Abstract

We found previously that white adipose tissue (WAT) hyperplasia in obese mice was limited by dietary omega-3 polyunsaturated fatty acids (omega-3 PUFA). Here we aimed to characterize the underlying mechanism. C57BL/6N mice were fed a high-fat diet supplemented or not with omega-3 PUFA for one week or eight weeks; mice fed a standard chow diet were also used. In epididymal WAT (eWAT), DNA content was quantified, immunohistochemical analysis was used to reveal the size of adipocytes and macrophage content, and lipidomic analysis and a gene expression screen were performed to assess inflammatory status. The stromal-vascular fraction of eWAT, which contained most of the eWAT cells, except for adipocytes, was characterized using flow cytometry. Omega-3 PUFA supplementation limited the high-fat diet-induced increase in eWAT weight, cell number (DNA content), inflammation, and adipocyte growth. eWAT hyperplasia was compromised due to the limited increase in the number of preadipocytes and a decrease in the number of endothelial cells. The number of leukocytes and macrophages was unaffected, but a shift in macrophage polarization towards a less inflammatory phenotype was observed. Our results document that the counteraction of eWAT hyperplasia by omega-3 PUFA in dietary-obese mice reflects an effect on the number of adipose lineage and endothelial cells.

Highlights

  • An unhealthy lifestyle, including overnutrition, is the main driving force behind the recent pandemic of obesity and associated diseases

  • C57BL/6N male mice were fed either a standard (STD) or high-fat (HFD) diet or a high-fat diet supplemented with omega-3 PUFA (HFF) for one or eight weeks starting at 13 weeks of age

  • Both the HFD and HFF diet increased the body weight and epididymal WAT (eWAT) weight at both Week 1 and Week 8 compared to the STD diet, with no impact of omega-3 PUFA on body weight compared to HFD

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Summary

Introduction

An unhealthy lifestyle, including overnutrition, is the main driving force behind the recent pandemic of obesity and associated diseases. Obesity is defined as an excessive accumulation of body fat, namely in the form of white adipose tissue (WAT; [1]) This tissue is characterized by extreme plasticity, and fat depot-specific functional and structural heterogeneity (reviewed in [2,3,4]). Sufficient capacity for WAT expansion is essential to prevent a spillover of fatty acids and lipotoxic damage of insulin signalling in other tissues [5]. Both an insufficient amount of WAT as well as hypertrophic WAT can lead to harmful systemic metabolic consequences

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