Abstract:
:Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP → LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP → anterior bed nucleus of the stria terminalis (aBNST)vl projections, distinct from AgRP → aBNSTdm projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis.
journal_name
Celljournal_title
Cellauthors
Steculorum SM,Ruud J,Karakasilioti I,Backes H,Engström Ruud L,Timper K,Hess ME,Tsaousidou E,Mauer J,Vogt MC,Paeger L,Bremser S,Klein AC,Morgan DA,Frommolt P,Brinkkötter PT,Hammerschmidt P,Benzing T,Rahmouni K,Wunderdoi
10.1016/j.cell.2016.02.044subject
Has Abstractpub_date
2016-03-24 00:00:00pages
125-138issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(16)30194-5journal_volume
165pub_type
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