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High ApoD protein level in the round ligament fat depot of severely obese women is associated with an improved inflammatory profile

Abstract

Purpose

Apolipoprotein D (ApoD) is a lipocalin participating in lipid transport. It binds to a variety of ligands, with a higher affinity for arachidonic acid, and is thought to have a diverse array of functions. We investigated a potential role for ApoD in insulin sensitivity, inflammation, and thrombosis—processes related to lipid metabolism—in severely obese women.

Methods

We measured ApoD expression in a cohort of 44 severely obese women including dysmetabolic and non-dysmetabolic patients. Physical and metabolic characteristics of these women were determined from anthropometric measurements and blood samples. ApoD was quantified at the mRNA and protein levels in samples from three intra-abdominal adipose tissues (AT): omental, mesenteric and round ligament (RL).

Results

ApoD protein levels were highly variable between AT of the same individual. High ApoD protein levels, particularly in the RL depot, were linked to lower plasma insulin levels (−40%, p = 0.015) and insulin resistance (−47%, p= 0.022), and increased insulin sensitivity (+10%, p = 0.008). Lower circulating pro-inflammatory PAI-1 (−39%, p = 0.001), and TNF-α (−19%, p = 0.030) levels were also correlated to high ApoD protein in the RL AT.

Conclusions

ApoD variability between AT was consistent with different accumulation efficiencies and/or metabolic functions according to the anatomic location of fat depots. Most statistically significant correlations implicated ApoD protein levels, in agreement with protein accumulation in target tissues. These correlations associated higher ApoD levels in fat depots with improved metabolic health in severely obese women.

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Acknowledgements

The Laval University Merck-Frosst/CIHR Research Chair in Obesity supported the severely obese cohort. Many thanks are also expressed to Drs V. Drapeau and F. Therrien for their very helpful assistance in plasma and adipose tissue bank management. The cooperation of subjects who participated to this study was also greatly appreciated.

Funding

For this specific study, P.M. received funding from the Quebec University Heart and Lung Institute (collaborators: D.R.J. and C.M.).

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Correspondence to Catherine Mounier.

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The authors declare that they have no conflict of interest.

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The Laval University Ethics Committee approved the experimental design (CERUL # 2004-108).

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All participants provided their written informed consent.

Electronic supplementary material

12020_2018_1621_MOESM1_ESM.xlsx

Supplementary Table S1. Body and metabolic characteristics measured in 44 severely obese women, including ApoD expression in omental, mesenteric, and round ligament adipose tissue

12020_2018_1621_MOESM2_ESM.jpg

Supplementary Figure S1. Division of the cohort into high vs. low ApoD protein expression in various fat depots. The cohort of severely obese women was divided into two groups, corresponding to high vs. low ApoD protein levels, around the median value in each AT: omental (OM, n = 44), mesenteric (ME, n = 36) and round ligament (RL, n = 43). Scatter plots show the distribution of relative ApoD protein levels in patient samples after division in each fat depot. A Mann–Whitney non-parametric test was used to compare groups with unequal standard deviation and show statistically significant difference; ****p < 0.0001

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Desmarais, F., Bergeron, KF., Lacaille, M. et al. High ApoD protein level in the round ligament fat depot of severely obese women is associated with an improved inflammatory profile. Endocrine 61, 248–257 (2018). https://doi.org/10.1007/s12020-018-1621-5

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Keywords

  • Apolipoprotein D
  • Obesity
  • Round ligament
  • Insulin
  • Plasminogen activator inhibitor-1
  • Tumor necrosis factor-α