Browning of Subcutaneous White Adipose Tissue in Humans After Severe Adrenergic Stress

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2015 Aug 6

PMID 26244931

Citations 193

Authors

Labros S Sidossis

Craig Porter

Manish K Saraf

Elisabet Borsheim

Ravi S Radhakrishnan

Tony Chao

Arham Ali

Maria Chondronikola

Ronald Mlcak

Celeste C Finnerty

Hal K Hawkins

Tracy Toliver-Kinsky

David N Herndon

Affiliations

Soon will be listed here.

Abstract

Since the presence of brown adipose tissue (BAT) was confirmed in adult humans, BAT has become a therapeutic target for obesity and insulin resistance. We examined whether human subcutaneous white adipose tissue (sWAT) can adopt a BAT-like phenotype using a clinical model of prolonged and severe adrenergic stress. sWAT samples were collected from severely burned and healthy individuals. A subset of burn victims were prospectively followed during their acute hospitalization. Browning of sWAT was determined by the presence of multilocular adipocytes, uncoupling protein 1 (UCP1), and increased mitochondrial density and respiratory capacity. Multilocular UCP1-positive adipocytes were found in sWAT samples from burn patients. UCP1 mRNA, mitochondrial density, and leak respiratory capacity in sWAT increased after burn trauma. Our data demonstrate that human sWAT can transform from an energy-storing to an energy-dissipating tissue, which opens new research avenues in our quest to prevent and treat obesity and its metabolic complications.

Citing Articles

Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men.

Nicolaisen T, Lyster A, Sjoberg K, Haas D, Voldstedlund C, Lundsgaard A Nat Metab. 2025; .

PMID: 40050437 DOI: 10.1038/s42255-025-01236-7.

Emerging debates and resolutions in brown adipose tissue research.

Cypess A, Cannon B, Nedergaard J, Kazak L, Chang D, Krakoff J Cell Metab. 2024; 37(1):12-33.

PMID: 39644896 PMC: 11710994. DOI: 10.1016/j.cmet.2024.11.002.

Hyperactive browning and hypermetabolism: potentially dangerous element in critical illness.

Huang L, Zhu L, Zhao Z, Jiang S Front Endocrinol (Lausanne). 2024; 15():1484524.

PMID: 39640882 PMC: 11617193. DOI: 10.3389/fendo.2024.1484524.

Two Regions with Different Expression of Lipogenic Enzymes in Rats' Posterior Subcutaneous Fat Depot.

Turyn J, Stelmanska E, Szrok-Jurga S Int J Mol Sci. 2024; 25(21).

PMID: 39519099 PMC: 11546078. DOI: 10.3390/ijms252111546.

Directly targeting PRDM16 in thermogenic adipose tissue to treat obesity and its related metabolic diseases.

Mao L, Lu J, Hou Y, Nie T Front Endocrinol (Lausanne). 2024; 15:1458848.

PMID: 39351529 PMC: 11439700. DOI: 10.3389/fendo.2024.1458848.

References

Zhang Q, Ma B, Fischman A, Tompkins R, Carter E . Increased uncoupling protein 1 mRNA expression in mice brown adipose tissue after burn injury. J Burn Care Res. 2008; 29(2):358-62. DOI: 10.1097/BCR.0b013e318166739c. View

Jeschke M, Chinkes D, Finnerty C, Kulp G, Suman O, Norbury W . Pathophysiologic response to severe burn injury. Ann Surg. 2008; 248(3):387-401. PMC: 3905467. DOI: 10.1097/SLA.0b013e3181856241. View

van Marken Lichtenbelt W, Vanhommerig J, Smulders N, Drossaerts J, Kemerink G, Bouvy N . Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009; 360(15):1500-8. DOI: 10.1056/NEJMoa0808718. View

Nedergaard J, Bengtsson T, Cannon B . Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007; 293(2):E444-52. DOI: 10.1152/ajpendo.00691.2006. View

WEIR J . New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949; 109(1-2):1-9. PMC: 1392602. DOI: 10.1113/jphysiol.1949.sp004363. View

Luft R, IKKOS D, Palmieri G, Ernster L, AFZELIUS B . A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control: a correlated clinical, biochemical, and morphological study. J Clin Invest. 1962; 41:1776-804. PMC: 291101. DOI: 10.1172/JCI104637. View

Yu Y, Tompkins R, Ryan C, Young V . The metabolic basis of the increase of the increase in energy expenditure in severely burned patients. JPEN J Parenter Enteral Nutr. 1999; 23(3):160-8. DOI: 10.1177/0148607199023003160. View

Gallagher D, Belmonte D, Deurenberg P, Wang Z, KRASNOW N, Pi-Sunyer F . Organ-tissue mass measurement allows modeling of REE and metabolically active tissue mass. Am J Physiol. 1998; 275(2):E249-58. DOI: 10.1152/ajpendo.1998.275.2.E249. View

Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Penicaud L . Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci. 1992; 103 ( Pt 4):931-42. DOI: 10.1242/jcs.103.4.931. View

10.

Young P, Arch J, Ashwell M . Brown adipose tissue in the parametrial fat pad of the mouse. FEBS Lett. 1984; 167(1):10-4. DOI: 10.1016/0014-5793(84)80822-4. View

11.

Wilmore D, Long J, MASON Jr A, Skreen R, PRUITT Jr B . Catecholamines: mediator of the hypermetabolic response to thermal injury. Ann Surg. 1974; 180(4):653-69. PMC: 1344163. DOI: 10.1097/00000658-197410000-00031. View

12.

Yang X, Enerback S, Smith U . Reduced expression of FOXC2 and brown adipogenic genes in human subjects with insulin resistance. Obes Res. 2003; 11(10):1182-91. DOI: 10.1038/oby.2003.163. View

13.

Porter C, Herndon D, Bhattarai N, Ogunbileje J, Szczesny B, Szabo C . Severe Burn Injury Induces Thermogenically Functional Mitochondria in Murine White Adipose Tissue. Shock. 2015; 44(3):258-64. PMC: 4537662. DOI: 10.1097/SHK.0000000000000410. View

14.

Gustafson B, Hammarstedt A, Hedjazifar S, M Hoffmann J, Svensson P, Grimsby J . BMP4 and BMP Antagonists Regulate Human White and Beige Adipogenesis. Diabetes. 2015; 64(5):1670-81. DOI: 10.2337/db14-1127. View

15.

Shinoda K, Luijten I, Hasegawa Y, Hong H, Sonne S, Kim M . Genetic and functional characterization of clonally derived adult human brown adipocytes. Nat Med. 2015; 21(4):389-94. PMC: 4427356. DOI: 10.1038/nm.3819. View

16.

Sidossis L, Kajimura S . Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. J Clin Invest. 2015; 125(2):478-86. PMC: 4319444. DOI: 10.1172/JCI78362. View

17.

Chondronikola M, Volpi E, Borsheim E, Porter C, Annamalai P, Enerback S . Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans. Diabetes. 2014; 63(12):4089-99. PMC: 4238005. DOI: 10.2337/db14-0746. View

18.

Porter C, Herndon D, Borsheim E, Chao T, Reidy P, Borack M . Uncoupled skeletal muscle mitochondria contribute to hypermetabolism in severely burned adults. Am J Physiol Endocrinol Metab. 2014; 307(5):E462-7. PMC: 4154069. DOI: 10.1152/ajpendo.00206.2014. View

19.

Lee P, Werner C, Kebebew E, Celi F . Functional thermogenic beige adipogenesis is inducible in human neck fat. Int J Obes (Lond). 2013; 38(2):170-6. PMC: 7034754. DOI: 10.1038/ijo.2013.82. View

20.

Shabalina I, Petrovic N, de Jong J, Kalinovich A, Cannon B, Nedergaard J . UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Rep. 2013; 5(5):1196-203. DOI: 10.1016/j.celrep.2013.10.044. View