A single day of high-fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice

Eline N. Kuipers, Ntsiki M. Held, Wietse In Het Panhuis, Melanie Modder, Philip M.M. Ruppert, Sander Kersten, Sander Kooijman, Bruno Guigas, Riekelt H. Houtkooper, Patrick C.N. Rensen, Mariëtte R. Boon*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)E820-E830
JournalAmerican Journal of Physiology. Endocrinology and Metabolism
Volume317
Issue number5
DOIs
Publication statusPublished - Nov 2019

Fingerprint

Brown Adipose Tissue
High Fat Diet
Insulin Resistance
Lipids
Mitochondrial Dynamics
Fatty Acids
Thermogenesis
Glucose
Triglycerides
Macrophages
Body Temperature
Energy Metabolism
Hot Temperature
Fats
Insulin

Keywords

  • brown adipose tissue
  • high-fat diet
  • lipid accumulation
  • macrophage
  • mitochondrial dynamics

Cite this

Kuipers, Eline N. ; Held, Ntsiki M. ; In Het Panhuis, Wietse ; Modder, Melanie ; Ruppert, Philip M.M. ; Kersten, Sander ; Kooijman, Sander ; Guigas, Bruno ; Houtkooper, Riekelt H. ; Rensen, Patrick C.N. ; Boon, Mariëtte R. / A single day of high-fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice. In: American Journal of Physiology. Endocrinology and Metabolism. 2019 ; Vol. 317, No. 5. pp. E820-E830.
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abstract = "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.",
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author = "Kuipers, {Eline N.} and Held, {Ntsiki M.} and {In Het Panhuis}, Wietse and Melanie Modder and Ruppert, {Philip M.M.} and Sander Kersten and Sander Kooijman and Bruno Guigas and Houtkooper, {Riekelt H.} and Rensen, {Patrick C.N.} and Boon, {Mari{\"e}tte R.}",
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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.; In Het Panhuis, Wietse; Modder, Melanie; Ruppert, Philip M.M.; Kersten, Sander; Kooijman, Sander; Guigas, Bruno; Houtkooper, Riekelt H.; Rensen, Patrick C.N.; Boon, Mariëtte R.

In: American Journal of Physiology. Endocrinology and Metabolism, Vol. 317, No. 5, 11.2019, p. E820-E830.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A single day of high-fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice

AU - Kuipers, Eline N.

AU - Held, Ntsiki M.

AU - In Het Panhuis, Wietse

AU - Modder, Melanie

AU - Ruppert, Philip M.M.

AU - Kersten, Sander

AU - Kooijman, Sander

AU - Guigas, Bruno

AU - Houtkooper, Riekelt H.

AU - Rensen, Patrick C.N.

AU - Boon, Mariëtte R.

PY - 2019/11

Y1 - 2019/11

N2 - 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.

AB - 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.

KW - brown adipose tissue

KW - high-fat diet

KW - lipid accumulation

KW - macrophage

KW - mitochondrial dynamics

U2 - 10.1152/ajpendo.00123.2019

DO - 10.1152/ajpendo.00123.2019

M3 - Article

VL - 317

SP - E820-E830

JO - American Journal of Physiology. Endocrinology and Metabolism

JF - American Journal of Physiology. Endocrinology and Metabolism

SN - 0193-1849

IS - 5

ER -