AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue.

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

Cell

journal_title

Cell

authors

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,Wunder

doi

10.1016/j.cell.2016.02.044

subject

Has Abstract

pub_date

2016-03-24 00:00:00

pages

125-138

issue

1

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(16)30194-5

journal_volume

165

pub_type

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