A Thermogenic-like brown adipose tissue phenotype is dispensable for enhanced glucose tolerance in female mice

Nathan C. Winn, Rebeca Acin-Perez, Makenzie L. Woodford, Sarah A. Hansen, Megan M. Haney, Lolade A. Ayedun, R. Scott Rector, Victoria J. Vieira-Potter, Orian S. Shirihai, Harold S. Sacks, Jill A. Kanaley, Jaume Padilla

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Pages (from-to)1717-1729
Number of pages13
JournalDiabetes
Volume68
Issue number9
DOIs
StatePublished - 1 Sep 2019
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint

Dive into the research topics of 'A Thermogenic-like brown adipose tissue phenotype is dispensable for enhanced glucose tolerance in female mice'. Together they form a unique fingerprint.

Cite this