Yellow adipocytes comprise a new adipocyte sub-type present in human bone marrow

Abstract

25During energy demanding conditions, white adipocytes store triglycerides and release fatty acids through lipolysis. 26In contrast, bone marrow adipocytes (BM-Ad) increase in size during caloric restriction, suggesting this fat depot 27 exhibits precise metabolic specificity. We found subcutaneous adipocytes (SC-Ad) and BM-Ad share 28 morphological features, but possess distinct lipid metabolism. BM-Ad show enrichment in cholesterol-oriented 29 metabolism that correlates with increased free cholesterol content, while proteins involved in lipolysis were 30 downregulated. A strong down-regulation in expression of monoacylglycerol (MG) lipase was observed leading 31 to an accumulation of major MG species and accordingly the basal and induced lipolytic responses were absent in 32 BM-Ad. These features are not recapitulated in vitro using differentiated bone marrow mesenchymal stem cells. 33Since our data demonstrate that BM-Ad comprise a distinct class of adipocytes, we propose renaming them yellow 34 adipocytes. 35 36 Keywords 37Bone Marrow adipocytes / cholesterol/lipolysis / monoacylglycerol lipase / proteomic 2 and well-studied fat deposits occur in subcutaneous regions (SC-AT) and in the abdominal cavity surrounding key 3 internal organs like the pancreas and intestines (Zwick et al, 2018). Other adipose-specific deposits also form 4 around the heart, kidney, prostate in men and mammary glands in women (Zwick et al, 2018). In addition to WAT, 5 mammals also possess brown adipose tissue (BAT) located in the interscapular and supraclavicular regions, 6 representing less than 5% of the total fat mass (Leitner et al, 2017; Nedergaard et al, 2007; Saito et al, 2009; 7 Zingaretti et al, 2009). Brown adipocytes participate in non-shivering thermogenesis and possess a specific 8 morphology that includes several small lipid droplets and high mitochondria content (Bartelt & Heeren, 2014; 9 Cinti, 2001). In contrast, white adipocytes store energy as triglycerides (TG) in their unique large lipid droplet 10 (LD) after energy intake and release free fatty acids (FFA) through lipolysis in energy demanding conditions 11 (Zechner, 2015). Lipolysis occurs through a biochemical pathway that uses consecutive actions of adipose 12 triglyceride lipase (ATGL), which catalyzes the conversion of TG to diacylglycerols (DG) and hormone-sensitive 13 lipase (HSL) and hydrolyzes DAG to monoacylglycerols (MG), monoacylglycerol lipase (MAGL) and the newly 14 identified α/β hydrolase domain-containing protein 6 (ABHD6), which hydrolyzes MG to FA (Zhao et al, 2016) 15 and glycerol (Zechner, 2015). White adipocytes also have an important endocrine function as they can release 16 multiple soluble factors called adipokines, such as leptin and adiponectin (Fasshauer & Blüher, 2015). 17One intriguing adipose tissue (AT) localizes to the bone marrow called bone marrow adipose tissue (BM-AT) that 18 constitutes over 10% of the total fat mass in lean and healthy humans (Cawthorn et al, 2014). Technological 19 advances in quantitative imaging...

Interaction between adipose tissue and cancer cells: role for cancer progression

“…However, lipolysis might be different between adipocytes from bone marrow, visceral adipose tissue or subcutaneous adipose tissue. Indeed bone marrow adipocytes display a specific lipid metabolic profile compared to subcutaneous adipocytes with cholesterol biosynthesis oriented metabolism [26]. Importantly lipolysis is not induced by calorie restriction in bone marrow adipocyte due to the reduced expression of the monoacylglycerol lipase responsible of the last step of lipolysis; the hydrolysis of monoglycerides to free fatty acids and glycerol [26].…”

“…Indeed bone marrow adipocytes display a specific lipid metabolic profile compared to subcutaneous adipocytes with cholesterol biosynthesis oriented metabolism [26]. Importantly lipolysis is not induced by calorie restriction in bone marrow adipocyte due to the reduced expression of the monoacylglycerol lipase responsible of the last step of lipolysis; the hydrolysis of monoglycerides to free fatty acids and glycerol [26]. In addition with lipolysis and secretion of pro-inflammatory adipokines, cancer-associated adipocytes display fibroblast-like phenotype with the reorganisation of actin and vinculin cytoskeleton and the secretion of fibronectin and collagen 1 [27].…”

Standardised Nomenclature, Abbreviations, and Units for the Study of Bone Marrow Adiposity: Report of the Nomenclature Working Group of the International Bone Marrow Adiposity Society

“…Thus, since the 1990s, there has been an increasing diversity and lack of consensus for nomenclature relating to BMA research. Indeed, new terms continue to be proposed to this day (74). It is likely that research into BMA will continue expanding, and therefore it is essential to adopt a standardised nomenclature to provide a foundation and consensus for this growing field.…”

“…Some studies suggest that BMAds with a brown adipocyte-like phenotype can occur in the bone marrow cavity (102), and brown adipocyte-like phenotypes can be induced in vitro using cell culture models of BMAds, for example after overexpression of FoxC2 (103) or SIRT1 (103). However, recent data indicate that in vitro cell models do not reliably recapitulate the properties of BMAds in vivo (74). Indeed, microarrays show that UCP1 transcripts are not enriched in whole BM of mice or humans (104,105), nor is Ucp1 expression greater in BMAds vs. white adipocytes of mice (106).…”