AGING EFFECT ON PREADIPOCYTE DIFFERENTIATION

$272,155R01FY2000AGNIH

Boston Medical Center, Boston MA

Investigators

Linked publications, trials & patents

Paper 38995093 Paper 37879300 Paper 37380899 Paper 37154858 Paper 36809340 Paper 36170432 Paper 35713877 Paper 35292270 Paper 35015744 Paper 34873338 Paper 34531331 Paper 34514190 Paper 34391091 Paper 34375437 Paper 34135081 Paper 33858824 Paper 33688395 Paper 33470505 Paper 33144212 Paper 32023351 Paper 31971661 Paper 31485887 Paper 31356770 Paper 31088710 Paper 30913313 Paper 30907060 Paper 30854802 Paper 30737259 Paper 30612898 Paper 30601138 Paper 30508396 Paper 29988130 Paper 29176033 Paper 28869295 Paper 28825716 Paper 28802066 Paper 28416161 Paper 28230051 Paper 27927801 Paper 27721062 Paper 27591120 Paper 27507649 Paper 27241018 Paper 26931808 Paper 26924669 Paper 26687007 Paper 26578790 Paper 26106186 Paper 25864718 Paper 25754370 Paper 25446976 Paper 25445398 Paper 25070626 Paper 25063774 Paper 25053585 Paper 24992635 Paper 24848532 Paper 24802126 Paper 23583168 Paper 23512893 Paper 23240002 Paper 23237984 Paper 22958919 Paper 22911724 Paper 22677645 Paper 22451473 Paper 22048312 Paper 22009727 Paper 21467195 Paper 21436255 Paper 21173238 Paper 21164220 Paper 20921416 Paper 20864777 Paper 20713685 Paper 20701600 Paper 20555032 Paper 20300084 Paper 20110661 Paper 20106964 Paper 17911345 Paper 17507194 Paper 17148751 Paper 16985259 Paper 16936206 Paper 16754681 Paper 15383371 Paper 12424865 Paper 12175476 Paper 11959668 Paper 11353682 Paper 11158926 Paper 10880345

Abstract

DESCRIPTION (Adapted from the Applicant's Abstract): It is hypothesized that C/EBPalpha, a key transcription factor that controls both initiation of adipogenesis and maintenance of the fat cell phenotype, plays a central role in the age-related decrease in preadipocyte differentiation and lipid accumulation. Specific Aim 1 of the investigators is to determine effects of aging on expression and activity of C/EBPalpha and transcription factors regulating its expression during preadipocyte differentiation. They will define changes in the mRNA and protein levels and functional properties of C/EBPalpha and potential C/EBPalpha regulators (CHOP, C/EBPbeta-LIP and LAP, C/EBPbeta, CUP, c-myc, PPARy:RXRa) using Northern blot, Western blot and in vitro DNA binding assays respectively in differentiating preadipocytes from 3 and 24m rats. These experiments will 1) establish temporal relationships among age-related changes in expression of C/EBPalpha, C/EBPalpha regulators, selected differentiation-dependent target genes, and lipid accumulation (TG/DNA ratio) and 2) identify those C/EBPalpha regulators which change in amount or activity during aging. Specific Aim 2 is to determine whether age-related changes in preadipocyte differentiation are caused directly by alterations in C/EBPalpha and C/EBPalpha regulator levels and/or activity. Two experimental approaches will be used: 1) treatment of preadipocytes with agents known to alter C/EBPalpha expression (TNFa converting enzyme inhibitors, glucocorticoids, SB203580, thiazolidinediones) and 2) transfection of appropriate DNA constructs to alter levels of C/EBPalpha and those C/EBPalpha regulators identified in Specific Aim 1 that influence related changes in expression. Specific Aim 3 is to assess the relevance of their findings to humans. They will determine in human preadipocytes whether changes in differentiation-dependent mRNA levels are blunted with age and if C/EBPalpha expression and activity decline with age.

View original record on NIH RePORTER →