Abstract
Obesity-associated metabolic abnormalities comprise a cluster of conditions including dyslipidemia, insulin resistance, diabetes and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from the accumulation of white adipose tissues mainly due to the chronic imbalance of energy intake and energy expenditure. A variety of approaches to treat or prevent obesity, including lifestyle interventions, surgical weight loss procedures and pharmacological approaches to reduce energy intake and increase energy expenditure have failed to substantially decrease the prevalence of obesity. Brown adipose tissue (BAT), the primary source of thermogenesis in infants and small mammals may represent a promising therapeutic target to treat obesity by promoting energy expenditure through non-shivering thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1). Since the confirmation of functional BAT in adult humans by several groups, approximately a decade ago, and its association with a favorable metabolic phenotype, intense interest on the significance of BAT in adult human physiology and metabolic health has emerged within the scientific community to explore its therapeutic potential for the treatment of obesity and metabolic diseases. A substantially decreased BAT activity in individuals with obesity indicates a role for BAT in the setting of human obesity. On the other hand, BAT mass and its prevalence correlate with lower body mass index (BMI), decreased age and lower glucose levels, leading to a lower incidence of cardio-metabolic diseases. The increased cold exposure in adult humans with undetectable BAT was associated with decreased body fat mass and increased insulin sensitivity. A deeper understanding of the role of BAT in human metabolic health and its interrelationship with body fat distribution and deciphering proper strategies to increase energy expenditure, by either increasing functional BAT mass or inducing white adipose browning, holds the promise for possible therapeutic avenues for the treatment of obesity and associated metabolic disorders.
Highlights
The prevalence of obesity and related metabolic complications have significantly increased worldwide
Since obesity mainly develops from surplus energy stored in the adipose tissues, therapeutic strategies directed against increasing the energy expenditure and reducing the energy intake, or both, provide attractive avenues to combat obesity-associated metabolic complications
In obese humans, visceral white adipose tissues (WAT) show a higher expression of uncoupling protein 1 (UCP1) and several other adipose browning (CIDEA, PRDM16, TBX1 and P2RX5) and mitochondrial (COX8B, PGC1α, ATP5A and NDUFA1) genes compared to the subcutaneous adipose depots [88]
Summary
The prevalence of obesity and related metabolic complications have significantly increased worldwide. BAT, by virtue of its ability to modulate the organism’s global energy expenditure in the form of heat, has been a subject of tremendous interest to counteract obesity-related diseases. Besides the wellaccepted view that BAT activation is beneficial in general, results of unfavorable outcomes from the hyper-activation of BAT have been reported in promoting atherosclerosis in animal models [19], cancer cachexia [20] and breast cancer cells in promoting cancer progression [21] These findings suggest, that therapeutic interventions for the treatment of obesity-associated metabolic conditions using BAT activation should be carefully controlled and monitored
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