title: Cold Exposure Partially Corrects Disturbances in Lipid Metabolism in a Male Mouse Model of Glucocorticoid Excess.
abstract: High glucocorticoid concentrations are accompanied by metabolic side effects such as high plasma triglyceride (TG) concentrations. Liver, brown adipose tissue (BAT) and white adipose tissue are important regulators of plasma TG. Exposure to 4°C reduces plasma TG concentrations, and we therefore aimed to study the interaction between glucocorticoid excess and 24 hours of exposure to 4°C on lipid metabolism. For this, mice were implanted with 50-mg corticosterone or control pellets and housed for 24 hours at 23°C or 4°C 1 week later, after which various aspects of TG metabolism in liver, BAT, and white adipose tissue were studied. Corticosterone treatment resulted in a 3.8-fold increase of plasma TG concentrations. Increased TG was normalized by cold exposure, an effect still present 24 hours after cold exposure. Corticosterone treatment increased hepatic TG content by 3.5-fold and provoked secretion of large, TG-rich very low density lipoprotein particles. Cold exposure reduced very low density lipoprotein-TG secretion by approximately 50%. Corticosterone strongly decreased BAT activity: BAT weight increased by 3.5-fold, whereas uncoupling protein 1 (Ucp1) mRNA expression and Ucp1 protein content of BAT were reduced by 75% and 60%, respectively. Cold exposure partially normalized these parameters of BAT activity. The uptake of TG by BAT was not affected by corticosterone treatment but was increased 4.5-fold upon cold exposure. In conclusion, cold exposure normalizes corticosterone-induced hypertriglyceridemia, at least partly via activating BAT.
authors.affiliation: Department of Internal Medicine (J.C.v.d.B., J.S., A.P.N.T., A.G.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Medicine (M.R.B., P.C.N.R., O.C.M.), Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Einthoven Laboratory of Experimental Vascular Medicine (M.R.B., P.C.N.R., O.C.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: van den Beukel
authors.affiliation: Department of Internal Medicine (J.C.v.d.B., J.S., A.P.N.T., A.G.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Medicine (M.R.B., P.C.N.R., O.C.M.), Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Einthoven Laboratory of Experimental Vascular Medicine (M.R.B., P.C.N.R., O.C.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Mariëtte R
authors.initials: MR
authors.lastname: Boon
authors.affiliation: Department of Internal Medicine (J.C.v.d.B., J.S., A.P.N.T., A.G.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Medicine (M.R.B., P.C.N.R., O.C.M.), Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Einthoven Laboratory of Experimental Vascular Medicine (M.R.B., P.C.N.R., O.C.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Jacobie
authors.initials: J
authors.lastname: Steenbergen
authors.affiliation: Department of Internal Medicine (J.C.v.d.B., J.S., A.P.N.T., A.G.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Medicine (M.R.B., P.C.N.R., O.C.M.), Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Einthoven Laboratory of Experimental Vascular Medicine (M.R.B., P.C.N.R., O.C.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.affiliation: Department of Internal Medicine (J.C.v.d.B., J.S., A.P.N.T., A.G.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Medicine (M.R.B., P.C.N.R., O.C.M.), Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Einthoven Laboratory of Experimental Vascular Medicine (M.R.B., P.C.N.R., O.C.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Onno C
authors.initials: OC
authors.lastname: Meijer
authors.affiliation: Department of Internal Medicine (J.C.v.d.B., J.S., A.P.N.T., A.G.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Medicine (M.R.B., P.C.N.R., O.C.M.), Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Einthoven Laboratory of Experimental Vascular Medicine (M.R.B., P.C.N.R., O.C.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
authors.affiliation: Department of Internal Medicine (J.C.v.d.B., J.S., A.P.N.T., A.G.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Medicine (M.R.B., P.C.N.R., O.C.M.), Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Einthoven Laboratory of Experimental Vascular Medicine (M.R.B., P.C.N.R., O.C.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Aldo
authors.initials: A
authors.lastname: Grefhorst
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001833:Body Temperature Regulation; D003080:Cold Temperature; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology*; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D005938:Glucocorticoids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D014280:Triglycerides; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D003345:Corticosterone