Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype

Int J Obes (Lond). 2017 Mar;41(3):372-380. doi: 10.1038/ijo.2016.228. Epub 2016 Dec 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / metabolism*
  • Animals
  • Cold Temperature*
  • Disease Models, Animal
  • Lipid Metabolism
  • Lipogenesis / genetics
  • Lipogenesis / physiology*
  • Lipoproteins, VLDL / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / genetics
  • Obesity / metabolism
  • Phenotype
  • Thermogenesis / genetics
  • Thermogenesis / physiology*
  • Thinness / genetics
  • Thinness / metabolism*


  • Lipoproteins, VLDL