Maturation of White Adipose Tissue Function in C57BL/6j Mice From Weaning to Young Adulthood.

Andrea Kodde,Kees Van Limpt,Jaap Keijer,Eefje Engels,Annemarie Oosting,Eline M Van Der Beek

doi:10.3389/fphys.2019.00836

Abstract

White adipose tissue (WAT) distribution and WAT mitochondrial function contribute to total body metabolic health throughout life. Nutritional interventions starting in the postweaning period may impact later life WAT health and function. We therefore assessed changes in mitochondrial density and function markers in WAT depots of young mice. Inguinal (ING), epididymal (EPI) and retroperitoneal (RP) WAT of 21, 42 and 98 days old C57BL/6j mice was collected. Mitochondrial density [citrate synthase (CS), mtDNA] and function [subunits of oxidative phosphorylation complexes (OXPHOS)] markers were analyzed, together with gene expression of browning markers (Ucp1, Cidea). mRNA of ING WAT of 21 and 98 old mice was sequenced to further investigate functional changes of the mitochondria and alterations in cell populations. CS levels decreased significantly over time in all depots. ING showed most pronounced changes, including significantly decreased levels of OXPHOS complex I, II, and III subunits and gene expression of Ucp1 (PN21-42 and PN42-98) and Cidea (PN42-98). White adipocyte markers were higher at PN98 in ING WAT. Analyses of RNA sequence data showed that the mitochondrial functional profile changed over time from “growth-supporting” mitochondria focused on ATP production (and dissipation), to more steady-state mitochondria with more diverse functions and higher biosynthesis. Mitochondrial density and energy metabolism markers declined in all three depots over time after weaning. This was most pronounced in ING WAT and associated with reduced browning markers, increased whitening and an altered metabolism. In particular the PN21-42 period may provide a time window to study mitochondrial adaptation and effects of nutritional exposures relevant for later life metabolic health.

Highlights

Obesity prevalence is high in adults and considerably increased nowadays in children and adolescents (Ng et al, 2014)
In accordance with increased white adipose tissue (WAT) weight, gene expression levels of adiposity (Lep) and adipocyte expansion (Mest) markers increased over time in EPI WAT (p < 0.05 for Lep and p < 0.001 for Mest) and RP WAT (p = 0.06 for Lep and p < 0.05 for Mest), but not ING WAT (Figures 1F–K)
Lep expression levels were moderately increased in EPI and RP WAT upon western style diet (WSD) (p < 0.05 for EPI and p = 0.08 for RP WAT; Figures 1G,H), whereas Mest expression levels were unaffected upon WSD in EPI and RP WAT (Figures 1J,K)

Summary

Introduction

Obesity prevalence is high in adults and considerably increased nowadays in children and adolescents (Ng et al, 2014). Nutrition may regulate WAT function as feeding a high fat diet reduced WAT mitochondrial density (Sutherland et al, 2008), a process that is already initiated after 5 days of western style diet (WSD) (Derous et al, 2015), while caloric restriction and diets enriched in poly-unsaturated fatty acids increased WAT mitochondrial density, oxidative capacity and biogenesis (Flachs et al, 2005; Nisoli et al, 2005) Dependent on their location in the body, WAT depots differ in their impact on metabolic health (Yang et al, 2008; Bjorndal et al, 2011). Subcutaneous WAT is located directly under the skin and is shown to have a higher oxidative capacity compared to the visceral depots in mice (Schottl et al, 2015)

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Conclusion