249 - A single day of high fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice (ID 731)
- Melanie Modder, Netherlands
- Eline N. Kuipers, Netherlands
- Ntsiki M. Held, Netherlands
- Wietse In het Panhuis, Netherlands
- Philip M. Ruppert, Netherlands
- Sander Kersten, Netherlands
- Sander Kooijman, Netherlands
- Bruno Guisas, Netherlands
- Riekelt Houtkooper, Netherlands
- Patrick Rensen, Netherlands
- Mariëtte Boon, Netherlands
Abstract
Background and Aims
Brown adipose tissue (BAT) catabolizes glucose and fatty acids to produce heat and thereby contributes to energy expenditure. Long-term high fat diet (HFD) feeding results in so-called ‘whitening’ of BAT characterized by increased lipid deposition, mitochondrial dysfunction and reduced fat oxidation. The aim of the current study was to unravel the rate and related mechanisms by which HFD induces BAT whitening and insulin resistance.
Methods
Wild-type mice were fed a HFD for 0, 1, 3 or 7 days. After termination, insulin-stimulated [14C]deoxyglucose uptake and uptake of glycerol tri[3H]oleate-labeled TG-rich lipoprotein-like particles was determined, organs were weighed, and histology was performed.
Results
Within one day of HFD BAT weight and lipid content were increased. HFD also immediately reduced insulin-stimulated deoxyglucose uptake and fatty acid uptake by BAT. Mitochondrial mass and Ucp1 expression were unaltered, while after 3 days of HFD a more fused mitochondrial network was induced accompanied by increased macrophage markers in BAT. Counterintuitively, the switch to HFD was accompanied by an acute rise in core body temperature.
Conclusions
A single day of HFD feeding is sufficient to induce the first signs of whitening and insulin resistance in BAT, which relduces the uptake of glucose and triglyceride-derived fatty acids. BAT whitening and insulin resistance is likely sustained by reduced mitochondrial oxidation due to changes in mitochondrial dynamics and macrophage infiltration, respectively. Likely, the switch to HFD swiftly induces thermogenesis in other metabolic organs, which allows attenuation of BAT thermogenesis.
