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


CONCLUSIONS
Based on our results, we conclude that histamine plays a role in the development of HFD-induced obesity.
Jørgensen
Emilie A
EA
Cluster for Molecular Imaging, Department of Medical Physiology, University of Copenhagen, Copenhagen, Denmark.
Vogelsang
Thomas W
TW
Knigge
Ulrich
U
Watanabe
Takeshi
T
Warberg
Jørgen
J
Kjaer
Andreas
A
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000502:physiology; D004041:Dietary Fats / Q000378:metabolism*; D002149:Energy Intake / Q000502:physiology*; D006632:Histamine / Q000172:deficiency / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin; D018709:Statistics, Nonparametric
D004041:Dietary Fats; D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D006632:Histamine; D006640:Histidine Decarboxylase