Chemical genetic identification of the histamine H1 receptor as a stimulator of insulin-induced adipogenesis.
A large collection of bioactive compounds with diverse biological effects can be used as probes to elucidate new biological mechanisms that influence a particular cellular process. Here we analyze the effects of 880 well-known small-molecule bioactives or drugs on the insulin-induced adipogenesis of 3T3-L1 fibroblasts, a cell-culture model of fat cell differentiation. Our screen identified 86 compounds as modulators of the adipogenic differentiation of 3T3-L1 cells. Examination of their chemical and pharmacological information revealed that antihistamine drugs with distinct chemical scaffolds inhibit differentiation. Histamine H1 receptor is expressed in 3T3-L1 cells, and its knockdown by small interfering RNA impaired the insulin-induced adipogenic differentiation. Histamine receptors and histamine-like biogenic amines may play a role in inducing adipogenesis in response to insulin.
The Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Yoshinori
Y
Kawazoe
Satoshi
S
Tanaka
Motonari
M
Uesugi
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D017931:DNA Primers; D006632:Histamine / Q000502:physiology; D007328:Insulin / Q000502:physiology*; D051379:Mice; D034741:RNA, Small Interfering / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D007328:Insulin; D034741:RNA, Small Interfering; D011969:Receptors, Histamine H1; D006632:Histamine