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Inflammation in VTA Caused by HFD Induces Activation of Dopaminergic Neurons Accompanied by Binge-like Eating

Binge eating is a characteristic symptom observed in obese individuals that is related to dysfunction of dopaminergic neurons (DNs). Intermittent administration of a high-fat diet (HFD) is reported to induce binge-like eating, but the underlying mechanisms remain unclear. We generated dopaminergic n...

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Autores principales: Sun, Runan, Sugiyama, Mariko, Wang, Sixian, Kuno, Mitsuhiro, Sasaki, Tomoyuki, Hirose, Tomonori, Miyata, Takashi, Kobayashi, Tomoko, Tsunekawa, Taku, Onoue, Takeshi, Yasuda, Yoshinori, Takagi, Hiroshi, Hagiwara, Daisuke, Iwama, Shintaro, Suga, Hidetaka, Arima, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502544/
https://www.ncbi.nlm.nih.gov/pubmed/36145208
http://dx.doi.org/10.3390/nu14183835
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author Sun, Runan
Sugiyama, Mariko
Wang, Sixian
Kuno, Mitsuhiro
Sasaki, Tomoyuki
Hirose, Tomonori
Miyata, Takashi
Kobayashi, Tomoko
Tsunekawa, Taku
Onoue, Takeshi
Yasuda, Yoshinori
Takagi, Hiroshi
Hagiwara, Daisuke
Iwama, Shintaro
Suga, Hidetaka
Arima, Hiroshi
author_facet Sun, Runan
Sugiyama, Mariko
Wang, Sixian
Kuno, Mitsuhiro
Sasaki, Tomoyuki
Hirose, Tomonori
Miyata, Takashi
Kobayashi, Tomoko
Tsunekawa, Taku
Onoue, Takeshi
Yasuda, Yoshinori
Takagi, Hiroshi
Hagiwara, Daisuke
Iwama, Shintaro
Suga, Hidetaka
Arima, Hiroshi
author_sort Sun, Runan
collection PubMed
description Binge eating is a characteristic symptom observed in obese individuals that is related to dysfunction of dopaminergic neurons (DNs). Intermittent administration of a high-fat diet (HFD) is reported to induce binge-like eating, but the underlying mechanisms remain unclear. We generated dopaminergic neuron specific IKKβ deficient mice (KO) to examine the effects of inflammation in DNs on binge-like eating under inflammatory conditions associated with HFD. After administration of HFD for 4 weeks, mice were fasted for 24 h, and then the consumption of HFD was measured for 2 h. We also evaluated that the mRNA expressions of inflammatory cytokines, glial markers, and dopamine signaling-related genes in the ventral tegmental area (VTA) and striatum. Moreover, insulin was administered intraventricularly to assess downstream signaling. The consumption of HFD was significantly reduced, and the phosphorylation of AKT in the VTA was significantly increased in female KO compared to wild-type (WT) mice. Analyses of mRNA expressions revealed that DNs activity and inflammation in the VTA were significantly decreased in female KO mice. Thus, our data suggest that HFD-induced inflammation with glial cell activation in the VTA affects DNs function and causes abnormal eating behaviors accompanied by insulin resistance in the VTA of female mice.
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spelling pubmed-95025442022-09-24 Inflammation in VTA Caused by HFD Induces Activation of Dopaminergic Neurons Accompanied by Binge-like Eating Sun, Runan Sugiyama, Mariko Wang, Sixian Kuno, Mitsuhiro Sasaki, Tomoyuki Hirose, Tomonori Miyata, Takashi Kobayashi, Tomoko Tsunekawa, Taku Onoue, Takeshi Yasuda, Yoshinori Takagi, Hiroshi Hagiwara, Daisuke Iwama, Shintaro Suga, Hidetaka Arima, Hiroshi Nutrients Article Binge eating is a characteristic symptom observed in obese individuals that is related to dysfunction of dopaminergic neurons (DNs). Intermittent administration of a high-fat diet (HFD) is reported to induce binge-like eating, but the underlying mechanisms remain unclear. We generated dopaminergic neuron specific IKKβ deficient mice (KO) to examine the effects of inflammation in DNs on binge-like eating under inflammatory conditions associated with HFD. After administration of HFD for 4 weeks, mice were fasted for 24 h, and then the consumption of HFD was measured for 2 h. We also evaluated that the mRNA expressions of inflammatory cytokines, glial markers, and dopamine signaling-related genes in the ventral tegmental area (VTA) and striatum. Moreover, insulin was administered intraventricularly to assess downstream signaling. The consumption of HFD was significantly reduced, and the phosphorylation of AKT in the VTA was significantly increased in female KO compared to wild-type (WT) mice. Analyses of mRNA expressions revealed that DNs activity and inflammation in the VTA were significantly decreased in female KO mice. Thus, our data suggest that HFD-induced inflammation with glial cell activation in the VTA affects DNs function and causes abnormal eating behaviors accompanied by insulin resistance in the VTA of female mice. MDPI 2022-09-16 /pmc/articles/PMC9502544/ /pubmed/36145208 http://dx.doi.org/10.3390/nu14183835 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sun, Runan
Sugiyama, Mariko
Wang, Sixian
Kuno, Mitsuhiro
Sasaki, Tomoyuki
Hirose, Tomonori
Miyata, Takashi
Kobayashi, Tomoko
Tsunekawa, Taku
Onoue, Takeshi
Yasuda, Yoshinori
Takagi, Hiroshi
Hagiwara, Daisuke
Iwama, Shintaro
Suga, Hidetaka
Arima, Hiroshi
Inflammation in VTA Caused by HFD Induces Activation of Dopaminergic Neurons Accompanied by Binge-like Eating
title Inflammation in VTA Caused by HFD Induces Activation of Dopaminergic Neurons Accompanied by Binge-like Eating
title_full Inflammation in VTA Caused by HFD Induces Activation of Dopaminergic Neurons Accompanied by Binge-like Eating
title_fullStr Inflammation in VTA Caused by HFD Induces Activation of Dopaminergic Neurons Accompanied by Binge-like Eating
title_full_unstemmed Inflammation in VTA Caused by HFD Induces Activation of Dopaminergic Neurons Accompanied by Binge-like Eating
title_short Inflammation in VTA Caused by HFD Induces Activation of Dopaminergic Neurons Accompanied by Binge-like Eating
title_sort inflammation in vta caused by hfd induces activation of dopaminergic neurons accompanied by binge-like eating
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502544/
https://www.ncbi.nlm.nih.gov/pubmed/36145208
http://dx.doi.org/10.3390/nu14183835
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