Differential Modulation of 3T3-L1 Adipogenesis Mediated by 11β-Hydroxysteroid Dehydrogenase-1 Levels

Kim, Jaime; Temple, Karla A.; Jones, Sara A.; Meredith, Kimberly N.; Basko, Juliana L.; Brady, Matthew J.

doi:10.1074/jbc.m606197200

Cited by 27 publications

(27 citation statements)

References 46 publications

(41 reference statements)

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“…Alternatively, the overexpressed HSD11B1 might not be properly targeted to the inner face of the ER membrane but directly or indirectly -in ER-derived bodies resulting from an ER overloading/stress -to the cytosol, where it works as a dehydrogenase (Odermatt et al 1999). A study in 3T3-L1 cells, whose HSD11B1 has been silenced by short hairpin RNA constructs (Kim et al 2007), is in line with the aforementioned hypothesis. These authors observed that the re-expression of HSD11B1 at relatively low levels restores the dehydrocorticosterone-induced differentiation, a process that requires the HSD11B1-dependent reductase activity.…”

Section: Discussionsupporting

confidence: 59%

Constant expression of hexose-6-phosphate dehydrogenase during differentiation of human adipose-derived mesenchymal stem cells

Senesi

Marcolongo

Manini

et al. 2008

Journal of Molecular Endocrinology

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The reductase activity of 11b-hydroxysteroid dehydrogenase type 1 (HSD11B1) plays an important role in the growth and differentiation of adipose tissue via the prereceptorial activation of glucocorticoids. This enzyme colocalizes with hexose-6-phosphate dehydrogenase (H6PD) at the luminal surface of the endoplasmic reticulum membrane, and the latter enzyme provides NADPH to the former, which can thus act as an 11b-reductase. It was suggested that, during adipogenesis, the increased expression of H6PD causes a dehydrogenase-to-reductase switch in the activity of HSD11B1. However, only the expression of the HSD11B1 has been extensively studied, and little is known about the expression of H6PD. Here, we investigated the expression and the activity of H6PD in the course of the differentiation of human adipose-derived mesenchymal stem cells (ADMSCs) and murine 3T3-L1 cells. It was found that H6PD is already present in adipose-derived stem cells and in 3T3-L1 fibroblasts even before the induction of adipogenesis. Moreover, mRNA and protein levels, as well as the microsomal H6PD activities remained unchanged during the differentiation. At the same time a great induction of HSD11B1 was observed in both cell types. The observed constant expression of H6PD suggests that HSD11B1 acts as a reductase throughout the adipogenesis process in human ADMSCs and murine 3T3-L1 cells.

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Section: Discussionsupporting

confidence: 59%

Constant expression of hexose-6-phosphate dehydrogenase during differentiation of human adipose-derived mesenchymal stem cells

Senesi

Marcolongo

Manini

et al. 2008

Journal of Molecular Endocrinology

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“…Transcription of 11β-HSD1 in preadipocytes has been shown to be enhanced by glucocorticoids [10,11] and CCAAT enhancer-binding proteins (C/EBP) α and β, transcription factors which play crucial roles in directing the differentiation process [12]. When 11β-HSD1 levels in 3T3-L1 fibroblasts were reduced by RNA interference, differentiation by inactive glucocorticoids was prevented and the expression of adipocyte-specific proteins such as peroxisome proliferator-activated receptor (PPAR) γ and C/EBP α was eventually reduced [13]. Taken together, these data suggest that the expression and activity of 11β-HSD1 may increase in an autocrine and/or paracrine manner during the process of adipogenesis, and that the biological importance of an increase in 11β-HSD1 activity during adipogenesis may be to bring about the differentiation of preadipocytes and initiate adipogenesis in the preadipocytes around them.…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone (GH) or Insulin-like Growth Factor (IGF)-I Represses 11.BETA.-Hydroxysteroid Dehydrogenase Type 1 (HSD1) mRNA Expression in 3T3-L1 Cells and Its Activity in Their Homogenates

et al. 2009

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Abstract.Patients with growth hormone (GH) deficiency (GHD) have a clinical feature of visceral adiposity and it has been reported that these patients have an increased active cortisol (F)/inactive cortisone (E) metabolite ratio. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme expressed in liver and adipose tissue that acts principally as a reductase converting E to F. In the present study, we investigated the effects of GH or IGF-I on the activity of 11β-HSD1 in 3T3-L1 cell homogenates and its mRNA expression. First, we showed that 11β-HSD1 activity and mRNA levels were low in preadipocytes and increased throughout the process of adipogenesis. When fully differentiated adipocytes were treated with GH for various times, the activity of 11β-HSD1 was significantly decreased after 4 h and 8 h but was restored to basal levels after 24 h. After 8 h of GH stimulation, 11β-HSD1 mRNA levels were decreased compared with basal levels. IGF-I treatment of adipocytes resulted in rapid decreases in 11β-HSD1 activity as well as mRNA levels; however, IGF-I treatment for 24 h increased 11β-HSD1 activity. In long-term cultured adipocytes, GH or IGF-I showed only inhibitory effects on 11β-HSD1 activity. In conclusion, 11β-HSD1 activity was suppressed by GH or IGF-I in differentiated adipocytes, probably due to a reduction of 11β-HSD1 mRNA levels. These data suggest that under the conditions of low GH or IGF-I concentrations, 11β-HSD1 activity in adipose tissue is maintained at high levels, leading to an increase in active cortisol that induces adipogenesis and/or lipogenesis. Thus, visceral adiposity in patients with GHD might be related to increased 11β-HSD1 activity.

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“…It has been demonstrated that the differentiation of 3T3-L1 preadipocytes can be induced by both active and inactive glucocorticoids, such as dexamethasone, Acta Pharmacologica Sinica npg corticosterone and 11-DHC, and endogenous 11β-HSD1 oxoreductase activity was expected to be required for differentiation induced by 11-DHC, an inactive glucocorticoid [25] . Thus, we examined the effect of emodin on the differentiation of 3T3-L1 preadipocytes induced by dexamethasone, corticosterone and 11-DHC.…”

Section: Discussionmentioning

confidence: 99%

“…In brief, 3T3-L1 preadipocytes were maintained at ~70% confluence in DMEM supplemented with 10% FBS, 25 …”

Section: Methodsmentioning

confidence: 99%

Emodin, an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, regulates adipocyte function in vitro and exerts anti-diabetic effect in ob/ob mice

et al. 2012

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Aim: Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) with the ability to ameliorate metabolic disorders in diet-induced obese mice. In the present study, we investigated the effects of emodin on adipocyte function and the underlying mechanisms in vitro, and its anti-diabetic effects in ob/ob mice. Methods: 3T3-L1 adipocytes were used for in vitro studies. 11β-HSD1A activity was evaluated with a scintillation proximity assay. The adipogenesis, glucose uptake, lipolysis and adiponectin secretion were investigated in 3T3-L1 adipocytes treated with emodin in the presence of active (corticosterone) or inactive glucocorticoid (11-dehydrocorticosterone). For in vivo studies, ob/ob mice were administered emodin (25 and 50 mg·kg -1 ·d -1 , ip) for 26 d. On the last day of administration, the serum was collected and the mesenteric and perirenal fat were dissected for analyses. Results: Emodin inhibited the 11β-HSD1 activity in 3T3-L1 adipocytes in concentration-and time-dependent manners (the IC 50 values were 7.237 and 4.204 μmol/L, respectively, after 1 and 24 h treatment. In 3T3-L1 adipocytes, emodin (30 μmol/L) suppressed 11-dehydrocorticosterone-induced adipogenesis without affecting corticosterone-induced adipogenesis; emodin (3 μmol/L) reduced 11-dehydrocorticosterone-stimulated lipolysis, but had no effect on corticosterone-induced lipolysis. Moreover, emodin (3 μmol/L) partly reversed the impaired insulin-stimulated glucose uptake and adiponectin secretion induced by 11-dehydrocorticosterone but not those induced by corticosterone. In ob/ob mice, long-term emodin administration decreased 11β-HSD1 activity in mesenteric adipose tissues, lowered non-fasting and fasting blood glucose levels, and improved glucose tolerance. Conclusion: Emodin improves the inactive glucocorticoid-induced adipose tissue dysfunction by selective inhibition on 11β-HSD1 in adipocyte in vitro and improves glycemic control in ob/ob mice.

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Differential Modulation of 3T3-L1 Adipogenesis Mediated by 11β-Hydroxysteroid Dehydrogenase-1 Levels

Cited by 27 publications

References 46 publications

Constant expression of hexose-6-phosphate dehydrogenase during differentiation of human adipose-derived mesenchymal stem cells

Constant expression of hexose-6-phosphate dehydrogenase during differentiation of human adipose-derived mesenchymal stem cells

Growth Hormone (GH) or Insulin-like Growth Factor (IGF)-I Represses 11.BETA.-Hydroxysteroid Dehydrogenase Type 1 (HSD1) mRNA Expression in 3T3-L1 Cells and Its Activity in Their Homogenates

Emodin, an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, regulates adipocyte function in vitro and exerts anti-diabetic effect in ob/ob mice

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