Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome.
The relationship between stress and obesity remains elusive. In response to stress, some people lose weight, whereas others gain. Here we report that stress exaggerates diet-induced obesity through a peripheral mechanism in the abdominal white adipose tissue that is mediated by neuropeptide Y (NPY). Stressors such as exposure to cold or aggression lead to the release of NPY from sympathetic nerves, which in turn upregulates NPY and its Y2 receptors (NPY2R) in a glucocorticoid-dependent manner in the abdominal fat. This positive feedback response by NPY leads to the growth of abdominal fat. Release of NPY and activation of NPY2R stimulates fat angiogenesis, macrophage infiltration, and the proliferation and differentiation of new adipocytes, resulting in abdominal obesity and a metabolic syndrome-like condition. NPY, like stress, stimulates mouse and human fat growth, whereas pharmacological inhibition or fat-targeted knockdown of NPY2R is anti-angiogenic and anti-adipogenic, while reducing abdominal obesity and metabolic abnormalities. Thus, manipulations of NPY2R activity within fat tissue offer new ways to remodel fat and treat obesity and metabolic syndrome.
Kuo
Lydia E
LE
Department of Physiology & Biophysics, Georgetown University Medical Center, 3900 Reservoir Rd. NW, BSB 234, Washington, DC 20057, USA.
Kitlinska
Joanna B
JB
Tilan
Jason U
JU
Li
Lijun
L
Baker
Stephen B
SB
Johnson
Michael D
MD
Lee
Edward W
EW
Burnett
Mary Susan
MS
Fricke
Stanley T
ST
Kvetnansky
Richard
R
Herzog
Herbert
H
Zukowska
Zofia
Z
D041721:3T3-L1 Cells; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D003080:Cold Temperature; D004032:Diet; D004041:Dietary Fats; D017353:Gene Deletion; D005786:Gene Expression Regulation; D008297:Male; D024821:Metabolic Syndrome; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000235:genetics; D013312:Stress, Physiological / Q000378:metabolism*; D015854:Up-Regulation
D004041:Dietary Fats; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor