CD137 negatively affects “browning” of white adipose tissue during cold exposure

Abstract

<jats:p>Prolonged cold exposure stimulates the formation of brownlike adipocytes expressing UCP1 (uncoupling-protein-1) in subcutaneous white adipose tissue which, together with classical brown adipose tissue, contributes to maintaining body temperature in mammals through nonshivering thermogenesis. The mechanisms that regulate the formation of these cells, alternatively called beige or brite adipocytes, are incompletely understood. Here we report that mice lacking CD137, a cell surface protein used in several studies as a marker for beige adipocytes, showed elevated levels of thermogenic markers, including UCP1, increased numbers of beige adipocyte precursors, and expanded UCP1-expressing cell clusters in inguinal white adipose tissue after chronic cold exposure. CD137 knockout mice also showed enhanced cold resistance. These results indicate that CD137 functions as a negative regulator of “browning” in white adipose tissue and call into question the use of this protein as a functional marker for beige adipocytes.</jats:p>

Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice

“…However, there were several clones that revealed a surprising dissociation of expression between these markers for brown adipocytes. The beige adipocyte markers Cd137 and Tmem26 were not expressed in the same pattern, with highest expression of these genes in different non-overlapping cell lines, which is in line with a recent report describing CD137 as a negative regulator of beige adipocyte function (37). Moreover, RT-qPCR analysis for Adiponectin, Cd36, Fabp4, Glut4, and Hsl from 64 out of the 67 cell clones (not including three cell lines with lowest differentiation capacity: 2D5, 3A9, and 3A10) revealed heterogeneity in general adipocyte marker gene expression ( Fig S2B).…”

Sustained anti‐obesity effects of life‐style change and anti‐inflammatory interventions after conditional inactivation of the activin receptor ALK7

“…For immunoblotting analysis, proteins were precipitated from the organic phase obtained with the TRIzol reagent (see above) as previously described. 23 Protein pellets were dissolved in sample buffer, supplemented with β-mercaptoethanol and heated at 95℃ for 10 minutes. The samples were centrifuged at 10 000 rpm for 10 minutes to remove particulates, and protein content was estimated using Pierce 660nm protein assay reagent (Thermo Fisher Scientific, Cat no.…”

Sustained anti-obesity effects of life-style change and anti-inflammatory interventions after conditional inactivation of the activin receptor ALK7

“…For immunoblotting analysis, proteins were precipitated from the organic phase obtained with the TRIzol reagent (see above) as previously described (Srivastava et al, 2020). Protein pellets were dissolved in sample buffer, supplemented with βmercaptoethanol and heated at 95°C for 10 min.…”