Subcutaneous white adipose tissue independently regulates burn-induced hypermetabolism via immune-adipose crosstalk
Carly M. Knuth,
Dalia Barayan,
Ju Hee Lee,
Christopher Auger,
Lauar de Brito Monteiro,
Zachary Ricciuti,
Dea Metko,
Lisa Wells,
Hoon-Ki Sung,
Robert A. Screaton,
Marc G. Jeschke
Affiliations
Carly M. Knuth
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada
Dalia Barayan
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada
Ju Hee Lee
Translational Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4 Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
Christopher Auger
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
Lauar de Brito Monteiro
David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, ON L8L 2X2, Canada
Zachary Ricciuti
Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada
Dea Metko
Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada
Lisa Wells
Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada
Hoon-Ki Sung
Translational Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4 Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
Robert A. Screaton
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada
Marc G. Jeschke
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, ON L8L 2X2, Canada; Hamilton General Hospital, Hamilton Health Sciences, Hamilton, ON L8L 2X2, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; Corresponding author
Summary: Severe burns induce a chronic hypermetabolic state that persists well past wound closure, indicating that additional internal mechanisms must be involved. Adipose tissue is suggested to be a central regulator in perpetuating hypermetabolism, although this has not been directly tested. Here, we show that thermogenic adipose tissues are activated in parallel to increases in hypermetabolism independent of cold stress. Using an adipose tissue transplantation model, we discover that burn-derived subcutaneous white adipose tissue alone is sufficient to invoke a hypermetabolic response in a healthy recipient mouse. Concomitantly, transplantation of healthy adipose tissue alleviates metabolic dysfunction in a burn recipient. We further show that the nicotinic acetylcholine receptor signaling pathway may mediate an immune-adipose crosstalk to regulate adipose tissue remodeling post-injury. Targeting this pathway could lead to innovative therapeutic interventions to counteract hypermetabolic pathologies.
