{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:55:11Z","timestamp":1791215711007,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,11]],"date-time":"2008-12-11T00:00:00Z","timestamp":1228953600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:p>In response to stress, some people lose while others gain weight. This is believed to be due to either increased \u03b2\u2010adrenergic activation, the body's main fat\u2010burning mechanism, or increased intake of sugar\u2010 and fat\u2010rich \u201ccomfort foods.\u201d A high\u2010fat, high\u2010sugar (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. <jats:italic>In vitro<\/jats:italic>, when \u201cstressed\u201d with dexamethasone, sympathetic neurons shift toward expressing more NPY, which stimulates endothelial cell (angiogenesis) and preadipocyte proliferation, differentiation, and lipid\u2010filling (adipogenesis) by activating the same NPY\u2010Y2 receptors (Y2Rs). <jats:italic>In vivo<\/jats:italic>, chronic stress, consisting of cold water or aggression in HFS\u2010fed 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\u2010like symptoms with abdominal obesity, inflammation, hyperlipidemia, hyperinsulinemia, glucose intolerance, hepatic steatosis, and hypertension. Remarkably, local intra\u2010fat Y2R inhibition pharmacologically or via adenoviral Y2R knock\u2010down reverses or prevents fat accumulation and metabolic complications. These studies demonstrated for the first time that chronic stress, via the NPY\u2010Y2R pathway, amplifies and accelerates diet\u2010induced obesity and the metabolic syndrome. Our findings also suggest the use of local administration of Y2R antagonists for treatment of obesity and NPY\u2010Y2 agonists for fat augmentation in other clinical applications.<\/jats:p>","DOI":"10.1196\/annals.1410.035","type":"journal-article","created":{"date-parts":[[2009,11,6]],"date-time":"2009-11-06T14:56:38Z","timestamp":1257519398000},"page":"232-237","source":"Crossref","is-referenced-by-count":134,"title":["Chronic Stress, Combined with a High\u2010Fat\/High\u2010Sugar Diet, Shifts Sympathetic Signaling toward Neuropeptide Y and Leads to Obesity and the Metabolic Syndrome"],"prefix":"10.1196","volume":"1148","author":[{"given":"Lydia E.","family":"Kuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Czarnecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna B.","family":"Kitlinska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason U.","family":"Tilan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kvet\u0148ansk\u00fd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zofia","family":"Zukowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,11]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1934666100"},{"key":"e_1_2_9_3_2","first-page":"S8","article-title":"Novel treatments for obesity","volume":"12","author":"Ludwig D.S.","year":"2003","journal-title":"Asia. 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