Objective: Growth differentiation factor (GDF15) is multifunctional member of the TGF-beta superfamily. GDF15, a secretory cytokine, can be induced in multiple cellular stimuli such as mitochondrial oxidative phosphorylation (OxPhos) dysfunction. To verify the role of GD15 in in vivo in the context of adipose mitochondrial OxPhos dysfunction, we have observed GDF15 expression in adipose tissue-specific Crif1, an essential factor of mitochondrial OxPhos biogenesis,-deficient mice. Methods: To establish adipose tissue-specific mitochondrial OxPhos dysfunction, we generated adipose tissue-specific Crif1-dificient mice by crossing transgenic adiponectin-cre mice with floxed Crif1 mice (Crif1f/f, adipoq-cre). Results: Adipose tissue-specific Crif1 deficient mice showed mitochondrial OxPhos dysfunction and mild insulin resistance. Mitochondrial OxPhos dysfunction induced by adipose tissue-specific Crif1 deficiency increased GDF15 expression in adipose tissue and increased plasma level. In vitro, we were induced to mitochondrial dysfunction by rotenone, oligomycin and CCCP, Mitochondrial inhibitors increased GDF15 expression through activating transcription factor 3 (ATF3)-dependent manner in 3T3-L1 pre/adipocyte cells. Conclusion: Therefore, we suggest that GDF15 is induced in adipose-tissue specific mitochondrial OxPhos dysfunction and might be involved in insulin resistance in mice with adipose-specific mitochondrial OxPhos dysfunction.