Pathobiologie/Pathobiochemie Teil 2 Lektion 8 8.11.10 ... - Alex Eberle

54
Adipositas und Mutationen im MC4-R Gen (1)
Model of homeostatic circuit regulating
energy balance through the
melanocortin 4 receptor (MC4R)
Increased adiposity leads to increased
leptin production in fat tissue. Leptin
stimulates neurons in the arcuate
nucleus of the hypothalamus that
coexpress the anorexigenic hormones
melanocyte-stimulating hormone (α-
MSH, a cleavage product of proopiomelanocortin
[POMC]) and cocaine- and
amphetamine-regulated transcript.
Leptin also inhibits neurons in the
arcuate nucleus that coexpress the
orexigenic hormones agouti-related
protein and neuropeptide Y. The
neurons in the arcuate nucleus project to
other regions of the hypothalamus
(including the paraventricular nucleus
and the lateral hypothalamic area –
parafornical area), where α-MSH binds
to its receptor, MC4R, resulting in an upregulation
of anorexigenic effectors such
as corticotropin-releasing hormone
(CRH) and thyrotropin-releasing
hormone (TRH) and a down-regulation
of orexigenic effectors such as melaninconcentrating
hormone (MCH) and
orexin. Agouti-related protein acts as an
antagonist of MC4R.
08/11/10 Pathobiologie - HS 2010 - Lektion 8 54