@article{c77ced09641046c8a5e76522dad64090,
title = "A Thermogenic-like brown adipose tissue phenotype is dispensable for enhanced glucose tolerance in female mice",
abstract = "The prevailing dogma is that thermogenic brown adipose tissue (BAT) contributes to improvements in glucose homeostasis in obesogenic animal models, though much of the evidence supporting this premise is from thermostressed rodents. Determination of whether modulation of the BAT morphology/function drives changes in glucoregulation at thermoneutrality requires further investigation. We used loss- and gainof- function approaches including genetic manipulation of the lipolytic enzyme Pnpla2, change in environmental temperature, and lifestyle interventions to comprehensively test the premise that a thermogenic-like BAT phenotype is coupled with enhanced glucose tolerance in female mice. In contrast to this hypothesis, we found that 1) compared to mice living at thermoneutrality, enhanced activation of BAT and its thermogenic phenotype via chronic mild cold stress does not improve glucose tolerance in obese mice, 2) silencing of the Pnpla2 in interscapular BAT causes a brown-to-white phenotypic shift accompanied with inflammation but does not disrupt glucose tolerance in lean mice, and 3) exercise and low-fat diet improve glucose tolerance in obese mice but these effects do not track with a thermogenic BAT phenotype. Collectively, these findings indicate that a thermogenic-like BAT phenotype is not linked to heightened glucose tolerance in female mice.",
author = "Winn, {Nathan C.} and Rebeca Acin-Perez and Woodford, {Makenzie L.} and Hansen, {Sarah A.} and Haney, {Megan M.} and Ayedun, {Lolade A.} and Rector, {R. Scott} and Vieira-Potter, {Victoria J.} and Shirihai, {Orian S.} and Sacks, {Harold S.} and Kanaley, {Jill A.} and Jaume Padilla",
note = "Funding Information: Acknowledgments. The authors acknowledge the following University of Missouri core facilities for their expertise and contributions to this work: Molecular Cytology Core, Veterinary Diagnostic Medical Laboratory, and Charles W. Gehrke Proteomics Center. The authors thank Dr. Alexander Jurkevich and Dr. Frank Baker (Bond Life Sciences Center, University of Missouri, Columbia, MO) for their assistance with confocal microscopy and are thankful for the assistance of Jill Hansen and Dr. Cynthia Besch-Williford (IDEXX Laboratories, Inc.) for their help with immunohistochemistry. The technical assistance from Lisa Watkinson and Terry Carmack (Harry S. Truman Memorial Veterans{\textquoteright} Hospital, Columbia, MO) is greatly appreciated. Funding. This research was supported by the Cardiometabolic Disease Research Foundation (to J.P.) and Sears Trust Research Foundation (to J.P.). J.P. is supported by National Institutes of Health (NIH) grants R01-HL-137769 and K01-HL-125503. J.A.K. is supported by NIH grant R01-DK-101513. R.S.R. is supported by U.S. Department of Veterans Affairs VA-Merit Grant I01BX003271-01. N.C.W. is supported by NIH T32-DK-007563-31. L.A.A. was supported by Initiative for Maximizing Student Diversity EXPRESS Fellows Program R25GM056901. This work was supported in part with resources and the use of facilities at the Harry S. Truman Memorial Veterans{\textquoteright} Hospital. Publisher Copyright: {\textcopyright} 2019 by the American Diabetes Association.",
year = "2019",
month = sep,
day = "1",
doi = "10.2337/db18-1070",
language = "English",
volume = "68",
pages = "1717--1729",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "9",
}