Cidea improves the metabolic profile through expansion of adipose tissue.

Gustavo Abreu-Vieira,Barbara Cannon,Jan Nedergaard,Charlotte Mattsson,Natasa Petrovic,Peter Arner,Jurga Laurencikiene,Irina G Shabalina,Jasper M.A De Jong,Mikael Rydén,Alexander W Fischer

doi:10.1038/ncomms8433

Gustavo Abreu-Vieira, Barbara Cannon + Show 9 more

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https://doi.org/10.1038/ncomms8433

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Abstract

In humans, Cidea (cell death-inducing DNA fragmentation factor alpha-like effector A) is highly but variably expressed in white fat, and expression correlates with metabolic health. Here we generate transgenic mice expressing human Cidea in adipose tissues (aP2-hCidea mice) and show that Cidea is mechanistically associated with a robust increase in adipose tissue expandability. Under humanized conditions (thermoneutrality, mature age and prolonged exposure to high-fat diet), aP2-hCidea mice develop a much more pronounced obesity than their wild-type littermates. Remarkably, the malfunctioning of visceral fat normally caused by massive obesity is fully overcome-perilipin 1 and Akt expression are preserved, tissue degradation is prevented, macrophage accumulation is decreased and adiponectin expression remains high. Importantly, the aP2-hCidea mice display enhanced insulin sensitivity. Our data establish a functional role for Cidea and suggest that, in humans, the association between Cidea levels in white fat and metabolic health is not only correlative but also causative.

Highlights

In humans, Cidea is highly but variably expressed in white fat, and expression correlates with metabolic health
The human Cidea protein expressed in vivo had a similar size to human Cidea protein produced in vitro (Fig. 1c)
As the major effects of Cidea expression were observed in the eWAT of the transgenic mice, we propose that this fat depot has significant impact on systemic insulin sensitivity

Summary

Introduction

Cidea (cell death-inducing DNA fragmentation factor alpha-like effector A) is highly but variably expressed in white fat, and expression correlates with metabolic health. Our data establish a functional role for Cidea and suggest that, in humans, the association between Cidea levels in white fat and metabolic health is correlative and causative. In humans, Cidea is positively correlated with insulin sensitivity and healthy obesity It is unknown whether Cidea causes the metabolically healthy phenotype or merely reflects the better metabolic state. Mouse models open opportunities to establish a possible causative effect of Cidea in conferring health to an obese phenotype Using this opportunity, we humanized mice by introducing human Cidea into their white fat. The transgenic mice developed a metabolically healthy obesity, pointing to Cidea as being an important and causative factor involved in protection against the metabolic complications of obesity

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