Cypess · The New England journal of medicine 2009 · retrospective cross-sectional cohort study · n=1972

Identification and importance of brown adipose tissue in adult humans.

Cited 4432 times in the scientific literature.

Level 3 - non-randomized controlled study

Retrospective cross-sectional observational cohort analysis with histological verification

PubMed 19357406 · doi:10.1056/NEJMoa0810780 · record verified 2026-08-27

What was done

The authors retrospectively analyzed 3,640 consecutive 18F-fluorodeoxyglucose (18F-FDG) PET-CT scans from 1,972 patients imaged for clinical diagnostic reasons to identify metabolically active brown adipose tissue (BAT) depots (defined as tissue >4 mm in diameter, adipose CT density, and maximal standardized 18F-FDG uptake >=2.0 g/mL). Clinical variables were compared with date-matched controls, and UCP1 immunostaining was performed on neck and supraclavicular surgical biopsy specimens.

What was found

Active BAT depots were identified from the anterior neck to thorax and confirmed via UCP1-immunopositive multilocular adipocytes on biopsy. Positive scans were detected in 7.5% of women (76/1,013) and 3.1% of men (30/959), indicating a female:male ratio >2:1 (P < 0.001); women also had greater BAT mass and FDG uptake activity. BAT detection probability was inversely correlated with age (P < 0.001), outdoor temperature at scan time (P = 0.02), beta-blocker use (P < 0.001), and body-mass index in older patients (P = 0.007).

Why it matters

This study demonstrates that adult humans possess functionally active, UCP1-expressing brown adipose tissue that correlates inversely with age, outdoor temperature, and BMI, establishing brown fat as a relevant factor in adult human metabolism.

Limits

The study relied on retrospective scans performed for clinical diagnostic indications rather than prospective cold-activation protocols, likely underestimating BAT prevalence. The cohort comprised clinical patients rather than a healthy population, and cross-sectional imaging data cannot determine causal metabolic relationships.

Cited by