Leptin-regulated endocannabinoids are involved in maintaining food intake

  title={Leptin-regulated endocannabinoids are involved in maintaining food intake},
  author={Vincenzo Di Marzo and Sravan Kumar Goparaju and Lei Wang and Jie Liu and Sandor Batkai and Zolt{\'a}n J{\'a}rai and Filomena Fezza and Grant I. Miura and Richard D. Palmiter and Takayuki Sugiura and George Kunos},
Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance. Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as α-melanocyte-stimulating hormone, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y. Genetic defects in anorexigenic signalling, such as mutations in the melanocortin-4 (ref. 5) or leptin receptors, cause obesity. However… 
Reciprocal modulation of sweet taste by leptin and endocannabinoids.
Findings indicate that leptin and endocannabinoids not only regulate food intake via central nervous systems but also may modulate palatability of foods by altering peripheral sweet taste responses via their cognate receptors.
The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis.
It is shown that the lack of CB1 in mice with a disrupted CB1 gene causes hypophagia and leanness, and 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.
Title Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice Permalink
The results suggest that circulating leptin, but not local endocannabinoids, may be a dominant modulator for sweet taste in lean mice; however, endOCannabinoids may become more effective modulators of sweet taste under conditions of deficient leptin signalling, possibly due to increased production of endoc cannabinoidoids in taste tissue.
Peripheral cannabinoid-1 receptor blockade restores hypothalamic leptin signaling
Ghrelin-Induced Orexigenic Effect in Rats Depends on the Metabolic Status and Is Counteracted by Peripheral CB1 Receptor Antagonism
The study highlights the importance of the animaĺs metabolic status for the effectiveness of ghrelin in promoting feeding, and suggests that the peripheral endocannabinoid system may interact with ghrelińs signal in the control of food intake under equilibrate energy balance conditions.
The role of endocannabinoids in the hypothalamic regulation of visceral function.
It is suggested that the endocannabinoid system is playing an important part in the regulation of the mentioned visceral functions and it provides the bases for further applications of cannabinoid receptor agonists and/or antagonists in visceral diseases regulated by the hypothalamus.
The role of the endocannabinoid system in the control of energy homeostasis
Research in the laboratory has indicated that endocannabinoids acting via CB1 are involved in the hunger-induced increase in food intake and are negatively regulated by leptin in brain areas involved in appetite control, suggesting that CB1 regulation of body weight involves additional peripheral targets.


Mice lacking melanin-concentrating hormone are hypophagic and lean
MCH is a critical regulator of feeding and energy balance which acts downstream of leptin and the melanocortin system, and that deletion of a gene encoding a single orexigenic peptide can result in leanness.
Leptin Increases Hypothalamic Pro-opiomelanocortin mRNA Expression in the Rostral Arcuate Nucleus
The finding that leptin reverses this effect in ob/ob, but not db/db, mice suggests that leptin stimulates arcuate nucleus POMC gene expression via a pathway involving leptin receptors, and supports the hypothesis that leptin signaling in the brain involves activation of the hypothalamic melanocortin system.
The role of neuropeptide Y in the antiobesity action of the obese gene product
RECENTLY Zhang et al.1 cloned a gene that is expressed only in adipose tissue of the mouse. The obese phenotype of theob/ob mouse is linked to a mutation in the obese gene that results in expression
Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y
It is reported here that mice deficient for NPY have normal food intake and body weight, and become hyperphagic following food deprivation, and mutants are more susceptible to seizures induced by a GABA (γ-aminobutyric acid) antagonist when treated with recombinant leptin.
Evidence suggesting that galanin (GAL), melanin-concentrating hormone (MCH), neurotensin (NT), proopiomelanocortin (POMC) and neuropeptide Y (NPY) are targets of leptin signaling in the hypothalamus.
GAL, MCH, POMC and NT are identified as non-NPY targets of leptin signaling and it is suggested that leptin's action on food intake and body weight is most likely mediated by inhibiting excitatory and stimulating inhibitory signals in the feeding circuitry.
Melanocortin receptors in leptin effects
It is shown that MC4 receptor signalling is an important mediator of leptin's effects on food intake and body weight, demonstrating a link between the two systems.
Leptin regulation of prepro-orexin and orexin receptor mRNA levels in the hypothalamus.
The results indicate that leptin inhibits a fasting-induced increase in prepro-orexin mRNA and orexin receptor 1 mRNA levels in the rat hypothalamus, while orexIn receptor 2 mRNA levels were unchanged in all situations evaluated.
Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors
This first demonstration of anandamide-induced, CB1-mediated, overeating provides important evidence for the involvement of a central cannabinoid system in the normal control of eating.