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

VL - 12

SP - 1140

EP - 1149

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 8

ER -