TY - JOUR
T1 - Characterization of the inhibitory effect of growth hormone on primary preadipocyte differentiation
AU - Hansen, L. H.
AU - Madsen, B
AU - Teisner, Børge
AU - Nielsen, Jens Høiriis
AU - Billestrup, N
PY - 1998/8
Y1 - 1998/8
N2 - GH exerts adipogenic activity in several preadipocyte cell lines, whereas in primary rat preadipocytes, GH has an antiadipogenic activity. To better understand the molecular mechanism involved in adipocyte differentiation, the expression of adipocyte-specific genes was analyzed in differentiating preadipocytes in response to GH. We found that the expression of both adipocyte determination and differentiation factor 1 (ADD1) and peroxisome proliferator activated receptor gamma(PPARgamma) was induced in preadipocytes during differentiation. In the presence of GH, which markedly inhibited triglyceride accumulation, no reduction in the expression level of ADD1 was observed in response to GH, whereas there was a 50% reduction in the expression of PPARgamma. The DNA binding activity of the PPARgamma/retinoid X receptor-alpha(RXRalpha) to the ARE7 element from the aP2 gene was also reduced by approximately 50% in response to GH. GH inhibited the expression of late markers of adipocyte differentiation, fatty acid synthase, aP2, and hormone-sensitive lipase by 70-80%. The antiadipogenic effect of GH was not affected by the mitogen-activated protein (MAP) kinase/ extracellular-regulated protein (ERK) kinase inhibitor PD 98059, indicating that the mitogen-activated protein kinase pathway was not involved in GH inhibition of preadipocyte differentiation. The expression of preadipocyte factor-1/fetal antigen 1 was decreased during differentiation, and GH treatment prevented this down-regulation of Pref1/FA1. A possible role for Pref-1/FA1 in mediating the antiadipogenic effect of GH was indicated by the observation that FA1 inhibited differentiation as effectively as GH. These data suggest that GH exerts its inhibitory activity in adipocyte differentiation at a step after the induction of ADD1 but before the induction of genes required for terminal differentiation.
AB - GH exerts adipogenic activity in several preadipocyte cell lines, whereas in primary rat preadipocytes, GH has an antiadipogenic activity. To better understand the molecular mechanism involved in adipocyte differentiation, the expression of adipocyte-specific genes was analyzed in differentiating preadipocytes in response to GH. We found that the expression of both adipocyte determination and differentiation factor 1 (ADD1) and peroxisome proliferator activated receptor gamma(PPARgamma) was induced in preadipocytes during differentiation. In the presence of GH, which markedly inhibited triglyceride accumulation, no reduction in the expression level of ADD1 was observed in response to GH, whereas there was a 50% reduction in the expression of PPARgamma. The DNA binding activity of the PPARgamma/retinoid X receptor-alpha(RXRalpha) to the ARE7 element from the aP2 gene was also reduced by approximately 50% in response to GH. GH inhibited the expression of late markers of adipocyte differentiation, fatty acid synthase, aP2, and hormone-sensitive lipase by 70-80%. The antiadipogenic effect of GH was not affected by the mitogen-activated protein (MAP) kinase/ extracellular-regulated protein (ERK) kinase inhibitor PD 98059, indicating that the mitogen-activated protein kinase pathway was not involved in GH inhibition of preadipocyte differentiation. The expression of preadipocyte factor-1/fetal antigen 1 was decreased during differentiation, and GH treatment prevented this down-regulation of Pref1/FA1. A possible role for Pref-1/FA1 in mediating the antiadipogenic effect of GH was indicated by the observation that FA1 inhibited differentiation as effectively as GH. These data suggest that GH exerts its inhibitory activity in adipocyte differentiation at a step after the induction of ADD1 but before the induction of genes required for terminal differentiation.
KW - Adipocytes
KW - Animals
KW - CCAAT-Enhancer-Binding Proteins
KW - Calcium-Calmodulin-Dependent Protein Kinases
KW - Carrier Proteins
KW - Cell Differentiation
KW - Cells, Cultured
KW - DNA-Binding Proteins
KW - Fatty Acid-Binding Proteins
KW - Flavonoids
KW - Gene Expression Regulation
KW - Glycoproteins
KW - Growth Hormone
KW - Insulin
KW - Intercellular Signaling Peptides and Proteins
KW - Male
KW - Membrane Proteins
KW - Myelin P2 Protein
KW - Neoplasm Proteins
KW - Nerve Tissue Proteins
KW - Nuclear Proteins
KW - Phorbol 12,13-Dibutyrate
KW - Rats
KW - Rats, Sprague-Dawley
KW - Receptors, Cytoplasmic and Nuclear
KW - Repressor Proteins
KW - Sterol Regulatory Element Binding Protein 1
KW - Transcription Factors
M3 - Journal article
C2 - 9717840
SN - 0888-8809
VL - 12
SP - 1140
EP - 1149
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 8
ER -