RESUMO
d-Serine is abundant in the forebrain and physiologically important for modulating excitatory glutamatergic neurotransmission as a coagonist of synaptic N-methyl-d-aspartate (NMDA) receptor. NMDA signaling has been implicated in the control of food intake. However, the role of d-serine on appetite regulation is unknown. To clarify the effects of d-serine on appetite, we investigated the effect of oral d-serine ingestion on food intake in three different feeding paradigms (one-food access, two-food choice, and refeeding after 24-h fasting) using three different strains of male mice (C57Bl/6J, BKS, and ICR). The effect of d-serine was also tested in leptin signaling-deficient db/db mice and sensory-deafferented (capsaicin-treated) mice. The expression of orexigenic neuropeptides [neuropeptide Y (Npy) and agouti-related protein (Agrp)] in the hypothalamus was compared in fast/refed experiments. Conditioned taste aversion for high-fat diet (HFD) was tested in the d-serine-treated mice. Under the one-food-access paradigm, some of the d-serine-treated mice showed starvation, but not when fed normal chow. HFD feeding with d-serine ingestion did not cause aversion. Under the two-food-choice paradigm, d-serine suppressed the intake of high-preference food but not normal chow. d-Serine also effectively suppressed HFD intake but not normal chow in db/db mice and sensory-deafferented mice. In addition, d-serine suppressed normal chow intake after 24-h fasting despite higher orexigenic gene expression in the hypothalamus. d-Serine failed to suppress HFD intake in the presence of L-701,324, the selective and full antagonist at the glycine-binding site of the NMDA receptor. Therefore, d-serine suppresses the intake of high-preference food through coagonism toward NMDA receptors.
Assuntos
Depressores do Apetite/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/agonistas , Serina/farmacologia , Proteína Relacionada com Agouti/metabolismo , Animais , Comportamento de Escolha , Condicionamento Psicológico , Dieta Hiperlipídica , Regulação para Baixo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Neuropeptídeo Y/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Fármacos do Sistema Sensorial , Fatores de TempoRESUMO
Three months after esophagectomy for esophageal cancer, a 58-year-old man presented with fluid trapped in his upper mediastinum due to chylous leakage from a duplicated left-sided thoracic duct that remained after excision of the main thoracic duct. Classical lymphangiography using lipiodol confirmed the presence of duplicated thoracic ducts. Conservative treatments were not effective, and then we performed ligation of the left-sided thoracic duct with left-sided video-assisted thoracoscopic surgery. Anatomic variations of the thoracic duct can result in chylous leakage after thoracic surgery. Even if the patient has anomaly of the thoracic duct, classical lymphangiography is useful for detecting locations of the thoracic duct precisely, allowing for certain ligation of the duct with video-assisted thoracoscopic surgery.