Excess visceral adiposity induces alterations in mitochondrial function and energy metabolism in XXXX .

@entity1 @entity897 @entity28 @entity5 @entity535 @entity26 @entity17341 @entity1144 @entity418 @entity420 @entity855 @entity2383
BACKGROUND: @entity1144 has a strong association with both the incidence and mortality of @entity420 ( @entity420 ). Alterations in mitochondrial function and energy metabolism is an emerging hallmark of @entity5 , however, the potential role that @entity28 plays in driving these alterations in @entity420 is currently unknown. METHODS: Adipose conditioned media (ACM) was prepared from visceral adipose tissue taken from computed tomography-determined viscerally- @entity28 and non- @entity28 @entity1 . Mitochondrial function in @entity420 cell lines was assessed using fluorescent probes, mitochondrial gene expression was assessed using qPCR-based gene arrays and intracellular @entity855 levels were determined using a luminescence-based kit. Glycolysis and oxidative phosphophorylation was measured using Seahorse XF technology and metabolomic analysis was performed using 1H NMR. Expression of metabolic markers was assessed in @entity420 @entity5 biopsies by qPCR. RESULTS: ACM from @entity28 @entity1 significantly increased mitochondrial mass and mitochondrial membrane potential in @entity420 cells, which was significantly associated with visceral fat area, and was coupled with a significant decrease in reactive @entity26 species. This @entity2383 was accompanied by altered expression of 19 mitochondrial-associated genes and significantly reduced intracellular @entity855 levels. ACM from @entity28 @entity1 induced a metabolic shift to glycolysis in @entity420 cells, which was coupled with significantly increased sensitivity to the glycolytic inhibitor @entity897 . Metabolomic profiling demonstrated an altered glycolysis and @entity535 -related signature in ACM from @entity28 @entity1 . In @entity418 , expression of the glycolytic marker @entity17341 was significantly positively associated with @entity28 . CONCLUSION: This study demonstrates for the first time that ACM from viscerally- @entity28 @entity1 elicits an altered metabolic profile and can drive @entity2383 and altered energy metabolism in @entity420 cells in vitro. In vivo, in @entity420 @entity1 @entity5 , expression of the glycolytic enzyme @entity17341 is positively associated with @entity28 .
