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. 2014 Dec;63(12):4089-99.
doi: 10.2337/db14-0746. Epub 2014 Jul 23.

Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans

Maria Chondronikola  1 , Elena Volpi  2 , Elisabet Børsheim  3 , Craig Porter  3 , Palam Annamalai  4 , Sven Enerbäck  5 , Martin E Lidell  5 , Manish K Saraf  3 , Sebastien M Labbe  6 , Nicholas M Hurren  3 , Christina Yfanti  7 , Tony Chao  8 , Clark R Andersen  3 , Fernando Cesani  9 , Hal Hawkins  10 , Labros S Sidossis  11
Affiliations

Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans

Maria Chondronikola et al. Diabetes. 2014 Dec.

Abstract

Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT(+) group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.

Trial registration: ClinicalTrials.gov NCT01791114.

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Figures

Figure 1
Figure 1
Study design. The following tracers infused: [6,6-2H2]-glucose, [U-13C16] palmitate, and 13C sodium bicarbonate. IC, indirect calorimetry.
Figure 2
Figure 2
The role of BAT in REE and substrate oxidation. A: REE upon CE and TN conditions in BAT+ subjects and BAT− subjects. B: Plasma glucose oxidation under CE and TN conditions in BAT+ and BAT− subjects. C: Plasma FFA oxidation under CE and TN conditions in BAT+ and BAT− subjects. White bars, TN; black bars, CE. Data are mean ± SEM. *P < 0.05, CE vs. TN.
Figure 3
Figure 3
Mean SUV for glucose of various tissues during CE and TN conditions. SQAT, subcutaneous adipose tissue; VAT, visceral adipose tissue; white bars, TN; black bars, CE. Data are mean ± SEM. *P < 0.05, **P < 0.01, CE vs. TN.
Figure 4
Figure 4
Effect of BAT on whole-body glucose disposal and insulin sensitivity. Change in whole-body glucose disposal under CE relative to TN in basal condition (A) and during hyperinsulinemic-euglycemic clamp (B). C: Change in the insulin sensitivity index (ISI) for CE and TN. D: Change in whole-body insulin sensitivity for CE relative to TN. Data are means ± SEM. White bars, BAT−; black bars, BAT+. *P < 0.05 and **P < 0.01, significant change with CE vs. TN conditions. †P < 0.05, BAT+ vs. BAT−.
Figure 5
Figure 5
Change in plasma concentrations of hormones and cytokines with CE in BAT+ and BAT− subjects. A: Change in plasma norepinephrine levels with CE in BAT+ and BAT− individuals. B: Change in plasma FGF21 concentrations with CE in BAT+ and BAT− individuals. Change in plasma FT3 (C) and plasma FT4 (D) concentrations with CE in BAT+ and BAT− individuals. E: Change in plasma irisin concentration with CE in BAT+ and BAT− individuals. F: Change in serum IL-6 concentrations with CE in BAT+ and BAT− individuals. Data are mean ± SEM. *P < 0.05 and **P < 0.01, significant difference in response to CE between BAT+ and BAT− subjects.
Figure 6
Figure 6
Molecular and functional characterization of supraclavicular and abdominal subcutaneous adipose tissue samples in BAT+ and BAT− subjects under conditions of cold-induced BAT. UCP1 staining (×40) in the supraclavicular (A and B) and abdominal (ABD) subcutaneous (C and D) adipose tissue samples from representative BAT+ (A and C) and BAT− (B and D) participants. E: Quantification of UCP1 staining in supraclavicular (SC) and ABD subcutaneous adipose tissue. F: UCP1 gene expression in SC and ABD subcutaneous adipose tissue. G: Uncoupled mitochondrial respiration in SC and ABD subcutaneous adipose tissue. Data are mean ± SEM. White circles, BAT−; black circles, BAT+. *P < 0.05. H: UCP1 gene expression in BAT under TN and CE conditions. Data are mean ± SD. ***P < 0.005. I: DIO2 gene expression in BAT under TN and CE conditions. Data are mean ± SD. ***P < 0.005.
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References

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