Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans

Abstract

Brown adipose tissue (BAT) is vital for proper thermogenesis during cold exposure in rodents, but until recently its presence in adult humans and its contribution to human metabolism were thought to be minimal or insignificant. Recent studies using PET with 18 F-fluorodeoxyglucose ( 18 FDG) have shown the presence of BAT in adult humans. However, whether BAT contributes to cold-induced nonshivering thermogenesis in humans has not been proven. Using PET with 11 C-acetate, 18 FDG, and 18 F-fluoro-thiaheptadecanoic acid ( 18 FTHA), a fatty acid tracer, we have quantified BAT oxidative metabolism and glucose and nonesterified fatty acid (NEFA) turnover in 6 healthy men under controlled cold exposure conditions. All subjects displayed substantial NEFA and glucose uptake upon cold exposure. Furthermore, we demonstrated cold-induced activation of oxidative metabolism in BAT, but not in adjoining skeletal muscles and subcutaneous adipose tissue. This activation was associated with an increase in total energy expenditure. We found an inverse relationship between BAT activity and shivering. We also observed an increase in BAT radio density upon cold exposure, indicating reduced BAT triglyceride content. In sum, our study provides evidence that BAT acts as a nonshivering thermogenesis effector in humans.

Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans

“…Because glucose is not the primary substrate, BAT activity based on [ 18 F]FDG uptake may underestimate and potentially miss components of BAT energy metabolism under certain physiological conditions. While [ 18 F]FDG-PET-based assessments of human BAT activity in response to acute [20,21,38,42] and chronic [2,4] cold exposure have reflected the expected outcomes based on rodent experiments, this study indicates that there are species differences for other adaptive stimuli. Although we have shown that pioglitazone reduced coldstimulated BAT glucose uptake, we cannot definitively claim that fat oxidative capacity also decreased.…”

“…Although we have shown that pioglitazone reduced coldstimulated BAT glucose uptake, we cannot definitively claim that fat oxidative capacity also decreased. Nevertheless, previous acute cold interventions in similar participants resulted in parallel kinetics between fatty acid and glucose PET tracers [42], thus it is likely that our findings are relevant for BAT thermogenic activity. Our study design minimised the impact of individual and non-BAT [ 18 F]FDG uptake variability by conducting pre-and post-imaging on all participants, tightly controlling laboratory conditions and maximising statistical and experimental rigor by including a placebo-treated group.…”

Exercise regulation of adipose tissue

“…BAT oxidative metabolism has been shown to be a significant contributor to whole body energy expenditure. 9,10 The relatively recent "re-discovery" of BAT in adult humans and its known role in adaptive thermogenesis has made activation of this tissue a prominent focus of metabolic research. The amount of BAT in humans has been shown to vary with age, BMI, and gender, compounding the complexity of these studies.…”

Brown Adipose Tissue in Humans

“…PET is a highly sensitive and specific imaging tool for studies of BAT physiology (Table 1). (Orava et al 2011, Muzik et al 2012 [ (Virtanen et al 2009, Orava et al 2011 Free fatty acid metabolism (Ouellet et al 2012) [ 18 F]FTHA 109…”

“…The images were corrected for the T2*--decay effect by fitting T2*--decay parameters for fat and water signals respectively using a model similar to that described by O'Regan et al (2008).…”