Brown adipose tissue: therapeutic target in obesity treatment?

Methods to stimulate activation of brown tissue to promote weight loss and increase insulin sensitivity could result from this research.

The amount of brown adipose tissue in humans has been found to be inversely correlated with BMI, a finding that suggests this brown fat could play an important role in protecting against age-related obesity.

“These results are consistent with earlier reports showing a similar but not significant trend toward lower BMI in people with functionally active brown adipose tissue,” the researchers wrote in The New England Journal of Medicine.

“These observations are also consistent with murine studies showing that strains with higher levels of intermuscular brown adipose tissue are protected from diet-induced obesity and diabetes,” Aaron M. Cypess, MD, PhD, at Joslin Diabetes Center in Boston, and colleagues said.
Click here to listen to a clip of the interview with Dr. Cypess.

“We are hopeful that with increasing ability to measure the mass and activity of brown adipose tissue in humans in vivo, we will better understand its role in physiology and its potential as a therapeutic target in the treatment of obesity and other metabolic disorders.”

F-FDG PET-CT quantified fat

Investigators used 3,640 consecutive F-fluorodeoxyglucose PET and CT scans of 1,972 patients from August 2003 through May 2006 to ascertain the presence of the brown adipose tissue.

Substantial depots of the fat were defined as collections of tissue that measured >4 mm in diameter, had CT-identified density of adipose tissue, and had a maximal standardized uptake value of F-FDG ≥2.0 g/mL, indicating high metabolic activity, according to the researchers.

“We are very excited about our findings and those of the other groups which demonstrate clearly that adult humans have brown fat,” C. Ronald Kahn, MD, professor at Joslin Diabetes Center and Harvard Medical School, told Endocrine Today.

“More interestingly, there appears to be more, or at least more active, brown fat in lean, young individuals than older, obese individuals; this suggests that having more brown fat may protect against obesity,” he said.

Brown tissue found in adults

Brown adipose tissue was identified in 7.5% of the women and 3.1% of the men. In the cervical, supraclavicular and superior mediastinal depots, the median amount of brown tissue was 12.3 g in women and 11.6 g in men. Findings suggested that the capacity to increase the mass and activity of brown tissue was greater in women than in men. The cervical-supraclavicular depot was the most common location for brown tissue.

Brown tissue was detected most in patients aged younger than 50 years (P<.001), the least obese patients (P=.04), patients with the lowest fasting plasma glucose levels (P=.04), patients not using beta-blockers (P<.001) and patients who had never smoked (P=.02).

“Looking to the future, we hope to find ways to stimulate the amount or activity of brown fat for the prevention and treatment of obesity and obesity-related diseases like type 2 diabetes. We think this will be possible and, in fact, are working in rodents to determine what factors might work to achieve this goal,” Kahn said. – by Christen Haigh

Cypess AM. N Engl JMed. 2009;360:1509-1517.

The authors should be commended for their resourcefulness in correlating CT-derived fat density with unusually high ¹⁸ F-fluorodeoxyglucose uptake on PET in over 1,900 patients and putting the two findings together as evidence for the existence of brown adipose tissue in humans. In this study, the authors identified the most common site of purported brown fat in the subcutaneous tissue of the neck and supraclavicular space. Furthermore, they identified a strong negative correlation between the presence of brown fat and the presence of several components of the cardiometabolic syndrome, notably including more severe obesity. An important consideration in interpreting and extrapolating from the findings of this study is that the CT/PET scan findings interpreted as suggestive of brown fat were only identified in slightly more than 5% of the patients studied. We should look with great interest for further human studies of brown adipose tissue.

– Stephen A. Brietzke, MD

Endocrine Today Editorial Board member