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

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 a bone-end distribution pattern. The mRNA levels of the brown/beige adipocyte-specific markers Ucp1, Dio2, Pat2, and 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, using flow cytometry we found that the elevated adiposity in the ApoA1 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 ApoA1 knock-out mice, further supporting the notion that APOA1—and most probably HDL-C—regulate bone marrow microenvironment, favoring beige/brown adipocyte characteristics.

The association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and the risk of osteoporosis among U.S. adults: analysis of NHANES data

“…Additionally, some studies have indicated that the main regulatory factors for adipocyte differentiation in bone marrow adipose tissue are PPARγ and CEBPa. The deficiency of ApoA1, the primary protein component of HDL-C, (corresponding to a reduction in high-density lipoprotein levels), may enhance the expression of Cebpa and PPARγ, thereby causing changes in the population of bone precursor cells, increasing adipocyte formation, and reducing osteoblast production [ 32 ]. Through its regulation of certain cell signaling pathways, including the tyrosine kinase receptor (RTK) system and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B pathway, HDL contributes to signaling events that impact the development, specialization, and bone-forming activity of osteoblasts [ 33 ].…”

Apolipoprotein A1 is associated with osteocalcin and bone mineral density rather than high-density lipoprotein cholesterol in Chinese postmenopausal women with type 2 diabetes mellitus

“…Recent data from experimental mice also confirmed that ApoA1 deficiency generates changes in the bone cell precursor population, can increase adipoblast and decreases osteoblast production ( 13 ). In addition, APOA1 deficiency can also influence bone metabolism by reshaping bone marrow adipocyte phenotypic and molecular characteristics ( 33 , 34 ). OC is a product of osteoblasts that accumulates in the extracellular matrix of bone.…”

Effects of Different-Syllable Aggressive Calls on Food Intake and Gene Expression in Vespertilio sinensis

“…In the group A vs. C comparison, DEGs were significantly enriched in the cholesterol metabolism and fat digestion and absorption pathways. APOA1 is the main protein found in cholesterol particles and is associated with reduced fat and carbohydrate intake [47]. lIPC is an important gene that determines cholesterol concentration and is associated with energy metabolism [48].…”