title: Four weeks high fat feeding induces insulin resistance without affecting dopamine release or gene expression patterns in the hypothalamus of C57Bl6 mice.
abstract: Obesity is associated with diminished dopaminergic neurotransmission. It remains unclear whether this is a cause or a consequence of the obese state. We hypothesized that high fat feeding, a well known trigger of obesity in diet sensitive mice, would blunt dopaminergic neurotransmission prior to the development of insulin resistance. We monitored in vivo dopamine release in the dorsomedial region of the hypothalamus, and determined hypothalamic gene expression patterns of dopamine receptors 1 and 2 (DRD1 and 2), tyrosine hydroxylase (TH) and the dopamine transporter (DAT) in C57Bl6 mice maintained on a high fat diet for 4 weeks. Also, a hyperinsulinemic euglycemic clamp was performed to evaluate the metabolic status of the mice. Mice maintained on a low fat diet served as controls. The high fat diet did not alter dopamine release in the dorsomedial hypothalamus of fed or fasted mice or the dopaminergic response to refeeding. Furthermore, gene expression levels of DRD1, DRD2, TH and DAT were not affected by high fat feeding. However, the high fat diet did hamper insulin action as evidenced by diminished glucose disposal during hyperinsulinemia (p<0.05). We show here that short term high fat feeding does not affect dopaminergic neurotransmission in the hypothalamus, whereas it does impair insulin action. This suggests that reduced dopaminergic neurotransmission in the hypothalamus of obese animal models is due to mechanism(s) that are not directly triggered by diet composition.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands. j.e.de_leeuw@lumc.nl
authors.forename: J E
authors.initials: JE
authors.lastname: de Leeuw van Weenen
authors.forename: L
authors.initials: L
authors.lastname: Hu
authors.forename: K
authors.initials: K
authors.lastname: Jansen-Van Zelm
authors.forename: M G
authors.initials: MG
authors.lastname: de Vries
authors.forename: J T
authors.initials: JT
authors.lastname: Tamsma
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
authors.forename: H
authors.initials: H
authors.lastname: Pijl
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism / Q000503:physiopathology; D007031:Hypothalamus / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D050483:Dopamine Plasma Membrane Transport Proteins; D007328:Insulin; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014446:Tyrosine 3-Monooxygenase; D005947:Glucose; D004298:Dopamine