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Author Karagiannides, Iordanes
Title Alterations in adipogenic transcription factor expression lead to reduced preadipocyte differentiation with aging
book jacket
Descript 199 p
Note Source: Dissertation Abstracts International, Volume: 64-08, Section: B, page: 3672
Major Professor: James L. Kirkland
Thesis (Ph.D.)--Boston University, 2004
Aging is associated with a substantial decline in body weight, fat mass and percent body fat. Loss of fat tissue predisposes the elderly to chronic skin ulcers, disturbances of body temperature, and decreased energy reserves in the face of chronic illness. It can also result in glucose intolerance, potentially contributing to the development of type II diabetes in elderly, lean patients. Since adipocyte responsiveness to lipolytic agents declines and adipocyte numbers increase with aging, these changes in fat mass and percent body fat in old individuals may be due to the reduced capacity of preadipocytes to accumulate lipid. We have investigated the effects of aging on transcription factors involved in adipogenesis. C/EBPalpha and PPARgamma adipogenic transcription factors are essential for maintenance of the differentiated fat cell phenotype. We observed that the expression of both C/EBPalpha and PPARgamma, as well as their downstream target aP2, decreased with increasing age. Furthermore, the levels of C/EBPbeta and C/EBdelta, which trans-activate the promoters of both C/EBPalpha and PPARgamma, also decreased with aging. Augmentation of adipogenic transcription factor expression in rat preadipocytes from old animals restored their adipogenic potential. RXRalpha expression was unaffected by aging. In contrast, the expression of upstream, anti-adipogenic factors, such as C/EBPbeta-LIP, CHOP, and CUGBP, increased with aging. Overexpression of C/EBPbeta-LIP in preadipocytes from young animals abolished their ability to differentiate. The anti-adipogenic potential of CUGBP, which causes C/EBPbeta-LIP production from C/EBPbeta mRNA, was demonstrated for the first time. Thus, reduced differentiation with aging is due to specific effects of aging on the expression of preadipocyte transcription factors. Aging is associated with decreased expression of adipogenic transcription factors and increased expression of anti-adipogenic factors. The ability of predipocytes from old animals to regain their adipogenic potential after the induction of either C/EBPalpha or PPARgamma expression suggests that effects upstream of adipogenic regulator expression are responsible for reduced adipogenesis with aging. The association of the anti-adipogenic factors studied here with stress responses, as well as the induction of CUGBP by TNFalpha, suggest that activation of cellular stress responses may be the means through which aging decreases adipogenesis
School code: 0017
Host Item Dissertation Abstracts International 64-08B
Subject Biology, Molecular
Biology, Cell
Health Sciences, Pathology
Alt Author Boston University
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