Abstract
Obesity is endemic in many regions of the world and a forerunner of several serious and sometimes fatal diseases such as ischemic heart disease, stroke, kidney failure and neoplasia. Although we know its origin—it results when energy intake exceeds energy expenditure—at present, the only proven therapy is bariatric surgery. This is a major abdominal procedure that, for reasons that are largely unknown (it cannot be explained solely by a reduction in ventricular volume), significantly reduces energy intake, but because of cost and limited availability, it will most likely be reserved for only a small fraction of those who stand to gain from effective antiobesity treatment. Clearly, alternative ways to treat obesity are needed. Another way to combat excessive accumulation of white adipose tissue would be to increase energy expenditure. Rodents, hibernators and human infants all have a specialized tissue—brown adipose tissue (BAT)—with the unique capacity to regulate energy expenditure by a process called adaptive thermogenesis. This process depends on the expression of uncoupling protein-1 (UCP1), which is a unique marker for BAT. UCP1 is an inner mitochondrial membrane protein that short circuits the mitochondrial proton gradient, so that oxygen consumption is no longer coupled to adenosine triphosphate synthesis. As a consequence, heat is generated. Mice lacking ucp-1 are severely compromised in their ability to maintain normal body temperature when acutely exposed to cold and they are also prone to become obese. We have shown that, in mice, BAT protects against diet-induced obesity, insulin resistance and type 2 diabetes. This is based on prevention of excessive accumulation of triglyceride in non-adipose tissues such as muscle and liver. Ectopic triglyceride storage at these locations is associated with initiation of insulin resistance and, ultimately, development of type 2 diabetes.
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Acknowledgements
I apologize to all colleagues who have been cited only cursorily, or have not been cited because of space constraints. This work was supported by generous grants from the Söderberg Foundation, the Swedish Research Council (Grant K2005-32BI-15324-01A), the Arne and IngaBritt Lundberg Foundation, the Knut and Alice Wallenberg Foundation and the Swedish Foundation for Strategic Research through the Center for Cardiovascular and Metabolic Research.
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Enerbäck, S. Brown adipose tissue in humans. Int J Obes 34 (Suppl 1), S43–S46 (2010). https://doi.org/10.1038/ijo.2010.183
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