{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:39:31Z","timestamp":1790933971074,"version":"4.1.0"},"reference-count":74,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:p>Fat depot sizes peak in middle age but decrease by advanced old age. This phenomenon is associated with ectopic fat deposition, decreased adipocyte size, impaired differentiation of preadipocytes into fat cells, decreased adipogenic transcription factor expression, and increased fat tissue inflammatory cytokine generation. To define the mechanisms contributing to impaired adipogenesis with aging, we examined the release of TNF\u03b1, which inhibits adipogenesis, and the expression of CCAAT\/enhancer-binding protein (C\/EBP) homologous protein (CHOP), which blocks activity of adipogenic C\/EBP family members, in preadipocytes cultured from young, middle-aged, and old rats. Medium conditioned by fat tissue, as well as preadipocytes, from old rats impeded lipid accumulation by preadipocytes from young animals. More TNF\u03b1 was released by preadipocytes from old than young rats. Differences in TNF\u03b1-converting enzyme, TNF\u03b1 degradation, or the presence of macrophages in cultures were not responsible. TNF\u03b1 induced rat preadipocyte CHOP expression. CHOP was higher in undifferentiated preadipocytes from old than younger animals. Overexpression of CHOP in young rat preadipocytes inhibited lipid accumulation. TNF\u03b1 short interference RNA reduced CHOP and partially restored lipid accumulation in old rat preadipocytes. CHOP normally increases during late differentiation, potentially modulating the process. This late increase in CHOP was not affected substantially by aging: CHOP was similar in differentiating preadipocytes and fat tissue from old and young animals. Hypoglycemia, which normally causes an adaptive increase in CHOP, was less effective in inducing CHOP in preadipocytes from old than younger animals. Thus increased TNF\u03b1 release by undifferentiated preadipocytes with elevated basal CHOP contributes to impaired adipogenesis with aging.<\/jats:p>","DOI":"10.1152\/ajpendo.00295.2007","type":"journal-article","created":{"date-parts":[[2007,10,3]],"date-time":"2007-10-03T00:28:55Z","timestamp":1191371335000},"page":"E1810-E1819","source":"Crossref","is-referenced-by-count":69,"title":["Increased TNF\u03b1 and CCAAT\/enhancer-binding protein homologous protein with aging predispose preadipocytes to resist adipogenesis"],"prefix":"10.1152","volume":"293","author":[{"given":"Tamara","family":"Tchkonia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Pirtskhalava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Thomou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Cartwright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barton","family":"Wise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iordanes","family":"Karagiannides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Shpilman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy L.","family":"Lash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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