Quantification of Bone Fatty Acid Metabolism and Its Regulation by Adipocyte Lipoprotein Lipase

被引:42
作者
Bartelt, Alexander [1 ,2 ,6 ]
Koehne, Till [3 ,4 ]
Toedter, Klaus [1 ]
Reimer, Rudolph [5 ]
Mueller, Brigitte [1 ,2 ]
Behler-Janbeck, Friederike [1 ,2 ]
Heeren, Joerg [1 ]
Scheja, Ludger [1 ]
Niemeier, Andreas [1 ,2 ]
机构
[1] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, Martinistr 52, D-20246 Hamburg, Germany
[2] Univ Med Ctr Hamburg Eppendorf, Dept Orthopaed, Martinistr 52, D-20246 Hamburg, Germany
[3] Univ Med Ctr Hamburg Eppendorf, Dept Osteol & Biomech, Martinistr 52, D-20246 Hamburg, Germany
[4] Univ Med Ctr Hamburg Eppendorf, Dept Orthodontot, Martinistr 52, D-20246 Hamburg, Germany
[5] Heinrich Pette Inst Expt Virol, Electronmicroscopy & Microtechnol, Martinistr 52, D-20246 Hamburg, Germany
[6] Harvard Univ, Dept Genet & Complex Dis, Harvard TH Chan Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA
关键词
bone marrow adipocyte; fatty acids; lipoprotein lipase; osteoblast; bone remodeling; MARROW ADIPOSE-TISSUE; PPAR-GAMMA; IN-VIVO; OSTEOBLAST DIFFERENTIATION; ENERGY-METABOLISM; APOLIPOPROTEIN-E; MINERAL DENSITY; FISH-OIL; MICE; BROWN;
D O I
10.3390/ijms18061264
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Adipocytes are master regulators of energy homeostasis. Although the contributions of classical brown and white adipose tissue (BAT and WAT, respectively) to glucose and fatty acid metabolism are well characterized, the metabolic role of adipocytes in bone marrow remains largely unclear. Here, we quantify bone fatty acid metabolism and its contribution to systemic nutrient handling in mice. Whereas in parts of the skeleton the specific amount of nutrients taken-up from the circulation was lower than in other metabolically active tissues such as BAT or liver, the overall contribution of the skeleton as a whole organ was remarkable, placing it among the top organs involved in systemic glucose as well as fatty acid clearance. We show that there are considerable site-specific variations in bone marrow fatty acid composition throughout the skeleton and that, especially in the tibia, marrow fatty acid profiles resemble classical BAT and WAT. Using a mouse model lacking lipoprotein lipase (LPL), a master regulator of plasma lipid turnover specifically in adipocytes, we show that impaired fatty acid flux leads to reduced amounts of dietary essential fatty acids while there was a profound increase in de novo produced fatty acids in both bone marrow and cortical bone. Notably, these changes in fatty acid profiles were not associated with any gross skeletal phenotype. These results identify LPL as an important regulator of fatty acid transport to skeletal compartments and demonstrate an intricate functional link between systemic and skeletal fatty acid and glucose metabolism.
引用
收藏
页数:14
相关论文
共 53 条
[1]   PPARγ insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors [J].
Akune, T ;
Ohba, S ;
Kamekura, S ;
Yamaguchi, M ;
Chung, UI ;
Kubota, N ;
Terauchi, Y ;
Harada, Y ;
Azuma, Y ;
Nakamura, K ;
Kadowaki, T ;
Kawaguchi, H .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 113 (06) :846-855
[2]   Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation [J].
Ali, AA ;
Weinstein, RS ;
Stewart, SA ;
Parfitt, AM ;
Manolagas, SC ;
Jilka, RL .
ENDOCRINOLOGY, 2005, 146 (03) :1226-1235
[3]   WNT signaling in bone homeostasis and disease: from human mutations to treatments [J].
Baron, Roland ;
Kneissel, Michaela .
NATURE MEDICINE, 2013, 19 (02) :179-192
[4]   Altered endocannabinoid signalling after a high-fat diet in Apoe-/- mice: relevance to adipose tissue inflammation, hepatic steatosis and insulin resistance [J].
Bartelt, A. ;
Orlando, P. ;
Mele, C. ;
Ligresti, A. ;
Toedter, K. ;
Scheja, L. ;
Heeren, J. ;
Di Marzo, V. .
DIABETOLOGIA, 2011, 54 (11) :2900-2910
[5]  
BARTELT A, 2012, J MOL MED, V90, P887, DOI DOI 10.1007/s00109-012-0858-3
[6]   Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport [J].
Bartelt, Alexander ;
John, Clara ;
Schaltenberg, Nicola ;
Berbee, Jimmy F. P. ;
Worthmann, Anna ;
Cherradi, M. Lisa ;
Schlein, Christian ;
Piepenburg, Julia ;
Boon, Mariette R. ;
Rinninger, Franz ;
Heine, Markus ;
Toedter, Klaus ;
Niemeier, Andreas ;
Nilsson, Stefan K. ;
Fischer, Markus ;
Wijers, Sander L. ;
Lichtenbelt, Wouter van Marken ;
Scheja, Ludger ;
Rensen, Patrick C. N. ;
Heeren, Joerg .
NATURE COMMUNICATIONS, 2017, 8
[7]   Hepatic lipase is expressed by osteoblasts and modulates bone remodeling in obesity [J].
Bartelt, Alexander ;
Beil, F. Timo ;
Mueller, Brigitte ;
Koehne, Till ;
Yorgan, Timur A. ;
Heine, Markus ;
Yilmaz, Tayfun ;
Ruether, Wolfgang ;
Heeren, Joerg ;
Schinke, Thorsten ;
Niemeier, Andreas .
BONE, 2014, 62 :90-98
[8]   Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browning [J].
Bartelt, Alexander ;
Weigelt, Clara ;
Cherradi, M. Lisa ;
Niemeier, Andreas ;
Thoedter, Klaus ;
Heeren, Joerg ;
Scheja, Ludger .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2013, 1831 (05) :934-942
[9]   The holy grail of metabolic disease: brown adipose tissue [J].
Bartelt, Alexander ;
Heeren, Joerg .
CURRENT OPINION IN LIPIDOLOGY, 2012, 23 (03) :190-195
[10]   Brown adipose tissue activity controls triglyceride clearance [J].
Bartelt, Alexander ;
Bruns, Oliver T. ;
Reimer, Rudolph ;
Hohenberg, Heinz ;
Ittrich, Harald ;
Peldschus, Kersten ;
Kaul, Michael G. ;
Tromsdorf, Ulrich I. ;
Weller, Horst ;
Waurisch, Christian ;
Eychmueller, Alexander ;
Gordts, Philip L. S. M. ;
Rinninger, Franz ;
Bruegelmann, Karoline ;
Freund, Barbara ;
Nielsen, Peter ;
Merkel, Martin ;
Heeren, Joerg .
NATURE MEDICINE, 2011, 17 (02) :200-U93