RESUMO
Brown adipose tissue (BAT) regulates metabolic physiology. However, nearly all mechanistic studies of BAT protein function occur in a single inbred mouse strain, which has limited the understanding of generalizable mechanisms of BAT regulation over physiology. Here, we perform deep quantitative proteomics of BAT across a cohort of 163 genetically defined diversity outbred mice, a model that parallels the genetic and phenotypic variation found in humans. We leverage this diversity to define the functional architecture of the outbred BAT proteome, comprising 10,479 proteins. We assign co-operative functions to 2,578 proteins, enabling systematic discovery of regulators of BAT. We also identify 638 proteins that correlate with protection from, or sensitivity to, at least one parameter of metabolic disease. We use these findings to uncover SFXN5, LETMD1, and ATP1A2 as modulators of BAT thermogenesis or adiposity, and provide OPABAT as a resource for understanding the conserved mechanisms of BAT regulation over metabolic physiology.
Assuntos
Tecido Adiposo Marrom , Proteoma , Humanos , Camundongos , Animais , Tecido Adiposo Marrom/metabolismo , Proteoma/metabolismo , Termogênese/fisiologia , Adiposidade , Obesidade/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas/metabolismoRESUMO
Chronic kidney disease (CKD) is more prevalent in individuals with obesity, diabetes mellitus, or hypertension. Individuals with CKD are prone to kidney failure, with symptom experiences that rival those of patients with cancer. We explored symptom burden in individuals with CKD via a systematic review of 30 quantitative and qualitative articles. The most common CKD symptoms were fatigue, weakness, pain, sleep disturbances and itchy skin. Instruments used to assess symptoms were the Kidney Disease Quality of Life (KDQOL)-36, the Palliative Outcome Symptom-Scale renal (POS-r)-13, and the Dialysis Symptom Index (DSI)-10. The included qualitative studies expand and expound on the quantitative data presented. This article describes the prevalence of symptom burden in individuals with CKD in relation to psychosocial and demographic factors and discuss the importance of symptom management.