Abstract
Background/objective:
Futile substrate cycling based on lipolytic release of fatty acids (FA) from intracellular triacylglycerols (TAG) and their re-esterification (TAG/FA cycling), as well as de novo FA synthesis (de novo lipogenesis (DNL)), represent the core energy-consuming biochemical activities of white adipose tissue (WAT). We aimed to characterize their roles in cold-induced thermogenesis and energy homeostasis.
Methods:
Male obesity-resistant A/J and obesity-prone C57BL/6J mice maintained at 30 °C were exposed to 6 °C for 2 or 7 days. In epididymal WAT (eWAT), TAG synthesis and DNL were determined using in vivo 2H incorporation from 2H2O into tissue TAG and nuclear magnetic resonance spectroscopy. Quantitative real-time-PCR and/or immunohistochemistry and western blotting were used to determine the expression of selected genes and proteins in WAT and liver.
Results:
The mass of WAT depots declined during cold exposure (CE). Plasma levels of TAG and non-esterified FA were decreased by day 2 but tended to normalize by day 7 of CE. TAG synthesis (reflecting TAG/FA cycle activity) gradually increased during CE. DNL decreased by day 2 of CE but increased several fold over the control values by day 7. Expression of genes involved in lipolysis, glyceroneogenesis, FA re-esterification, FA oxidation and mitochondrial biogenesis in eWAT was induced during CE. All these changes were more pronounced in obesity-resistant A/J than in B6 mice and occurred in the absence of uncoupling protein 1 in eWAT. Expression of markers of glyceroneogenesis in eWAT correlated negatively with hepatic FA synthesis by day 7 in both strains. Leptin and fibroblast growth factor 21 plasma levels were differentially affected by CE in the two mouse strains.
Conclusions:
Our results indicate integrated involvement of (i) TAG/FA cycling and DNL in WAT, and (ii) hepatic very-low-density lipoprotein-TAG synthesis in the control of blood lipid levels and provision of FA fuels for thermogenesis in cold. They suggest that lipogenesis in WAT contributes to a lean phenotype.
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Acknowledgements
The research was supported by the Czech Science Foundation (13-00871S) and the EU FP7 project DIABAT (HEALTH-F2-2011-278373). We thank J Bemova, S Hornova and D Salkova (Institute of Physiology CAS, Prague) for technical assistance; D Grahame Hardie (University of Dundee, UK) for the sheep AMPKα1 and AMPKα2 antibodies; James G Granneman (Wayne State University School of Medicine, MI, USA) for the advice regarding the TAG turnover and DNL activity measurements; Z Drahota for the useful consultations; Arild Rustan (University of Oslo, Norway) for critical reading of the manuscript; and the Reviewer for all the comments, namely, those regarding the integrated involvement of FA oxidation and TAG/FA cycling in energy dissipation in WAT.
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Flachs, P., Adamcova, K., Zouhar, P. et al. Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype. Int J Obes 41, 372–380 (2017). https://doi.org/10.1038/ijo.2016.228
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DOI: https://doi.org/10.1038/ijo.2016.228
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