Premium
Chronic Stress, Combined with a High‐Fat/High‐Sugar Diet, Shifts Sympathetic Signaling toward Neuropeptide Y and Leads to Obesity and the Metabolic Syndrome
Author(s) -
Kuo Lydia E.,
Czarnecka Magdalena,
Kitlinska Joanna B.,
Tilan Jason U.,
Kvetňanský Richard,
Zukowska Zofia
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1410.035
Subject(s) - neuropeptide y receptor , obesity , endocrinology , medicine , sugar , neuropeptide , metabolic syndrome , sympathetic activity , chronic stress , sympathetic nervous system , chemistry , food science , receptor , heart rate , blood pressure
In response to stress, some people lose while others gain weight. This is believed to be due to either increased β‐adrenergic activation, the body's main fat‐burning mechanism, or increased intake of sugar‐ and fat‐rich “comfort foods.” A high‐fat, high‐sugar (HFS) diet alone, however, cannot account for the epidemic of obesity, and chronic stress alone tends to lower adiposity in mice. Here we discuss how chronic stress, when combined with an HFS diet, leads to abdominal obesity by releasing a sympathetic neurotransmitter, neuropeptide Y (NPY), directly into the adipose tissue. In vitro , when “stressed” with dexamethasone, sympathetic neurons shift toward expressing more NPY, which stimulates endothelial cell (angiogenesis) and preadipocyte proliferation, differentiation, and lipid‐filling (adipogenesis) by activating the same NPY‐Y2 receptors (Y2Rs). In vivo , chronic stress, consisting of cold water or aggression in HFS‐fed mice, stimulates the release of NPY and the expression of Y2Rs in visceral fat, increasing its growth by 50% in 2 weeks. After 3 months, this results in metabolic syndrome‐like symptoms with abdominal obesity, inflammation, hyperlipidemia, hyperinsulinemia, glucose intolerance, hepatic steatosis, and hypertension. Remarkably, local intra‐fat Y2R inhibition pharmacologically or via adenoviral Y2R knock‐down reverses or prevents fat accumulation and metabolic complications. These studies demonstrated for the first time that chronic stress, via the NPY‐Y2R pathway, amplifies and accelerates diet‐induced obesity and the metabolic syndrome. Our findings also suggest the use of local administration of Y2R antagonists for treatment of obesity and NPY‐Y2 agonists for fat augmentation in other clinical applications.