Loss of Mfn1 but not Mfn2 enhances adipogenesis.

Loss of Mfn1 but not Mfn2 enhances adipogenesis.

Blog Article

ObjectiveA biallelic missense mutation in mitofusin 2 (MFN2) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles in adipocyte differentiation, growth and/or survival.In this study, we aimed to document the impact of loss of mitofusin 1 (Mfn1) or 2 (Mfn2) on adipogenesis in cultured cells.MethodsWe characterised adipocyte differentiation of wildtype (WT), Mfn1-/- and Mfn2-/- mouse embryonic fibroblasts (MEFs) and 3T3-L1 Hair Clips preadipocytes in which Mfn1 or 2 levels were reduced using siRNA.

ResultsMfn1-/- MEFs displayed striking fragmentation of the mitochondrial network, with surprisingly enhanced propensity to differentiate into adipocytes, as assessed by lipid accumulation, expression of adipocyte markers (Plin1, Tanks/Jerseys Fabp4, Glut4, Adipoq), and insulin-stimulated glucose uptake.RNA sequencing revealed a corresponding pro-adipogenic transcriptional profile including Pparg upregulation.Mfn2-/- MEFs also had a disrupted mitochondrial morphology, but in contrast to Mfn1-/- MEFs they showed reduced expression of adipocyte markers.

Mfn1 and Mfn2 siRNA mediated knockdown studies in 3T3-L1 adipocytes generally replicated these findings.ConclusionsLoss of Mfn1 but not Mfn2 in cultured pre-adipocyte models is pro-adipogenic.This suggests distinct, non-redundant roles for the two mitofusin orthologues in adipocyte differentiation.