ABSTRACT: Obesity-linked metabolic disease is associated with the recruitment of classically activated macrophages into adipose tissue and the reprogramming of adipocyte mitochondrial metabolism. Inflammatory cytokines lead to down regulation of anti-oxidant systems, increased oxidative stress, and the production of reactive lipid aldehydes that non-enzymatically alkylate the side chains of cysteine, histidine or lysine residues in a reaction termed protein carbonylation. Reactive lipid aldehydes and their derivatives are detoxified via a variety of phase I and phase II systems and when antioxidant defenses are compromised or oxidative conditions are increased due to inflammation protein carbonylation is increased. The resulting modification has been implicated as causative in a variety of metabolic states including neurodegeneration, muscle wasting, insulin resistance and aging. Proteomic analysis of adipocyte mitochondria reveals that critical components of the electron transport chain, TCA cycle and branch chain amino acid metabolism are highly carbonylated in response to inflammatory conditions and that carbonylation re-programs adipocyte mitochondrial metabolism that in turn affects glucose transport, lipolysis, gene expression and protein secretion. Such studies suggest that oxidative stress-dependent mitochondrial re-programming is mechanistically linked to protein carbonylation and anti-oxidant therapies may be beneficial towards activating adipocyte metabolism in the obese state. Supported by NIH DK084669 to DAB and the Minnesota Obesity Center (NIH P30DK050456).