Obesity Flashcards
What factors contribute to the development of obesity?
Reduced physical activity and increased food intake.
How does the VMH coordinate annorexigenic and orezigenic signals?
The VMH sends orexigenic/annorexigenic signals to the lateral hypothalamic area and the PVN. These send afferent signals to the locus coerulus, the nucleus tractus solitarius and the dorsal motor nucleus of the vagus nerve.
LC feedsback to the VMH and the LC+NTS innervate the adipocytes to increase lipolysis.
The DMV innervates visceral organs (pancreas, s.i. stomach and liver) to promote energy storage.
What hormones are involved in the control of lipolysis and signalling energy intake?
Insulin decreases lipolysis and feedsback to the VMH
Leptin from fat cells feeds back to VMH
Peptide-YY (s.i) and grhelin (stomach) also feed to the VMH to signal the fed state.
Other than physical activity, what else affects energy expenditure?
BMR and adaptive thermogenesis.
How does hormonal stimulation lead to adipogenesis?
C/EBPb/d activate PPARg which also activates CEBPa.
CEBPa and ADD1/SREBP1 activate PPARg.
All of these TFs lead to fat cell specific gene expression.
How does brown fat differentiate?
PRDM16-C + C/EBPb activate PGC1a and PPARg in Myf5-positive myoblastic precursors which induce brown fat gene expression.
cAMP and FoxC2 have a positive effect on PGC1a/PPARg
several other TFs have a negative effect on PGC1a.
PRDM16-C coactivates PPARg and PGC1a.
What cells end up as white adipose tissue?
Myf5-negative myoblastic precursors.
How can these cells end up as brown fat?
Pre-determined populations may form brown fat
White pre-adipocytes may turn directly to brown fat
White adipocytes may transdifferentiate into brown fat cells.
Where is the FTO gene located?
On chromosome 16 in humans
Why is FTO thought to have a role in DNA repair?
It can methylate single stranded DNA and RNA. It is also closely related to a bacterial DNA repair enzyme
What domains of FTO need to interact for it to be catylitically active?
Carboxy and amino terminal domains.
What is seen in FTO k/o mice?
Growth retardation with decreased fat and lean body mass but an increased metabolic rate and food intake.
How does FTO regulate food intake?
It increases in the fed state but decreases in the fasted stat in the ARC. It allows bidirectional control of food intake.
What are FTO mutations in humans associated with?
Allelic mutations seem to predispose to increased food intake. Catalytic site mutations are lethal, suggesting it is involved in the development of many organ systems.
What does TMEM18 stand for?
Transmembrane protein 18.
