Knocking down the neuronal lactate transporter MCT2 in the arcuate nucleus of female rats increases food intake and body weight
Abstract In the arcuate nucleus of the hypothalamus, tanycyte-neuron interactions regulate glucose homeostasis and feeding behavior. Previously, we reported that monocarboxylate transporters (MCT) 1 and 4 are localized in tanycytes, whereas MCT2 is present in arcuate nucleus neurons, including orexi...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-90513-2 |
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| author | Alanis Coca Sergio López Patricio Órdenes Vania Sepúlveda Diego Cuevas Andrés Villarroel Javiera Álvarez-Indo Patricia V. Burgos Estefanía Tarifeño Roberto Elizondo-Vega María A García-Robles |
| author_facet | Alanis Coca Sergio López Patricio Órdenes Vania Sepúlveda Diego Cuevas Andrés Villarroel Javiera Álvarez-Indo Patricia V. Burgos Estefanía Tarifeño Roberto Elizondo-Vega María A García-Robles |
| author_sort | Alanis Coca |
| collection | DOAJ |
| description | Abstract In the arcuate nucleus of the hypothalamus, tanycyte-neuron interactions regulate glucose homeostasis and feeding behavior. Previously, we reported that monocarboxylate transporters (MCT) 1 and 4 are localized in tanycytes, whereas MCT2 is present in arcuate nucleus neurons, including orexigenic and anorexigenic neurons (POMC). MCT1 and MCT4 inhibition impacts feeding behavior, suggesting that monocarboxylate transfer between tanycytes and neurons influences food intake. Electrophysiological studies have shown that POMC neurons respond to lactate through transport and indirect signaling using astrocytic hydroxycarboxylic acid receptor 1. To investigate the role of MCT2 further, we generated MCT2 knockdown rats and analyzed their feeding behavior. Female Sprague-Dawley rats received bilateral injections in the arcuate nucleus with an adeno-associated virus (AAV) carrying a specific short hairpin RNA to inhibit MCT2 expression, thereby generating neuronal MCT2 knockdown rats. Knockdown efficiency in rat hypothalamic tissue was assessed using real-time PCR, Western Blot, and immunohistochemistry. The acute effect on feeding behavior was evaluated following 24 h of fasting, followed by 24 h of refeeding. In MCT2-knockdown rats, we observed additional inhibition of MCT1, suggesting a potential glial response to increased parenchymal lactate levels. Both macrostructure and microstructure of feeding were evaluated in MCT2-knockdown rats and compared to control AAV-injected rats. MCT2 knockdown led to a significant increase in macrostructural parameters, such as food intake and body weight. These findings underscore the importance of lactate transfer as a mechanism in tanycyte-neuron communication mediated by monocarboxylates. |
| format | Article |
| id | doaj-art-9295b4b722cb4c9997b95e7a99cf463c |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-9295b4b722cb4c9997b95e7a99cf463c2025-08-20T03:05:56ZengNature PortfolioScientific Reports2045-23222025-03-0115111310.1038/s41598-025-90513-2Knocking down the neuronal lactate transporter MCT2 in the arcuate nucleus of female rats increases food intake and body weightAlanis Coca0Sergio López1Patricio Órdenes2Vania Sepúlveda3Diego Cuevas4Andrés Villarroel5Javiera Álvarez-Indo6Patricia V. Burgos7Estefanía Tarifeño8Roberto Elizondo-Vega9María A García-Robles10Laboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de ConcepciónLaboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de ConcepciónLaboratorio de Neuroinmunología, Facultad de Medicina y Ciencia, Universidad San Sebastián, Sede ConcepciónLaboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de ConcepciónLaboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de ConcepciónLaboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de ConcepciónCentro de Biología Celular y Biomedicina, Facultad de Medicina y Ciencia, Universidad San SebastiánCentro de Biología Celular y Biomedicina, Facultad de Medicina y Ciencia, Universidad San SebastiánLaboratorio de Expresión y Regulación Génica, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de ConcepciónLaboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de ConcepciónLaboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de ConcepciónAbstract In the arcuate nucleus of the hypothalamus, tanycyte-neuron interactions regulate glucose homeostasis and feeding behavior. Previously, we reported that monocarboxylate transporters (MCT) 1 and 4 are localized in tanycytes, whereas MCT2 is present in arcuate nucleus neurons, including orexigenic and anorexigenic neurons (POMC). MCT1 and MCT4 inhibition impacts feeding behavior, suggesting that monocarboxylate transfer between tanycytes and neurons influences food intake. Electrophysiological studies have shown that POMC neurons respond to lactate through transport and indirect signaling using astrocytic hydroxycarboxylic acid receptor 1. To investigate the role of MCT2 further, we generated MCT2 knockdown rats and analyzed their feeding behavior. Female Sprague-Dawley rats received bilateral injections in the arcuate nucleus with an adeno-associated virus (AAV) carrying a specific short hairpin RNA to inhibit MCT2 expression, thereby generating neuronal MCT2 knockdown rats. Knockdown efficiency in rat hypothalamic tissue was assessed using real-time PCR, Western Blot, and immunohistochemistry. The acute effect on feeding behavior was evaluated following 24 h of fasting, followed by 24 h of refeeding. In MCT2-knockdown rats, we observed additional inhibition of MCT1, suggesting a potential glial response to increased parenchymal lactate levels. Both macrostructure and microstructure of feeding were evaluated in MCT2-knockdown rats and compared to control AAV-injected rats. MCT2 knockdown led to a significant increase in macrostructural parameters, such as food intake and body weight. These findings underscore the importance of lactate transfer as a mechanism in tanycyte-neuron communication mediated by monocarboxylates.https://doi.org/10.1038/s41598-025-90513-2MCT2Arcuate nucleusFeeding behaviorRatsSatiation |
| spellingShingle | Alanis Coca Sergio López Patricio Órdenes Vania Sepúlveda Diego Cuevas Andrés Villarroel Javiera Álvarez-Indo Patricia V. Burgos Estefanía Tarifeño Roberto Elizondo-Vega María A García-Robles Knocking down the neuronal lactate transporter MCT2 in the arcuate nucleus of female rats increases food intake and body weight Scientific Reports MCT2 Arcuate nucleus Feeding behavior Rats Satiation |
| title | Knocking down the neuronal lactate transporter MCT2 in the arcuate nucleus of female rats increases food intake and body weight |
| title_full | Knocking down the neuronal lactate transporter MCT2 in the arcuate nucleus of female rats increases food intake and body weight |
| title_fullStr | Knocking down the neuronal lactate transporter MCT2 in the arcuate nucleus of female rats increases food intake and body weight |
| title_full_unstemmed | Knocking down the neuronal lactate transporter MCT2 in the arcuate nucleus of female rats increases food intake and body weight |
| title_short | Knocking down the neuronal lactate transporter MCT2 in the arcuate nucleus of female rats increases food intake and body weight |
| title_sort | knocking down the neuronal lactate transporter mct2 in the arcuate nucleus of female rats increases food intake and body weight |
| topic | MCT2 Arcuate nucleus Feeding behavior Rats Satiation |
| url | https://doi.org/10.1038/s41598-025-90513-2 |
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