A single day of high-fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice
Kuipers, Eline N. ; Held, Ntsiki M. ; Het Panhuis, Wietse In; Modder, Melanie ; Ruppert, Philip M.M. ; Kersten, Sander ; Kooijman, Sander ; Guigas, Bruno ; Houtkooper, Riekelt H. ; Rensen, Patrick C.N. ; Boon, Mariëtte R. - \ 2019
American Journal of Physiology. Endocrinology and Metabolism 317 (2019)5. - ISSN 0193-1849 - p. E820 - E830.
brown adipose tissue - high-fat diet - lipid accumulation - macrophage - mitochondrial dynamics
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. Wild-type mice were fed a HFD for 0, 1, 3, or 7 days. Within 1 day of HFD, BAT weight and lipid content were increased. HFD also immediately reduced insulin-stimulated glucose uptake by BAT, indicating rapid induction of insulin resistance. This was accompanied by a tendency toward a reduced uptake of triglyceride-derived fatty acids by BAT. Mitochondrial mass and Ucp1 expression were unaltered, whereas after 3 days of HFD, markers of mitochondrial dynamics suggested induction of a more fused mitochondrial network. Additionally, HFD also increased macrophage markers in BAT after 3 days of HFD. Counterintuitively, the switch to HFD was accompanied by an acute rise in core body temperature. We showed that a single day of HFD feeding is sufficient to induce the first signs of whitening and insulin resistance in BAT, which reduces the uptake of glucose and triglyceride-derived fatty acids. BAT whitening and insulin resistance are 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.
A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening
Berg, Rosa van den; Kooijman, Sander ; Noordam, Raymond ; Ramkisoensing, Ashna ; Abreu-Vieira, Gustavo ; Tambyrajah, Lauren L. ; Dijk, Wieneke ; Ruppert, Philip ; Mol, Isabel M. ; Kramar, Barbara ; Caputo, Rosanna ; Puig, Laura Sardón ; Ruiter, Evelien M. de; Kroon, Jan ; Hoekstra, Menno ; Sluis, Ronald J. van der; Meijer, Onno C. ; Willems van Dijk, Ko ; Kerkhof, Linda W.M. van; Christodoulides, Constantinos ; Karpe, Fredrik ; Gerhart-Hines, Zachary ; Kersten, Sander ; Meijer, Johanna H. ; Coomans, Claudia P. ; Heemst, Diana van; Biermasz, Nienke R. ; Rensen, Patrick C.N. - \ 2018
Cell Reports 22 (2018)13. - ISSN 2211-1247 - p. 3521 - 3533.
angiopoietin-like 4 - APOE3-Leiden.CETP mice - brown adipose tissue - circadian rhythm - diurnal rhythm - fatty acids - lipoprotein lipase - postprandial lipid response - triglycerides
Many favorable metabolic effects have been attributed to thermogenic activity of brown adipose tissue (BAT). Yet, time of day has rarely been considered in this field of research. Here, we show that a diurnal rhythm in BAT activity regulates plasma lipid metabolism. We observed a high-amplitude rhythm in fatty acid uptake by BAT that synchronized with the light/dark cycle. Highest uptake was found at the onset of the active period, which coincided with high lipoprotein lipase expression and low angiopoietin-like 4 expression by BAT. Diurnal rhythmicity in BAT activity determined the rate at which lipids were cleared from the circulation, thereby imposing the daily rhythm in plasma lipid concentrations. In mice as well as humans, postprandial lipid excursions were nearly absent at waking. We anticipate that diurnal BAT activity is an important factor to consider when studying the therapeutic potential of promoting BAT activity. van den Berg et al. show a strong circadian rhythm in fatty acid uptake by brown adipose tissue that peaks at wakening regardless of the light exposure period. Consequently, postprandial lipid handling by brown adipose tissue is highest at wakening, resulting in the lowest postprandial plasma lipid excursions.