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Sepsis Induces Adipose Tissue Browning in Nonobese Mice But Not in Obese Mice

Ayalon, Itay*; Shen, Hui*; Williamson, Lauren*; Stringer, Keith; Zingarelli, Basilia*; Kaplan, Jennifer M.*

doi: 10.1097/SHK.0000000000001076
Basic Science Aspects
Editor's Choice

ABSTRACT Severe sepsis and septic shock are the biggest cause of mortality in critically ill patients. Obesity today is one of the world's greatest health challenges. Little is known about the extent of involvement of the white adipose tissue (WAT) in sepsis and how it is being modified by obesity. We sought to explore the involvement of the WAT in sepsis. We hypothesize that sepsis induces browning of the WAT and that obesity alters the response of WAT to sepsis. Six-week-old C57BL/6 mice were randomized to a high-fat diet to induce obesity (obese group) or control diet (nonobese group). After 6 to 11 weeks of feeding, polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Mice were sacrificed at 0, 18, and 72 h after CLP and epididymal WAT (eWAT), inguinal WAT, and brown adipose tissue (BAT) harvested. Both types of WAT were processed for light microscopy and transmission electron microscopy to assess for morphological changes in both obese and nonobese mice. Tissues were processed for immunohistochemistry, image analyses, and molecular analyses. BATs were used as a positive control. Nonobese mice have an extensive breakdown of the unilocular lipid droplet and smaller adipocytes in WAT compared with obese mice after sepsis. Neutrophil infiltration increases in eWAT in nonobese mice after sepsis but not in obese mice. Nonobese septic mice have an increase in mitochondrial density compared with obese septic mice. Furthermore, nonobese septic mice have an increase in uncoupling protein-1 expression. Although the WAT of nonobese mice have multiple changes characteristic of browning during sepsis, these changes are markedly blunted in obesity.

*Division of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio

Division of Pathology and Laboratory Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio

Address reprint requests to Jennifer M. Kaplan, MD, MS, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2005, Cincinnati, OH 45229. E-mail: Jennifer.Kaplan@cchmc.org

Received 10 August, 2017

Revised 6 September, 2017

Accepted 30 November, 2017

NIH R01 GM126551 (JMK), R01 GM067202 (BZ), and P30DK078392.

The authors report no conflicts of interest.

© 2018 by the Shock Society