title: An inflammatory micro-environment promotes human adipocyte apoptosis.
abstract: Obesity-associated macrophage infiltration into adipose tissue is responsible for both local and systemic inflammation. Recent findings suggest fat cell apoptosis as an initiator of macrophage recruitment. Here, we investigated the effects of an inflammatory micro-environment on fat cells using human THP-1 macrophages and SGBS adipocytes. Macrophage-secreted factors induced insulin resistance, inhibited insulin-stimulated Akt phosphorylation, and induced apoptosis of adipocytes. The apoptosis-inducing effect was even more pronounced in direct co-cultures of adipocytes and macrophages. Our data suggest a link between insulin resistance and apoptosis sensitivity. Accordingly, pharmacological and genetic inhibition of insulin signaling at the level of Akt2 sensitized adipocytes to apoptosis induction by macrophage-secreted factors. In conclusion, we describe here a novel interaction of macrophages and fat cells, i.e. induction of apoptosis. Our data suggest a feed-forward cycle in which macrophages further drive the inflammatory process by inducing insulin resistance and concomitant apoptosis of adipocytes.
authors.affiliation: Division of Pediatric Endocrinology, Diabetes and Obesity Unit, Department of Pediatrics and Adolescent Medicine, Ulm University, Eythstr. 24, 89075 Ulm, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Keuper
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Michael R
authors.initials: MR
authors.lastname: Schön
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Anna
authors.initials: A
authors.lastname: Dzyakanchuk
authors.forename: Kurt
authors.initials: K
authors.lastname: Amrein
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D039521:CD11c Antigen / Q000378:metabolism; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D002867:Chromones; D017077:Culture Media, Conditioned; D016207:Cytokines; D007328:Insulin; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt