Denis P. Blondin, 1 Sébastien M. Labbé, 2 Christophe Noll, 1 Margaret Kunach, 1 Serge Phoenix, 1,3 Brigitte Guérin, 3 Éric E. Turcotte, 3 François Haman, 4 Denis Richard, 2 and André C. Carpentier 1 Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes Diabetes 2015;64:2388–2397 | DOI: 10.2337/db14-1651 Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with 11 C-acetate, 18 F-fluoro-deoxyglucose ( 18 FDG), and 18 F-fluoro-thiaheptadecanoic acid ( 18 FTHA), a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesteri fied fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering. Despite smaller volumes of 18 FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative me- tabolism and NEFA uptake per BAT volume and an in- crease in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in 18 FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. 18 FDG-positive BAT volume and the cold-induced in- crease in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT “whitening.” The stimulation of the sympathetic nervous system resulting from cold exposure activates responses to defend against the cold (1). This includes the stimulation of brown adipose tissue (BAT), whose function is to pro- duce heat (2,3). The molecular signature of the largest and most prevalent BAT depot in adult humans, found in the supraclavicular region, also suggests that in contrast to the classical BAT found in rodents, human BAT consists of a mosaic of white and brown adipocytes (4). However, similar to rodents, it demonstrates remarkable plasticity based on chronic environmental conditions (5). In lean and healthy men, BAT can significantly contribute to cold-induced thermogenesis, fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TG) (6). In contrast, the volume of BAT positive for 18 F-fluoro-deoxyglucose ( 18 FDG), a positron-emitting glu- cose tracer (i.e., metabolically active BAT volume), and the clearance of circulating glucose by BAT are lower in cold- exposed overweight or obese individuals compared with lean individuals (7–9). BAT glucose clearance was also sig- nificantly lower in overweight or obese insulin-resistant individuals (7). Older age, higher BMI, and the pres- ence of type 2 diabetes are all independently associated with a lower prevalence of spontaneously activated BAT (10–12). BAT glucose uptake may not always reflect its thermogenic activity because glucose taken up by this tissue is used predominantly for de novo lipogenesis (13) and is highly dependent on intracellular TG content (5). Whether BAT thermogenesis is truly impaired in 1 Department of Medicine, Centre de Recherche du Centre hospitalier universitaire de Sherbrooke, Université de Sherbrooke, Quebec, Canada 2 Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Quebec, Canada 3 Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada 4 Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada Corresponding author: André C. Carpentier, denis.richard@criucpq.ulaval.ca. Received 28 October 2014 and accepted 5 February 2015. This article contains Supplementary Data online at http://diabetes .diabetesjournals.org/lookup/suppl/doi:10.2337/db14-1651/-/DC1. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. 2388 Diabetes Volume 64, July 2015 METABOLISM Downloaded from http://diabetesjournals.org/diabetes/article-pdf/64/7/2388/581408/db141651.pdf by guest on 21 October 2023