Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans
Additional Supporting Information may be found in the online version of this article.
Author Contributions: JO, PN, TN, KHP and KAV conceived and carried out the experiments and analyzed the data. RP, AR and SE conceived the experiments and interpreted the data. TV was responsible for the PET tracer production. All authors were involved in writing the paper and gave final approval of the submitted and published versions.
Disclosure: SE is a member of the scientific advisory board and shareholder of Ember Therapeutics. The authors declare no other duality of interest related to this manuscript.
Funding agencies: This study was conducted within the Finnish Center of Excellence in Molecular Imaging in Cardiovascular and Metabolic Research supported by the Academy of Finland, the University of Turku, the Hospital District of Southwest Finland, and Åbo Akademi University. The work was supported by grants from the Finnish Medical, Instrumentarium Science, Novo Nordisk, Paulo and Diabetes Research foundations, and Helsinki University Hospital Research Funds. The work was also supported by the European Union (EU FP7 project 278373; DIABAT), and grants from the Swedish Research Council (2009-2590 and 2010-3281), Sahlgrenska's University Hospital (LUA-ALF), the Knut and Alice Wallenberg and Söderberg foundations, and the Swedish Foundation for Strategic Research through the Center for Cardiovascular and Metabolic Research. SE thanks Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse for generous support, and all the authors acknowledge the staff of Turku PET Center and the Obesity Research Unit in Helsinki.
Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed.
Design and Methods
Using positron emission tomography (PET), cold- and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans were quantified. Further, cold-induced glucose uptake was measured in obese subjects before and after a 5-month conventional weight loss.
Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender.
The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.