title: Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors.
abstract: Recent studies suggest that angiotensin II (Ang II) plays a role in the adipogenesis of murine preadipocytes. Here, we examined the role of Ang II for the differentiation of primary cultured human preadipocytes. Preadipocytes were isolated from human adipose tissue and stimulated to differentiate. Quantitation of gene expression during adipogenesis was performed for renin-angiotensin system (RAS) genes. The influence of the RAS on adipogenic differentiation was investigated by addition of either angiotensinogen (AGT), Ang II, or angiotensin receptor antagonists to the differentiation medium. We also examined the influence of adipocytes on adipogenesis by co-culture experiments. Expression of the RAS genes AGT, renin, angiotensin-converting enzyme, and Ang II type 1 receptor increased during adipogenesis. Stimulation of the Ang II type 1 receptor by Ang II reduced adipose conversion, whereas blockade of this receptor markedly enhanced adipogenesis. Adipocytes were able to inhibit preadipocyte differentiation in the co-culture, and this effect was abolished by blockade of the Ang II type 1 receptor. This finding points to a functional role of the RAS in the differentiation of human adipose tissue. Because AGT secretion and Ang II generation are characteristic features of adipogenesis, we postulate a paracrine negative-feedback loop that inhibits further recruitment of preadipocytes by maturing adipocytes.
authors.affiliation: Max Delbrück Center for Molecular Medicine, HELIOS Klinikum-Berlin, Franz Volhard Clinic, Medical Faculty of the Charité, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Janke
authors.forename: Stefan
authors.initials: S
authors.lastname: Engeli
authors.forename: Kerstin
authors.initials: K
authors.lastname: Gorzelniak
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Arya M
authors.initials: AM
authors.lastname: Sharma
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D015870:Gene Expression; D006801:Humans; D000077405:Irbesartan; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics; D013234:Stem Cells / Q000166:cytology*; D013777:Tetrazoles / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D018160:Receptors, Cytoplasmic and Nuclear; D013777:Tetrazoles; D014157:Transcription Factors; D000808:Angiotensinogen; D000804:Angiotensin II; D002216:Captopril; D000077405:Irbesartan