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Summary: Under caloric restriction, bone marrow adipocytes (BM-Ads) do not decrease in size compared to white adipocytes, suggesting they harbor unique metabolic properties. We compare human primary BM-Ads with paired subcutaneous adipocytes (SC-Ads) using proteomic and lipidomic approaches. We find that, although SC-Ads and BM-Ads share similar morphological features, they possess distinct lipid metabolism. Although BM-Ad shows enrichment in proteins involved in cholesterol metabolism, correlating with increased free cholesterol content, proteins involved in lipolysis were downregulated. In particular, monoacylglycerol lipase expression is strongly reduced in BM-Ads, leading to monoacylglycerol accumulation. Consequently, basal and induced lipolytic responses are absent in BM-Ads, affirming their differences in metabolic fitness upon caloric restriction. These specific metabolic features are not recapitulated in vitro using common protocols to differentiate bone marrow mesenchymal stem cells. Thus, contrary to classical SC-Ads, BM-Ads display a specific lipid metabolism, as they are devoid of lipolytic activity and exhibit a cholesterol-orientated metabolism. : Attané et al. show that, although human bone marrow adipocytes (BM-Ads) resemble classic white adipocytes on a morphological level, their lipid metabolism is highly specific. They are devoid of lipolytic activity, one of the main metabolic functions of white adipocytes, which explains why they behave like a preserved lipid source under energy-demanding conditions. Keywords: bone marrow adipocytes, cholesterol, lipolysis, monoacylglycerol lipase, proteomic, adipose tissue, bone marrow fat