The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis.
J. Clin. Invest.. 2003-08-01; 112(3): 423-431
DOI: 10.1172/jci17725
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1. J Clin Invest. 2003 Aug;112(3):423-31.
The endogenous cannabinoid system affects energy balance via central orexigenic
drive and peripheral lipogenesis.
Cota D(1), Marsicano G, Tschöp M, Grübler Y, Flachskamm C, Schubert M, Auer D,
Yassouridis A, Thöne-Reineke C, Ortmann S, Tomassoni F, Cervino C, Nisoli E,
Linthorst AC, Pasquali R, Lutz B, Stalla GK, Pagotto U.
Author information:
(1)Clinical Neuroendocrinology Group, Max-Planck-Institute of Psychiatry, Munich,
Germany.
Comment in
J Clin Invest. 2003 Aug;112(3):323-6.
The cannabinoid receptor type 1 (CB1) and its endogenous ligands, the
endocannabinoids, are involved in the regulation of food intake. Here we show
that the lack of CB1 in mice with a disrupted CB1 gene causes hypophagia and
leanness. As compared with WT (CB1+/+) littermates, mice lacking CB1 (CB1-/-)
exhibited reduced spontaneous caloric intake and, as a consequence of reduced
total fat mass, decreased body weight. In young CB1-/- mice, the lean phenotype
is predominantly caused by decreased caloric intake, whereas in adult CB1-/-
mice, metabolic factors appear to contribute to the lean phenotype. No
significant differences between genotypes were detected regarding locomotor
activity, body temperature, or energy expenditure. Hypothalamic CB1 mRNA was
found to be coexpressed with neuropeptides known to modulate food intake, such as
corticotropin-releasing hormone (CRH), cocaine-amphetamine-regulated transcript
(CART), melanin-concentrating hormone (MCH), and preproorexin, indicating a
possible role for endocannabinoid receptors within central networks governing
appetite. CB1-/- mice showed significantly increased CRH mRNA levels in the
paraventricular nucleus and reduced CART mRNA levels in the dorsomedial and
lateral hypothalamic areas. CB1 was also detected in epidydimal mouse adipocytes,
and CB1-specific activation enhanced lipogenesis in primary adipocyte cultures.
Our results indicate that the cannabinoid system is an essential endogenous
regulator of energy homeostasis via central orexigenic as well as peripheral
lipogenic mechanisms and might therefore represent a promising target to treat
diseases characterized by impaired energy balance.
DOI: 10.1172/JCI17725
PMCID: PMC166293
PMID: 12897210 [Indexed for MEDLINE]