White adipose tissue browning in critical illness: A review of the evidence, mechanisms and future perspectives.

Observational studies suggest better clinical outcomes following critical illness in patients with overweight and obesity (obesity paradox). An understanding of the morphologic, physiologic and metabolic changes in adipose tissue in critical illness may provide an explanation. Recent studies have demonstrated the transformation of white to brown-like adipocytes due to the "browning process," which has been of interest as a potential novel therapy in obesity during the last decade. The characteristics of the browning of white adipose tissue (WAT) include the appearance of smaller, multilocular adipocytes, increased UCP1 mRNA expression, mitochondrial density and respiratory capacity. These changes have been identified in some critical illnesses, which specifically refers to burns, sepsis and cancer cachexia in this study. The pathophysiological nature of WAT browning, underlying mechanisms, main regulators and potential benefits and harms of this process are interesting new areas that warrants further investigations. In this review, we discuss emerging scientific discipline of adipose tissue physiology in metabolic stress, available data, gaps of knowledge and future perspectives. Future investigations in this field may provide insights into the underlying mechanisms and clinical aspects of browning that may further our understanding of the proposed obesity paradox following critical illness, which may in turn open up opportunities for novel therapies to save lives and improve recovery.