V A Constant1, A Gagnon, A Landry, A Sorisky. 1. Department of Medicine and of Biochemistry, University of Ottawa, Ottawa Health Research Institute, Ottawa Hospital, Ottawa, ON, Canada.
Abstract
AIMS/HYPOTHESIS: In obesity, a limited adipogenic capacity may promote adipocyte hypertrophy and increase the risk of insulin resistance and type 2 diabetes. Recent data indicate that macrophages reside within adipose tissue in obese rodents and humans. We hypothesised that secreted macrophage factors may inhibit adipogenesis. MATERIALS AND METHODS: Conditioned media from cultured murine J774 or human THP-1 macrophages were collected, and added to either murine 3T3-L1 preadipocytes or human abdominal stromal preadipocytes from subcutaneous or omental fat depots. RESULTS: Macrophage-conditioned medium (MacCM) strongly inhibited 3T3-L1 adipogenesis. Dose-response studies with J774-MacCM revealed that 80 and 100% of J774-MacCM completely suppressed triacylglycerol accumulation as well as the induction of fatty acid synthase, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, and adiponectin. Similar inhibitory effects on 3T3-L1 preadipocytes were observed with THP-1-MacCM. Differentiation of human abdominal subcutaneous stromal preadipocytes was moderately reduced (subcutaneous>omental) by J744-MacCM. In contrast, the differentiation of both subcutaneous and omental stromal preadipocytes was completely inhibited by THP-1-MacCM, as determined on the basis of morphology and triacylglycerol accumulation, as well as fatty acid synthase and adiponectin protein expression. CONCLUSIONS/ INTERPRETATION: Secreted macrophage products inhibit the differentiation of 3T3-L1 preadipocytes as well as human abdominal stromal preadipocytes.
AIMS/HYPOTHESIS: In obesity, a limited adipogenic capacity may promote adipocyte hypertrophy and increase the risk of insulin resistance and type 2 diabetes. Recent data indicate that macrophages reside within adipose tissue in obese rodents and humans. We hypothesised that secreted macrophage factors may inhibit adipogenesis. MATERIALS AND METHODS: Conditioned media from cultured murine J774 or humanTHP-1 macrophages were collected, and added to either murine 3T3-L1 preadipocytes or human abdominal stromal preadipocytes from subcutaneous or omental fat depots. RESULTS: Macrophage-conditioned medium (MacCM) strongly inhibited 3T3-L1 adipogenesis. Dose-response studies with J774-MacCM revealed that 80 and 100% of J774-MacCM completely suppressed triacylglycerol accumulation as well as the induction of fatty acid synthase, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, and adiponectin. Similar inhibitory effects on 3T3-L1 preadipocytes were observed with THP-1-MacCM. Differentiation of human abdominal subcutaneous stromal preadipocytes was moderately reduced (subcutaneous>omental) by J744-MacCM. In contrast, the differentiation of both subcutaneous and omental stromal preadipocytes was completely inhibited by THP-1-MacCM, as determined on the basis of morphology and triacylglycerol accumulation, as well as fatty acid synthase and adiponectin protein expression. CONCLUSIONS/ INTERPRETATION: Secreted macrophage products inhibit the differentiation of 3T3-L1 preadipocytes as well as human abdominal stromal preadipocytes.
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