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Publication : KLF15 controls brown adipose tissue transcriptional flexibility and metabolism in response to various energetic demands.

First Author  Fan L Year  2022
Journal  iScience Volume  25
Issue  11 Pages  105292
PubMed ID  36304102 Mgi Jnum  J:335121
Mgi Id  MGI:7379920 Doi  10.1016/j.isci.2022.105292
Citation  Fan L, et al. (2022) KLF15 controls brown adipose tissue transcriptional flexibility and metabolism in response to various energetic demands. iScience 25(11):105292
abstractText  Brown adipose tissue (BAT) is a specialized metabolic organ responsible for non-shivering thermogenesis. Recently, its activity has been shown to be critical in systemic metabolic health through its utilization and consumption of macronutrients. In the face of energetically demanding states, metabolic flexibility and systemic coordination of nutrient partitioning is requisite for health and survival. In this study, we elucidate BAT's differential transcriptional adaptations in response to multiple nutrient challenges and demonstrate its context-dependent prioritization of lipid, glucose, and amino acid metabolism. We show that the transcription factor Kruppel-like factor 15 (KLF15) plays a critical role in BAT metabolic flexibility. BAT-specific loss of KLF15 results in widespread changes in circulating metabolites and severely compromised thermogenesis in response to high energy demands, indicative of impaired nutrient utilization and metabolic flexibility. Together, our data demonstrate KLF15 in BAT plays an indispensable role in partitioning resources to maintain homeostasis and ensure survival.
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