Cold Induced Changed in Human Subcutaneous White Adipose

The recent rediscovery of human brown adipose tissue through PET-CT has initiated more research on thermogenesis and provocative questions about adipose browning as a defense against obesity. Although functional brown adipose tissue (BAT) can be demonstrated in humans, a question remains regarding the functional relevance of the relatively small BAT depots that are deep within the human body cavity. On the other hand, many studies have demonstrated that white adipose tissue (WAT) in mice has the ability to upregulate its thermogenic capacity and become “beige”. No studies have demonstrated browning of typical human WAT depots, except for our recent studies. We have recently examined the subcutaneous (SC) WAT of humans and found a considerable ability to upregulate UCP1 and other mitochondrial genes in response to cold and to seasons, and we have demonstrated this phenomenon with human adipocytes in culture. The seasonal changes in WAT are of particular interest, since this indicates a physiologic response to colder weather even in a modern society, without provocative and unphysiologic experimental conditions. In addition, we found that obese humans with a high SC WAT macrophage burden do not upregulate SC WAT UCP1 as well, suggesting that adipose inflammation inhibits the increased thermogenic capacity of WAT. A number of immune-mediate functions are involved in this process. Based on these data, we propose the following hypotheses. Hypothesis 1. Cold temperatures will induce changes in human subcutaneous white adipose tissue (WAT) consistent with beiging and immune mediators are involved. Hypothesis 2. This WAT browning effect can be demonstrated acutely, in response to seasons, and can be inhibited by â-blockers. Hypothesis 3. Obese insulin resistant subjects are resistant to cold induced changes due to the inflammatory milieu of WAT. Hypothesis 4. Cold- and season-induced changes in WAT will lead to functional changes, characterized by increased mitochondrial uncoupling and increased resting metabolic rate.