Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

ApoA1 Deficiency Reshapes the Phenotypic and Molecular Characteristics of Bone Marrow Adipocytes in Mice

Version 1 : Received: 22 March 2022 / Approved: 24 March 2022 / Online: 24 March 2022 (05:26:34 CET)

A peer-reviewed article of this Preprint also exists.

Kastrenopoulou, A.; Kypreos, K.E.; Papachristou, N.I.; Georgopoulos, S.; Mastora, I.; Papadimitriou-Olivgeri, I.; Spentzopoulou, A.; Nikitovic, D.; Kontogeorgakos, V.; Blair, H.C.; Papachristou, D.J. ApoA1 Deficiency Reshapes the Phenotypic and Molecular Characteristics of Bone Marrow Adipocytes in Mice. Int. J. Mol. Sci. 2022, 23, 4834. Kastrenopoulou, A.; Kypreos, K.E.; Papachristou, N.I.; Georgopoulos, S.; Mastora, I.; Papadimitriou-Olivgeri, I.; Spentzopoulou, A.; Nikitovic, D.; Kontogeorgakos, V.; Blair, H.C.; Papachristou, D.J. ApoA1 Deficiency Reshapes the Phenotypic and Molecular Characteristics of Bone Marrow Adipocytes in Mice. Int. J. Mol. Sci. 2022, 23, 4834.

Journal reference: Int. J. Mol. Sci. 2022, 23, 4834
DOI: 10.3390/ijms23094834

Abstract

In the present study, we studied the effect of apolipoprotein A-1 (APOA1) on the spatial and molecular characteristics of bone marrow adipocytes, using well-characterized ApoA1 knockout mice. APOA1 is a central regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, and thus HDL; our recent work showed that deficiency of APOA1 increases bone marrow adiposity in mice. We found that ApoA1 deficient mice have greatly elevated adipocytes within their bone marrow compared to wild type counterparts. Morphologically, the increased adipocytes were similar to white adipocytes, and displayed proximal tibial-end localization. Marrow adipocytes from wild type mice were significantly fewer and did not display bone-end distribution pattern. The mRNA levels of the brown/beige adipocyte-specific markers Ucp1, Dio2, Pat2, Pgc1a, and the expression of leptin were greatly reduced in the ApoA1 knock-out in comparison to the wild-type mice. In the knock-out mice adiponectin was remarkably elevated. In keeping with the close ties of hematopoietic stem cells and marrow adipocytes, we found that the elevated adiposity in the ApoA1 knock out mice is associated with a significant reduction of the hematopoietic stem cells and common myeloid, but not common lymphoid, progenitors. Moreover, the “beiging”-related marker osteopontin and the angiogenic factor VEGF were also reduced in the ApoA1 knock-out mice, further supporting the notion that APOA1, and most probably HDL-C, regulate bone marrow microenvironment, favouring beige/brown adipocyte characteristics.

Keywords

Apolipoprotein A-1; High-density lipoprotein; Brown adipose tissue; White adipose tissue; Beige (Hybrid) adipose tissue

Subject

MEDICINE & PHARMACOLOGY, Pathology & Pathobiology

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