期刊
CELL
卷 165, 期 1, 页码 125-138出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.02.044
关键词
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资金
- DFG [BR 1492/7-1, BE2212, SFB635]
- DFG within the framework of the TRR134
- DFG within Excellence Initiative by German Federal Government (CECAD)
- DFG within Excellence Initiative by German State Government (CECAD)
- Helmholtz Alliance (Imaging and Curing Environmental Metabolic Diseases [ICEMED])
- Helmholtz Association
- European Union [266408]
- US NIH [HL084207]
- American Heart Association [14EIA18860041]
- University of Iowa Fraternal Order of Eagles Diabetes Research Center
- University of Iowa Center for Hypertension Research
- Humboldt-Bayer program of the Alexander Von Humboldt foundation
- CECAD
- Swedish Research Council [2013-530]
- EMBO fellowship
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 -> aBNST(dm) 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.
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