Inhibition of Hypothalamic MCT4 and MCT1–MCT4 Expressions Affects Food Intake and Alters Orexigenic and Anorexigenic Neuropeptide Expressions

• Published in: Molecular neurobiology 2020-02, Vol.57 (2), p.896-909
• Main Authors: Elizondo-Vega, Roberto, Oyarce, Karina, Salgado, Magdiel, Barahona, María José, Recabal, Antonia, Ordenes, Patricio, López, Sergio, Pincheira, Roxana, Luz-Crawford, Patricia, García-Robles, María Angeles
• Format: Article
• Language: English
• Subjects: Animal behavior; Animals; Arcuate nucleus; Biomedical and Life Sciences; Biomedicine; Cell Biology; Energy balance; Feeding; Feeding behavior; Food intake; Ghrelin; Glial cells; Glucose; Hypothalamus; Leptin; Neurobiology; Neurology; Neurons; Neuropeptides; Neurosciences; Satiety; Signal transduction; Tanycytes; Ventricle; Ventricles (cerebral)
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-019-01776-6

Feeding behavior regulation is a complex process, which depends on the central integration of different signals, such as glucose, leptin, and ghrelin. Recent studies have shown that glial cells known as tanycytes that border the basal third ventricle (3V) detect glucose and then use glucose-derived signaling to inform energy status to arcuate nucleus (ARC) neurons to regulate feeding behavior. Monocarboxylate transporters (MCT) 1 and MCT4 are localized in the cellular processes of tanycytes, which could facilitate monocarboxylate release to orexigenic and anorexigenic neurons. We hypothesize that MCT1 and MCT4 inhibitions could alter the metabolic communication between tanycytes and ARC neurons, affecting feeding behavior. We have previously shown that MCT1 knockdown rats eat more and exhibit altered satiety parameters. Here, we generate MCT4 knockdown rats and MCT1–MCT4 double knockdown rats using adenovirus-mediated transduction of a shRNA into the 3V. Feeding behavior was evaluated in MCT4 and double knockdown animals, and neuropeptide expression in response to intracerebroventricular glucose administration was measured. MCT4 inhibition produced a decrease in food intake, contrary to double knockdown. MCT4 inhibition was accompanied by a decrease in eating rate and mean meal size and an increase in mean meal duration, parameters that are not changed in the double knockdown animals with exception of eating rate. Finally, we observed a loss in glucose regulation of orexigenic neuropeptides and abnormal expression of anorexigenic neuropeptides in response to fasting when these transporters are inhibited. Taken together, these results indicate that MCT1 and MCT4 expressions in tanycytes play a role in feeding behavior regulation.