Temperature and species-dependent regulation of browning in retrobulbar fat

Fatemeh Rajaii,Dong Won Kim,Jiang Qian,Nicholas R Mahoney,Charles G Eberhart,Seth Blackshaw,Jianbo Pan

doi:10.1038/s41598-021-82672-9

Fatemeh Rajaii, Dong Won Kim + Show 5 more

Open Access

https://doi.org/10.1038/s41598-021-82672-9

Copy DOI

Abstract

Retrobulbar fat deposits surround the posterior retina and optic nerve head, but their function and origin are obscure. We report that mouse retrobulbar fat is a neural crest-derived tissue histologically and transcriptionally resembles interscapular brown fat. In contrast, human retrobulbar fat closely resembles white adipose tissue. Retrobulbar fat is also brown in other rodents, which are typically housed at temperatures below thermoneutrality, but is white in larger animals. We show that retrobulbar fat in mice housed at thermoneutral temperature show reduced expression of the brown fat marker Ucp1, and histological properties intermediate between white and brown fat. We conclude that retrobulbar fat can potentially serve as a site of active thermogenesis, that this capability is both temperature and species-dependent, and that this may facilitate regulation of intraocular temperature.

Highlights

Retrobulbar fat deposits surround the posterior retina and optic nerve head, but their function and origin are obscure
At 9 weeks of age, we observed that GFP expression selectively marked the nuclear envelope of retrobulbar adipocytes in Wnt1:Cre;Sun1-GFP mice but not in Cre-negative, Sun1-GFP littermate controls (Fig. 1B, C), demonstrating that murine orbital fat is derived from Wnt1-expressing neural crest progenitors
In order to better understand the function of orbital fat compared to other fat depots, we performed bulk RNA sequencing (RNA-Seq) to compare the transcriptomes of mouse orbital fat, interscapular brown fat, and two white fat depots from 9 to 10 week old CD1 male mice

Summary

Introduction

Retrobulbar fat deposits surround the posterior retina and optic nerve head, but their function and origin are obscure. Human retrobulbar fat in both healthy controls and thyroid eye disease patients morphologically resembles white fat[14,15]. While this potentially suggests a thermogenic function for retrobulbar fat in mice, this has not been demonstrated, nor have the reasons behind these potential species-specific differences been explored. The extent to which retrobulbar fat resembles other brown and white fat depots at the molecular level remains unknown for both mice and humans. These intrinsic differences may result from differences in the developmental origin of retrobulbar fat relative to trunk adipose tissues. Many other periorbital tissues—such as cranial bones, and periocular mesenchyme—are known to be derived from embryonic neural crest[17,18,19], the developmental origin of retrobulbar fat has not been characterized

Methods

Results

Conclusion