Glutamate release mediates leptin action on energy expenditure (original) (raw)

“…More recently, however, pharmacogenetic activation of leptin-receptor-expressing POA neurons in mice was reported to induce hypothermia and to reduce energy expenditure through a glutamatergic, but not GABAergic, mechanism 112 . This involvement of glutamate is further supported by the observation that deleting vesicular glutamate transporter 2 (VGLUT2), which is needed for glutamate transmission, from leptin-receptor-expressing neurons in mice drastically reduces energy expenditure and body temperature 171 . As discussed above, the ultimate thermoregulatory effects of leptin are more likely to involve vasomotor mechanisms than BAT thermogenesis.…”

Section: Leptin and Neural Control Of Adiposementioning

“…More recently, however, pharmacogenetic activation of leptin-receptor-expressing POA neurons in mice was reported to induce hypothermia and to reduce energy expenditure through a glutamatergic, but not GABAergic, mechanism 112 . This involvement of glutamate is further supported by the observation that deleting vesicular glutamate transporter 2 (VGLUT2), which is needed for glutamate transmission, from leptin-receptor-expressing neurons in mice drastically reduces energy expenditure and body temperature 171 . As discussed above, the ultimate thermoregulatory effects of leptin are more likely to involve vasomotor mechanisms than BAT thermogenesis.…”

Section: Leptin and Neural Control Of Adiposementioning

“…Generation of LepR-Ires-Cre ( LIC ) mice and floxed Vgat ( Vgat flox/flox ) or Vglut2 ( Vglut2 flox/flox ) mice was described previously (31–33). The same breeding strategy described in the previous studies was used to obtain LIC:Vgat flox/flox mice and LIC:Vglut2 flox/flox mice (18,19). LIC:Vga flox/flox :Vglut2 flox/flox mice and their controls were obtained from breeding pairs LIC:Vga flox/flox :Vglut2 flox/flox and Vgat flox/flox :Vglut2 flox/flox mice .…”

Section: Methodsmentioning

“…LepRs in GABAergic neurons mediate a major part of the leptin action on body weight regulation, whereas those in glutamatergic neurons mediate a small part (17). We have recently demonstrated (18,19) that disruption of either γ-aminobutyric acid (GABA) or glutamate release from LepR neurons triggers obesity in mice. Importantly, LepR expression in GABAergic neurons is sufficient for leptin-mediated insulin-independent regulation of glucose homeostasis (20), suggesting a role for GABA release in mediating the leptin action.…”

Section: Introductionmentioning

“…The notion of body temperature-reducing effects by the melanocortin pathway is supported by previous findings that the melancorcortin receptor agonists suppress fever [22–24]. Since brain neural pathways, for example, the leptin neural pathway, have been demonstrated to modulate energy expenditure and therefore body temperature and are involved in episodes of rapid changes in body temperature regulation [12, 25], it would be interesting to identify the receptor(s) that mediate the action of the endogenous melanocortin α-MSH and its analogues on energy expenditure/body temperature regulation.…”

Section: Discussionmentioning

“…As previously reported [12], precalibrated sensitive transmitters (PDT-4000 G2 E-Mitter sensors, Respironics Inc. Murrysville, PA, USA) were used for performing telemetric measurements. For measuring body temperature and locomotor activity, mice were anesthetized with ketamine/xylazine and then implanted E-Mitters in the space under the skin between the scapulae.…”

Section: Methodsmentioning