A newly developed feeder and oxygen measurement system reveals the effects of aging and obesity on the metabolic rate of zebrafish.

Metabolic alterations are relevant for the aging process. Declining metabolic rate with age is a common future of many animals, but it is not well understood how it does so. Here, we used zebrafish as a model for understanding how metabolic changes occur during aging and the interaction between aging and obesity on the metabolic rate. The oxygen consumption rate (OCR) has been used as an index of metabolic processes; however, it is difficult to accurately evaluate OCR with movement being considered because zebrafish need to move freely during the OCR measurement. To measure metabolic rate with high accuracy and efficiency, we developed a method for simultaneously collecting data on sequential oxygen consumption and distance moved by zebrafish using optical dissolved-oxygen sensors and the EthoVision video-tracking system as well as an automatic feeding system for zebrafish whereby obese zebrafish were produced by short-term overfeeding treatment. Using these systems, we examined metabolic changes during aging and overfeeding. First, we used 1- to 22-month-old zebrafish to evaluate changes in metabolism during the aging process. Measurements of body mass and length showed that the growth of the body rarely continued beyond 6 months, at which point zebrafish reach adulthood. Spontaneous swimming activity peaked at approximately 6-10 months and declined thereafter. Metabolic rates at low movement dramatically dropped during the first 4 months and gradually decreased with age after 10 months. These data suggest that metabolic aging becomes evident at approximately 10-14 months and that the metabolic rate (low movement) is useful for the detection of age-related metabolic changes in zebrafish. Second, by short-term overfeeding treatment using the automatic feeding system, we found that overweight is a strong risk factor for the development of metabolic disorders in zebrafish, but there was no interaction between obesity and aging on the metabolic rate. Therefore, our data suggest that the aging-related decline in metabolic-rate may be mostly programmed rather than being affected by energy balance disorder.

Notch signaling regulates the expression of glycolysis-related genes in a context-dependent manner during embryonic development.

Glycolysis, the classic pathway for producing energy, has been known to be involved in neural development. Notch signaling also contributes to neural development and regulation of glycolysis in various tissues. However, the role of Notch signaling in glycolysis-related gene regulation during neural development is poorly understood. Here, we analyzed mRNA expression patterns and levels of glucose transporters (GLUT) as well as rate-limiting enzymes in glycolysis using zebrafish mib1ta52b mutants, in which Notch signaling was deficient at the early embryonic and larval stages. Our results indicated that in neural tissues, Notch signaling positively regulates glut1a and glut3a expression and negatively regulates hk2 expression at the larval stage but may not regulate them during early embryonic stages. Therefore, these results suggest that Notch signaling regulates glycolysis-related gene expression in a context-dependent manner in neural tissues at different developmental stages.