High-fat diet decreases tyrosine hydroxylase mRNA expression irrespective of obesity susceptibility in mice

Brain Res. 2009 May 1;1268:181-189. doi: 10.1016/j.brainres.2009.02.075. Epub 2009 Mar 11.


Tyrosine hydroxylase is the rate-limiting enzyme in the synthesis of dopamine, a key neurotransmitter in the regulation of food intake. This study examined tyrosine hydroxylase mRNA expression in obese mice fed a high-fat diet. After 8 week feeding of high-fat diet mice were classified as diet-induced obese and obese-resistant according to body weight gain. They were then placed on different dietary interventions including a high-fat diet, a low-fat diet and an energy-restricted high-fat diet for six weeks. The control group was fed a low-fat diet. The results revealed that tyrosine hydroxylase mRNA expression was significantly decreased in the ventral tegmental area (VTA), ventromedial hypothalamic nucleus (VMH), and substantia nigra (SN) of the high-fat diet-induced obese (-29%, -26% and -26%) and obese-resistant mice (-21%, -24% and -18%) compared to controls. After switching the diet from high to low-fat diet tyrosine hydroxylase mRNA was increased in the VTA, VMH, and SN of the diet-induced obese mice and in the VMH, and SN of the obese-resistant mice. Energy restriction, even with high-fat feeding, reduced tyrosine hydroxylase mRNA expression in the VTA, VMH, and SN compared to controls. In addition, tyrosine hydroxylase mRNA expression in the VTA, VMH, and SN showed a significant negative correlation with plasma leptin levels. This study suggests that the up- or down-regulation of tyrosine hydroxylase mRNA expression in the VTA, VMH, and SN is mainly due to the intake of macronutrient type rather than body weight.

MeSH terms

  • Adipocytes, White
  • Animals
  • Body Composition
  • Body Weight / physiology
  • Brain / metabolism*
  • Diet*
  • Dietary Fats / administration & dosage*
  • Down-Regulation
  • Energy Intake
  • Genetic Predisposition to Disease
  • Insulin / blood
  • Leptin / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / diet therapy
  • Obesity / genetics
  • Obesity / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Substantia Nigra / metabolism
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism*
  • Ventral Tegmental Area / metabolism
  • Ventromedial Hypothalamic Nucleus / metabolism


  • Dietary Fats
  • Insulin
  • Leptin
  • RNA, Messenger
  • Tyrosine 3-Monooxygenase