Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans
Whittle, Andrew J
Schneider, Wolfgang J
Nature Publishing Group
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Whittle, A. J., Jiang, M., Peirce, V., Relat, J., Virtue, S., Ebinuma, H., Fukamachi, I., et al. (2015). Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans. Nature Communications, 6 (8951)https://doi.org/10.1038/ncomms9951
Thermogenesis in brown adipose tissue (BAT) is an important component of energy expenditure in mammals. Recent studies have confirmed its presence and metabolic role in humans. Defining the physiological regulation of BAT is therefore of great importance for developing strategies to treat metabolic diseases. Here we show that the soluble form of the low-density lipoprotein receptor relative, LR11/SorLA (sLR11), suppresses thermogenesis in adipose tissue in a cell-autonomous manner. Mice lacking LR11 are protected from diet-induced obesity associated with an increased browning of white adipose tissue and hypermetabolism. Treatment of adipocytes with sLR11 inhibits thermogenesis via the bone morphogenetic protein/TGFβ signalling pathway and reduces Smad phosphorylation. In addition, sLR11 levels in humans are shown to positively correlate with body mass index and adiposity. Given the need for tight regulation of a tissue with a high capacity for energy wastage, we propose that LR11 plays an energy conserving role that is exaggerated in states of obesity.
AW and AVP were supported by FP7 – BetaBAT, BBSRC (BB/J009865/1), the British Heart Foundation (PG/12/53/29714) and MDU MRC. MJ and HB were supported by Japan Health and Labour Sciences Research grant (H22-rinkensui-ippan-001) and Grants-in–aid for Scientific Research from Japanese Ministry of Education, Culture, Sports, Science and Technology (24390231 and 24790907). VP was supported by Wellcome Trust and the Cambridge Overseas Trust. JR was supported by Ministerio de Educación, through “Programa Nacional de Movilidad de Recursos Humanos del Plan Nacional de I-D+i 2008-2011 (Subprograma de Estancias de Movilidad en el Extranjero “José Castillejo” para jóvenes Doctores, ref: JC2011-0248). SV was supported by MRC. WJS was supported by the Austrian Science Fund (FWF P-20218 and P-20455). Animal work was performed at the MDU DMC Core facilities.
British Heart Foundation (PG/12/53/29714)
Medical Research Council (MC_UU_12012/5/B)
External DOI: https://doi.org/10.1038/ncomms9951
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252464
Creative Commons Attribution 4.0 International License
Licence URL: http://creativecommons.org/licenses/by/4.0/
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