Converting energy storing white adipocytes to energy wasting ‘brite’ ones is now recognized to be feasible and may confer protection against obesity and its related cardiometabolic diseases. Fragments of omental and subcutaneous human adipose tissues were cultured for 7 days with insulin and dexamethasone with or without rosiglitazone (rosi) to induce britening. Rosi caused a metabolic reprograming of the adipocytes including increased rates of basal FA oxidation and the expression of mRNAs and proteins in multiple pathways that modulate FA metabolism, triacylglycerol synthesis, cellular FA trafficking, and mitochondrial oxidative capacity (PGC1a, UCP1, CIDEA, PLIN5, FABP3). Furthermore, these changes were associated with a dramatic remodeling of the surface of the adipocyte lipid droplet (LD) such that clusters of small LDs decorated with mitochondria were formed. Formation of these small LDs was blocked by inhibition of lipolysis and required FA activation and reesterification. Surprisingly, both omental and subcutaneous adipocytes were similarly ‘britened’. A similar remodeling was induced in primary cultures of newly-differentiated human adipocytes and these cells showed higher rates of basal and maximally-stimulated oxygen consumption. Consistent with transcriptome changes in both systems, lipidomics showed increased levels of unsaturated FAs, phospholipid species, and cardiolipins in brite cells. Taken together, these results identify a coordinated metabolic and structural reprogramming of mature human adipocytes toward a more oxidative phenotype. Although rosi has unacceptable clinical side effects, knowledge of the downstream effectors of this metabolic improvement may lead to development of targeted approaches to improve adipocyte and metabolic health and prevent type 2 diabetes in human obesity.


M. Lee: None. S. Jash: None. V. Puri: None. S.K. Fried: None.

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