Increased susceptibility to diet-induced obesity in histamine-deficient mice

Neuroendocrinology. 2006;83(5-6):289-94. doi: 10.1159/000095339. Epub 2006 Aug 22.


Background and aim: The neurotransmitter histamine is involved in the regulation of appetite and in the development of age-related obesity in mice. Furthermore, histamine is a mediator of the anorexigenic action of leptin. The aim of the present study was to investigate a possible role of histamine in the development of high-fat diet (HFD)-induced obesity.

Methods: Histamine-deficient histidine decarboxylase knock-out (HDC-KO) mice and C57BL/6J wild-type (WT) mice were given either a standard diet (STD) or HFD for 8 weeks. Body weight, 24-hour caloric intake, epididymal adipose tissue size, plasma leptin concentration and quantitative expression of leptin receptor (Ob-R) mRNA were measured.

Results: Both HDC-KO and WT mice fed an HFD for 8 weeks increased their body weight significantly more than STD-fed mice. A significant difference in body weight gain between HDC-KO mice fed an HFD or an STD was seen after 2 weeks, whereas a significant difference in body weight gain was first observed after 5 weeks in WT mice. After 8 weeks 24-hour caloric intake was significantly lower in HFD- than in STD-fed WT mice. In HDC-KO mice no difference in caloric intake was observed between HFD- and STD-fed mice. After 8 weeks epididymal adipose tissue size and plasma leptin concentration had increased significantly in HFD-fed WT and HDC-KO mice compared to their STD-fed controls. Epididymal adipose tissue size was higher in HDC-KO than WT mice, both in STD- and HFD-fed mice. A significant decrease in Ob-R mRNA in HFD-fed HDC-KO mice compared to STD-fed HDC-KO mice was observed, while no such difference was observed in WT mice.

Conclusion: Based on our results, we conclude that histamine plays a role in the development of HFD-induced obesity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Body Weight / physiology
  • Dietary Fats / metabolism*
  • Energy Intake / physiology*
  • Histamine / deficiency
  • Histamine / physiology*
  • Histidine Decarboxylase / deficiency
  • Histidine Decarboxylase / genetics
  • Histidine Decarboxylase / metabolism*
  • Hypothalamus / metabolism
  • Leptin / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / enzymology
  • Obesity / metabolism*
  • RNA, Messenger / analysis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Leptin
  • Statistics, Nonparametric


  • Dietary Fats
  • Leptin
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Leptin
  • Histamine
  • Histidine Decarboxylase