Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2016 Jun 14;23(6):1200-1206.
doi: 10.1016/j.cmet.2016.04.029. Epub 2016 May 26.

Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans

Maria Chondronikola  1 , Elena Volpi  2 , Elisabet Børsheim  3 , Craig Porter  3 , Manish K Saraf  3 , Palam Annamalai  4 , Christina Yfanti  5 , Tony Chao  6 , Daniel Wong  7 , Kosaku Shinoda  7 , Sebastien M Labbė  8 , Nicholas M Hurren  3 , Fernardo Cesani  9 , Shingo Kajimura  7 , Labros S Sidossis  10
Affiliations
Clinical Trial

Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans

Maria Chondronikola et al. Cell Metab. .

Abstract

Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Brown Adipose Tissue Activation and Lipid Kinetics
(A) Mean standardized disposal value (SUV) for 2-Deoxy-2-[18F]fluoroglucose glucose of various tissues during cold exposure (CE) and thermoneutral (TN) conditions (n = 13–16). SQAT, subcutaneous adipose tissue; VAT, visceral adipose tissue. Data presented are mean and SD. **p = 0.003 using Wilcoxon’s matched pairs signed rank test. (B) Mean radiodensity of various tissues during CE and TN conditions (n = 13–16). SQAT, subcutaneous adipose tissue; VAT, visceral adipose tissue. Data presented are mean and SD. *p = 0.01 using Wilcoxon’s matched pairs signed rank test. (C) Correlation of BAT volume with the cold-induced change in whole-body free fatty acid (FFA) oxidation. Indirect calorimetry was completed in 14 participants. The dashed lines represent 95% confidence intervals. p = 0.005 using Pearson’s r. (D and E) Correlation of BAT volume with the cold-induced change in the whole-body lipolysis rate presented as FFA rate of appearance (Ra) (D) and glycerol Ra (n = 16) (E). The dashed lines represent 95% confidence intervals. p = 0.008 for FFA Ra and p = 0.03 for glycerol Ra using Pearson’s r. (F) Correlation of BAT volume with the cold-induced change in total triglyceride (TG)-FFA cycling (n = 14). Indirect calorimetry was completed in 14 participants. The dashed lines represent 95% confidence intervals. p = 0.01 using Pearson’s r. (G) Correlation of BAT volume with the cold-induced change in adipose tissue insulin sensitivity (estimated as percent suppression in Ra [Palm Ra] with insulin). The insulin clamp procedure was completed in 13 participants. The dashed lines represent 95% confidence intervals. p = 0.01 using Pearson’s r. See also Tables S1–S3 and Figure S1.
Figure 2
Figure 2. Functional and Molecular Analysis of Supraclavicular and Abdominal Subcutaneous Adipose Tissue Samples
(A) Oxygen consumption rates in supraclavicular brown adipose tissue (BAT) (n = 4) and subcutaneous abdominal (n = 4) adipose tissue samples from the same participants, collected during cold exposure (CE). Supraclavicular samples with significant amounts of uncoupling protein 1 (UCP1)-positive adipocytes were determined by the suppression of leak respiration upon addition of purine nucleotides. Leak respiration (basal) with sample alone is reported followed by leak respiration with complex I substrates but no ADP (State 2), followed by phosphorylating respiration with complex I substrates and saturating (5 mM) ADP (State 3). Data presented are means and SD; *p < 0.05 using Student’s t test. (B) Respiratory control ratio (State 3 to State 2 respiration) was calculated as an index of uncoupled mitochondria in supraclavicular BAT (n = 4) and abdominal subcutaneous (n = 4) adipose tissue samples. Data are means and SD. **p = 0.001 using Student’s t test. (C and D) Relative mRNA expression in supraclavicular (n = 8) (C) and subcutaneous abdominal adipose tissue (n = 8) (D) of uncoupling protein 1 (UCP1) and genes regulating lipid metabolism in BAT lipoprotein lipase (LPL), and cluster of differentiation 36 (CD36) in CE and thermoneutral (TN) conditions. *p = 0.02 and **p = 0.008 by Wilcoxon rank test. (E) Expression profiles of genes involved in fatty acid/lipid metabolism in the BAT and WAT depots from Subject 2 during CE and TN conditions. The color scale shows z-scored fragments per kilobase of transcript per million mapped reads representing the mRNA level of each gene in blue-white-red scheme (blue, low expression; red, high expression). HMGCS2, 3-hydroxy-3-methylglutaryl-CoA synthase 2; ACADVL1, acyl-CoA dehydrogenase very long chain; ECHS1, enoyl CoA hydratase short chain 1; DGAT1/2, diacylglycerol acyltransferase 1 and 2; SLC25A20, solute carrier family 25 carnitine/acylcarnitine translocase member 20; HADHB, hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/rnoyl-CoA hydratase beta subunit; ECI1, enoyl-CoA delta isomerase 1; CPT1B, carnitine-palmitoyltransferase 1B; AGPAT3, 1-acylglycerol-3-phosphate O-acyltransferase 3; PPARA, peroxisome proliferator-activated receptor alpha; ACLY, ATP citrate lyase; DECR1, 2,4-dienoyl CoA reductase 1; GK, glycerol kinase; ACADM, acyl-CoA dehydrogenase C-4 to C-12 straight chain; BDH1, 3-hydroxybutyrate dehydrogenase type 1; DLD, dihydrolipoamide dehydrogenase; ACAA2, acetyl-CoA acyltransferase 2. See also Figure S2.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H, Waurisch C, et al. Brown adipose tissue activity controls triglyceride clearance. Nat. Med. 2011;17:200–205. - PubMed
    1. Bartness TJ, Shrestha YB, Vaughan CH, Schwartz GJ, Song CK. Sensory and sympathetic nervous system control of white adipose tissue lipolysis. Mol. Cell. Endocrinol. 2010;318:34–43. - PMC - PubMed
    1. Berbée JF, Boon MR, Khedoe PP, Bartelt A, Schlein C, Worthmann A, Kooijman S, Hoeke G, Mol IM, John C, et al. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development. Nat. Commun. 2015;6:6356. - PMC - PubMed
    1. Blondin DP, Labbé SM, Tingelstad HC, Noll C, Kunach M, Phoenix S, Guérin B, Turcotte EE, Carpentier AC, Richard D, Haman F. Increased brown adipose tissue oxidative capacity in cold-acclimated humans. J. Clin. Endocrinol. Metab. 2014;99:E438–E446. - PMC - PubMed
    1. Blondin DP, Labbé SM, Phoenix S, Guérin B, Turcotte EE, Richard D, Carpentier AC, Haman F. Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men. J. Physiol. 2015;593:701–714. - PMC - PubMed

Publication types

-