T cell metabolism as interpreted in obesity-associated inflammation

Abstract The appreciation of metabolic regulation of T cell function has exploded over the past decade, as has our understanding of how inflammation fuels comorbidities of obesity, including type 2 diabetes. The likelihood that obesity fundamentally alters T cell metabolism and thus chronic obesity-associated inflammation is high, but studies testing causal relationships remain under-represented. We searched PubMed for key words including mitochondria, obesity, T cell, type 2 diabetes, cristae, fission, fusion, redox, and reactive oxygen species to identify foundational and more recent studies that address these topics or cite foundational work. We investigated primary papers cited by reviews found in these searches, and highlight recent work with >100 citations to illustrate the state of the art in understanding mechanisms that control metabolism and thus function of various T cell subsets in obesity. However, “popularity” of a paper over the first 5 years after publication cannot assess long-term impact; thus some likely important work with fewer citations is also highlighted. We feature studies of human cells, supplementing with studies from animal models that suggest future directions for human cell research. This approach identified gaps in the literature that will need filled before we can estimate efficacy of mitochondria-targeted drugs in clinical trials to alleviate pathogenesis of obesity-associated inflammation.