The effects of temperature and seasons on subcutaneous white adipose tissue in humans: Evidence for thermogenic gene induction

Two kinds of fat tissue are present in mammals: white adipose fat (WAT) and brown adipose fat (BAT). Exposure to a cold environment in the winter activates BAT, which defends against the cold by releasing energy as heat. Increased energy expenditure associated with BAT activation has been shown to prevent obesity in rodents. There is an inverse relationship between activation of BAT and adiposity, and elevated inflammation is associated with increased WAT depots. In addition to BAT activation, the thermogenic capacity of rodents can be increased by browning, a process in which some WAT depots are converted to beige fat (mixture of brown and white fat). As with BAT activation, browning appears to be a defense against cold and obesity. Both browning and BAT activation increase expression of a mitochondrial protein called UCP1 that uncouples oxidative respiration to generate heat. Another protein called PGC1α appears to act synergistically with UDP1 to activate brown fat in a cold environment. Preliminary data suggest that brown fat may also be a defense against cold and obesity in humans, but it is unclear whether adult humans exposed to the cold have the ability to transform some white fat deposits into beige fat. The aim of this study was to investigate the capability of WAT from human fat depots to respond to seasonal cold exposure with increased markers of beige fat. In addition, the role of obesity and inflammation in the process of browning in humans was investigated. Both abdominal and thigh subcutaneous (SC)WAT depots biopsied from 56 subjects in the summer or winter were examined, and the effects of an acute cold stimulus on adipose gene expression was assessed after application of a cold pack (stimulus) to the thigh of 16 physically active young subjects. Real-time reverse transcriptase-polymerase chain reaction was used to assess gene expression in adipose tissue biopsies, and Western blottingwas performed tomeasure protein levels of UCP1. Expression of both UCP1 and PGC1α mRNA was higher in the winter than the summer in abdominal SC WAT (4- to 10-fold [P < 0.05] and 1.5- to 2-fold higher, respectively) as was beige adipose markers, and the level of UCP1 protein was 3-fold higher in the winter. The seasonal induction of abdominal SCWAT UCP1 mRNA was substantially diminished in obese subjects (body mass index ( [BMI] >30 kg/m²). Application of an acute cold stimulus to the thigh of subjects for 30 minutes increased expression of UCP1 and PGC1α mRNA by 1.9-fold (P < 0.07) and 2.7-fold (P < 0.015), respectively. Exposure of human adipocytes in culture to acute cold in conditioned medium induced a 2- to 3-fold increase in expression of PGC1α and UCP1 mRNA; this effect in cold-treated cells was inhibited by conditioned medium from macrophages and by the addition of tumor necrosis factor α. These data show that human SC WAT increases expression of thermogenic genes seasonally and acutely in response to a cold stimulus. This response is inhibited by obesity and inflammation. Browning of WAT in humans has the potential to defend against obesity by burning extra calories rather than converting them into additional fat tissue.