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

• Published in: International journal of molecular sciences 2022-04, Vol.23 (9), p.4834
• Main Authors: Kastrenopoulou, Afroditi, Kypreos, Kyriakos E, Papachristou, Nicholaos I, Georgopoulos, Stavros, Mastora, Ioulia, Papadimitriou-Olivgeri, Ioanna, Spentzopoulou, Argyro, Nikitovic, Dragana, Kontogeorgakos, Vassilios, Blair, Harry C, Papachristou, Dionysios J
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes, Beige - metabolism; Adipocytes, White - metabolism; Adiponectin; Adipose tissue; Adipose Tissue, Brown - metabolism; Adipose Tissue, White - metabolism; Angiogenesis; Animals; Apolipoprotein A; apolipoprotein A-1; Apolipoprotein A-I - genetics; Apolipoprotein A-I - metabolism; beige (hybrid) adipose tissue; Biomedical materials; Body fat; Bone marrow; Bone Marrow - metabolism; brown adipose tissue; Cholesterol; Diabetes; Flow cytometry; Hematopoietic stem cells; High density lipoprotein; Leptin; Lipid metabolism; Lipids; Localization; Metabolism; Mice; Mice, Knockout; Microenvironments; Mitochondria; Morphology; mRNA; Obesity - metabolism; Osteopontin; Progenitor cells; Signal transduction; Stem cell transplantation; Stem cells; Thermogenesis; Vascular endothelial growth factor; Vertebrae; white adipose tissue
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23094834

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 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 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 a bone-end distribution pattern. The mRNA levels of the brown/beige adipocyte-specific markers , , , and ; and the expression of leptin were greatly reduced in the 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, using flow cytometry we found that the elevated adiposity in the knockout mice is associated with a significant reduction in the compartments of hematopoietic stem cells and common myeloid, but not of the common lymphoid, progenitors. Moreover, the 'beiging'-related marker osteopontin and the angiogenic factor VEGF were also reduced in the knock-out mice, further supporting the notion that APOA1-and most probably HDL-C-regulate bone marrow microenvironment, favoring beige/brown adipocyte characteristics.