TY - JOUR
T1 - Glucocorticoid Receptor Signaling Is Not Required for in Vivo Adipogenesis
AU - Bauerle, Kevin T.
AU - Hutson, Irina
AU - Scheller, Erica L.
AU - Harris, Charles A.
N1 - Funding Information:
Financial Support: This work was funded by National Institutes of Health Grants DK106083 (to C.A.H.) and DE024178 (to E.L.S.). K.T.B. was supported by T32 Grant DK007120 to Washington University School of Medicine, the Endocrine Scholar’s Award, and the St. Louis Veterans Affairs Medical Center.
Publisher Copyright:
© 2018 Endocrine Society.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Regulation of adipogenesis is of major interest given that adipose tissue expansion and dysfunction are central to metabolic syndrome. Glucocorticoids (GCs) are important for adipogenesis in vitro. However, establishing a role for GCs in adipogenesis in vivo has been difficult. GC receptor (GR)-null mice die at birth, a time at which wild-type (WT) mice do not have fully developed white adipose depots. We conducted several studies aimed at defining the role of GC signaling in adipogenesis in vitro and in vivo. First, we showed that GR-null mouse embryonic fibroblasts (MEFs) have compromised ability to form adipocytes in vitro, a phenotype that can be partially rescued with a peroxisome proliferator-activated receptor γ 3 agonist. Next, we demonstrated that MEFs are capable of forming de novo fat pads in mice despite the absence of GR or circulating GCs [by bilateral adrenalectomy (ADX)]. However, ADX and GR-null fat pads and their associated adipocyte areas were smaller than those in controls. Second, using adipocyte-specific luciferase reporter mice, we identified adipocytes in both WT and GR-null embryonic day (E)18 mouse embryos. Lastly, positive perilipin staining in WT and GR-null E18 embryos confirmed the presence of early white inguinal and brown adipocytes. Taken together, these results provide compelling evidence that GCs and GR augment but are not required for the development of functional adipose tissue in vivo.
AB - Regulation of adipogenesis is of major interest given that adipose tissue expansion and dysfunction are central to metabolic syndrome. Glucocorticoids (GCs) are important for adipogenesis in vitro. However, establishing a role for GCs in adipogenesis in vivo has been difficult. GC receptor (GR)-null mice die at birth, a time at which wild-type (WT) mice do not have fully developed white adipose depots. We conducted several studies aimed at defining the role of GC signaling in adipogenesis in vitro and in vivo. First, we showed that GR-null mouse embryonic fibroblasts (MEFs) have compromised ability to form adipocytes in vitro, a phenotype that can be partially rescued with a peroxisome proliferator-activated receptor γ 3 agonist. Next, we demonstrated that MEFs are capable of forming de novo fat pads in mice despite the absence of GR or circulating GCs [by bilateral adrenalectomy (ADX)]. However, ADX and GR-null fat pads and their associated adipocyte areas were smaller than those in controls. Second, using adipocyte-specific luciferase reporter mice, we identified adipocytes in both WT and GR-null embryonic day (E)18 mouse embryos. Lastly, positive perilipin staining in WT and GR-null E18 embryos confirmed the presence of early white inguinal and brown adipocytes. Taken together, these results provide compelling evidence that GCs and GR augment but are not required for the development of functional adipose tissue in vivo.
UR - http://www.scopus.com/inward/record.url?scp=85046752263&partnerID=8YFLogxK
U2 - 10.1210/en.2018-00118
DO - 10.1210/en.2018-00118
M3 - Article
C2 - 29579167
AN - SCOPUS:85046752263
VL - 159
SP - 2050
EP - 2061
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 5
ER -