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

Abstract

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.

Time-Restricted Feeding Restored Insulin-Growth Hormone Balance and Improved Substrate and Energy Metabolism in MC4RKO Obese Mice

“…In this experiment, TRF significantly increased the expression of WAT browning markers (UCP-1 and CIDEA) in the subcutaneous WAT. The expression change of WAT browning markers may contribute to improving the lipid and energy metabolism [37, 38]. Expression of target genes of GH and insulin (IGF-1, CD36, UCP1, PEPCK, PPARα, and SREBP1) [2] was significantly changed by TRF in liver and fat tissues.…”

The Rosmarinus Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes

“…Altogether, CA seems to control both adipogenesis and thermogenesis, and for the latter, it might be through tight control of thermogenic markers including the most important, UCP1. Under conditions where browning of white adipocytes is exacerbated, such as in critical illness after a severe burn injury or cachexia [8,[55][56][57], CA treatment may represent a potential therapeutic option. Animal models and patients with severe burns develop hypermetabolism with massive browning of white adipose tissue, hepatic steatosis, and cachexia, which are harmful and have limited therapeutic treatments.…”

“…Critical illnesses lead to more than 50% of deaths in the first week and may be due to sepsis, burns, or cancer-induced cachexia, which induce a negative energy balance with hyper-activation of BAT and high recruitment of new thermogenic adipocytes located within WAT, known as beige or brite adipocytes (brown-in-white) [8]. High increases in catecholamine production, such as epinephrine and norepinephrine, and pro-inflammatory factors are observed in critical illness, but pharmacologic treatments are associated with secondary effects such as gastrointestinal and cardiovascular failures.…”

Exploring the Role of Epicardial Adipose Tissue in Coronary Artery Disease From the Difference of Gene Expression

“…Its mitochondria express abundant uncoupling protein 1 (UCP1), and are rich in blood vessels and innervation. Cold and β3 receptor stimulation can trigger the yielding of UCP1-positive cells in WAT, which are similar in shape to BAT adipocytes, with multilocular lipid droplets and abundant mitochondria, and are named as “browning” adipocytes ( Alipoor et al, 2020 ; Reinisch et al, 2020 ). Under physiological conditions, Epicardial adipose tissue (EAT) belongs to WAT, but under pathological conditions, UCP1 expression increases in EAT which then presents “browning” changes ( Chechi et al, 2017 ).…”