Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published February 23, 2022


Could long-term activation of brown adipose tissue help to treat obesity?

Fat is not one entity; it is a collection of related but different anatomical and functional adipose-tissue depots. Read the NEJM Review Article here.

Clinical Pearls

Q: What is the primary function of white adipose tissue (WAT)?

A: The primary function of WAT is to store energy in the form of triglycerides, yet there are substantial, clinically relevant physiological differences among the various WAT depots. Metabolic health risks are therefore due at least as much to the location of excess triglyceride storage as to the overall fat mass of the body.

Q: Where are depots of brown adipose tissue (BAT) located in adults?

A: Brown adipose tissue (BAT) consumes glucose and triglycerides, generating heat. Once thought to be physiologically irrelevant in adult humans, long-term activation of BAT has been hypothesized to contribute to wide-ranging health benefits in tissues as diverse as the gastrointestinal, cardiovascular, and musculoskeletal systems. Adult human BAT is found only in certain anatomical depots in the neck, shoulders, posterior thorax, and abdomen.

Morning Report Questions 

Q: What are some of the more recently understood functions of adipose tissue in humans?

A: WAT has three commonly understood and related macroscopic functions. It stores food calories, creates a layer of thermal insulation, and provides mechanical protection, which is important for resisting infection and injury. Insulin is the principal driver of fuel absorption and storage, with adipose tissue responsible for 5% of insulin-mediated glucose uptake in adults who are lean and 20% in those who are obese. Until three decades ago, these physiological roles were all that most people considered when thinking about WAT, but the discoveries of white adipocyte–derived hormones such as leptin and adiponectin made clear that WAT is also an endocrine organ. WAT and, more recently, BAT have been identified as integral and regulatable components of lipoprotein and bile acid metabolism. More than a decade after the discovery of BAT as a functional tissue in adult humans, there is nascent evidence suggesting that BAT activation may lower the risk of atherosclerosis and drive the consumption of glucose and lipids by skeletal muscle. Both WAT and BAT participate in immunomodulation, the suppression and activation of the immune system, and each tissue releases its distinct profile of mediators of the complement system.

Q: Could long-term activation of BAT help to treat obesity?

A: In rodents, the answer is unequivocally yes, but in humans, the answer has yet to be determined. Humans have proportionally less BAT than smaller mammals, but contemporary humans may have even less BAT than is required to support their physiological and metabolic needs. BAT mass dramatically decreases with increased ambient temperatures, and aging also appears to induce BAT atrophy, raising the possibility that contemporary humans who create a thermoneutral environment are artificially lowering their BAT mass and its contribution to energy balance and metabolic health. Even the limited BAT present in adults appears to have a substantial clinical effect, because retrospective and prospective studies show an inverse association between BAT activity and BMI. In addition, a recent study showed that persons with BAT had healthier blood glucose, triglyceride, and high-density lipoprotein levels than persons without BAT. Those with BAT had a lower prevalence of cardiometabolic diseases such as type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure, and hypertension. Clinical trials are necessary to determine the outcomes from long-term BAT activation, given that studies in rodents suggest that activating BAT could lead to compensatory food intake or the opposite, suppression of appetite.

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