title: Transforming growth factor-beta in the brain enhances fat oxidation via noradrenergic neurons in the ventromedial and paraventricular hypothalamic nucleus.
abstract: We have previously reported that intracisternal administration of TGF-beta induces an increase in fat oxidation and that intracisternal administration of anti-TGF-beta antibody partially inhibits an increase in fat oxidation during treadmill running in rats. These results indicate a regulatory role of that TGF-beta in the brain on fat oxidation during exercise. However, it is not clear how TGF-beta in the brain enhance fat oxidation. We hypothesized that TGF-beta in the brain elicits its regulatory effects on fat oxidation via hypothalamic noradrenergic neurons, because some reports have demonstrated the important role of hypothalamic noradrenergic neurons in the regulation of fat oxidation during and after exercise. To examine this hypothesis, we measured the extracellular noradrenaline (NA) levels in the paraventricular hypothalamic nucleus (PVH), ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area, which are especially important in the regulation of energy metabolism, after intracisternal administration of TGF-beta by using an in vivo brain microdialysis. Microdialysis study revealed that intracisternal administration of TGF-beta3 caused increases in the NA levels in the PVH and VMH. Then, we investigated the impact of impairment of noradrenergic neurons in the PVH and VMH by neurotoxin 6-hydroxydopamine microinjection (NA-lesion) on the action of intracisternal administration of TGF-beta. The NA lesion completely abolished the regulatory effect of TGF-beta on fat oxidation. These results suggest that TGF-beta in the brain enhances fat oxidation via noradrenergic neurons in the PVH and VMH.
authors.affiliation: Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Fujikawa
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Matsumura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Inoue
authors.forename: Tohru
authors.initials: T
authors.lastname: Fushiki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005223:Fats / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects*; D016627:Oxidopamine / Q000633:toxicity; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology* / Q000293:injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D053782:Transforming Growth Factor beta3 / Q000097:blood / Q000494:pharmacology*; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology* / Q000293:injuries
chemical_list: D005223:Fats; D053782:Transforming Growth Factor beta3; D016627:Oxidopamine; D009638:Norepinephrine