AGING EFFECT ON PREADIPOCYTE DIFFERENTIATION

Project: Research project

Description

DESCRIPTION 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.
StatusActive
Effective start/end date5/15/973/31/21

Funding

  • National Institutes of Health: $322,000.00
  • National Institutes of Health
  • National Institutes of Health: $457,472.00
  • National Institutes of Health: $300,875.00
  • National Institutes of Health: $321,417.00
  • National Institutes of Health: $322,000.00
  • National Institutes of Health: $260,765.00
  • National Institutes of Health: $322,000.00
  • National Institutes of Health: $417,790.00
  • National Institutes of Health
  • National Institutes of Health: $309,755.00
  • National Institutes of Health: $133,420.00
  • National Institutes of Health: $283,850.00
  • National Institutes of Health: $98,188.00
  • National Institutes of Health: $272,155.00
  • National Institutes of Health: $283,850.00
  • National Institutes of Health: $295,308.00

Fingerprint

Adipogenesis
CCAAT-Enhancer-Binding Protein-alpha
Fats
Adipocytes
Cytokines
CCAAT-Enhancer-Binding Protein-beta
Fatty Acids
Physiological Stress
Tumor Necrosis Factor-alpha
Phenotype
PPAR gamma
Mitogen-Activated Protein Kinase 11
Mitogen-Activated Protein Kinase 8
Obesity
Transfection
Fatty Acid-Binding Proteins
Messenger RNA
Organized Financing
Lipolysis
Atherosclerosis

ASJC

  • Medicine(all)