This shoes LEP-Rb is localised strongly to ARC neurones (NPY and AgRP and POMC/CART)
Which hypothalamic mRNA does leptin increase/decrease
Increases: CART/POMC
Decreases: NPY/AgRP
What effect does leptin have on neurites in the ARC (and which age especially?)
Increases growth and especially in neonates
What other molecules similar to leptin is also an adiposity signal?
Insulin
How does insulin get into the rain
There is an insulin related transport system in brain microvessels
Just rememer insulin and leptin are so similar
GOT IT????
Is insulin anabolic or catabolic?
Anabolic (constructs molecules from smaller ones)
How is insulin delivered to the hypothalamus in humans
Intranasally
What does insulin when delivered to hypothalamus
Modulates hypothalamic neuronal activity, improves whole body insulin sensitivit, promotes lipogenesis and peripheral fat accumulation (white adipose) and finally increases adaptive thermogenesis (brown adipose
How does insulin reduce hepatic glucose produciton
Acts in the ARC by inhibiting gluconeogenesis using vagal efferent nerves to the liver.
What two key things are needed for transduction of the reduction of hepatic glucose production
Alpha7 nicotinic receptors and IL-6 (look at picture)
