Activation of transient receptor potential vanilloid 1 channels in the nucleus of the solitary tract and activation of dynorphin input to the median preoptic nucleus contribute to impaired bat thermogenesis in diet-induced obesity

Ellen P.S. Conceição, Christian A. Reynolds, Shaun F. Morrison, Christopher J. Madden

Research output: Contribution to journalArticlepeer-review

Abstract

The impairment of cold-evoked activation of brown adipose tissue (BAT) in rats fed a high-fat diet (HFD) requires the activity of a vagal afferent to the medial nucleus of the solitary tract (mNTS). We determined the role of transient receptor potential vanilloid 1 (TRPV1) activation in the mNTS, and of a dynorphin input to the median preoptic nucleus (MnPO) in the impaired BAT thermogenic response to cold in HFD-fed rats. The levels of some linoleic acid (LA) metabolites, which can act as endogenous TRPV1 agonists, were elevated in the NTS of HFD rats compared with chow-fed rats. In HFD rats, nanoinjections of the TRPV1 antagonist, capsazepine (CPZ) in the NTS rescued the impaired BAT sympathetic nerve activity (BAT SNA) and thermogenic responses to cold. In contrast, in chow-fed rats, cold-evoked BAT SNA and BAT thermogenesis were not changed by nanoinjections of CPZ into the NTS. Axon terminals of NTS neurons that project to the dorsal lateral parabrachial nucleus (LPBd) were closely apposed to LPBd neurons that project to the MnPO. Many of the neurons in the LPBd that expressed c-fos during cold challenge were dynorphinergic. In HFD rats, nanoinjections of the k opioid receptor (KOR) antagonist, nor-bi-naltorphimine (nor-BNI), in the MnPO rescued the impaired BAT SNA and thermogenic responses to cold. These data suggest that HFD increases the content of endogenous ligands of TRPV1 in the NTS, which increases the drive to LPBd neurons that in turn release dynorphin in the MnPO to impair activation of BAT.

Original languageEnglish (US)
Article numberENEURO.0048-21.2021
JournaleNeuro
Volume8
Issue number2
DOIs
StatePublished - 2021

Keywords

  • Brown adipose
  • High-fat diet
  • K opioid
  • Overweight
  • Sympathetic nerve activity
  • Thermoregulation

ASJC Scopus subject areas

  • Neuroscience(all)

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