[Dapagliflozin, a Sodium-Glucose Co-transporter-2 Inhibitor, Acutely Reduces Energy Expenditure in Brown Adipose Tissue via Neural Signals in Mice].

　Selective sodium glucose transporter-2 inhibitor (SGLT2i) treatment promotes urinary glucose excretion, thereby reducing blood glucose as well as body weight. However, only limited body weight reductions are achieved with SGLT2i administration. Hyperphagia is reportedly one of the causes of this limited weight loss. However, the effects of SGLT2i on systemic energy expenditure have not been fully elucidated. We investigated the acute effects of dapagliflozin, an SGLT2i, on systemic energy expenditure in mice. Eighteen hours after dapagliflozin administration, oxygen consumption and brown adipose tissue (BAT) expression of ucp1, a thermogenesis-related gene, were significantly decreased as compared with those after vehicle administration. In addition, dapagliflozin significantly suppressed norepinephrine (NE) turnover in BAT and c-fos expression in the rostral raphe pallidus nucleus (rRPa), which contains the sympathetic premotor neurons responsible for thermogenesis. These findings indicate that the dapagliflozin-mediated acute decrease in energy expenditure involves a reduction in BAT thermogenesis via decreased sympathetic nerve activity from the rRPa. Furthermore, common hepatic branch vagotomy abolished the reductions in ucp1 expression, NE contents in BAT, and c-fos expression in the rRPa. In addition, alterations in hepatic carbohydrate metabolism, such as decreases in glycogen contents and upregulation of phosphoenolpyruvate carboxykinase, occurred prior to the suppression of BAT thermogenesis, e.g., 6 h after dapagliflozin treatment. Collectively, these results suggest that SGLT2i acutely suppresses energy expenditure in BAT via regulation of an interorgan neural network consisting of the common hepatic vagal branch and sympathetic nerves.

Dapagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, Acutely Reduces Energy Expenditure in BAT via Neural Signals in Mice.

Selective sodium glucose cotransporter-2 inhibitor (SGLT2i) treatment promotes urinary glucose excretion, thereby reducing blood glucose as well as body weight. However, only limited body weight reductions are achieved with SGLT2i treatment. Hyperphagia is reportedly one of the causes of this limited weight loss. However, the effects of SGLT2i treatment on systemic energy expenditure have not been fully elucidated. Herein, we investigated the acute effects of dapagliflozin, a SGLT2i, on systemic energy expenditure in mice. Eighteen hours after dapagliflozin treatment oxygen consumption and brown adipose tissue (BAT) expression of ucp1, a thermogenesis-related gene, were significantly decreased as compared to those after vehicle treatment. In addition, dapagliflozin significantly suppressed norepinephrine (NE) turnover in BAT and c-fos expression in the rostral raphe pallidus nucleus (rRPa) which contains the sympathetic premotor neurons responsible for thermogenesis. These findings indicate that the dapagliflozin-mediated acute decrease in energy expenditure involves a reduction in BAT thermogenesis via decreased sympathetic nerve activity from the rRPa. Furthermore, common hepatic branch vagotomy abolished the reductions in ucp1 expression and NE contents in BAT and c-fos expression in the rRPa. In addition, alterations in hepatic carbohydrate metabolism, such as decreases in glycogen contents and upregulation of phosphoenolpyruvate carboxykinase, manifested prior to the suppression of BAT thermogenesis, e.g. 6 hours after dapagliflozin treatment. Collectively, these results suggest that SGLT2i treatment acutely suppresses energy expenditure in BAT via regulation of an inter-organ neural network consisting of the common hepatic vagal branch and sympathetic nerves.

Life concerns of elderly people living at home determined as by Community General Support Center staff: implications for organizing a more effective integrated community care system. The Kurihara Project.

BACKGROUND: In Japan, the integrated community care system aims to enable people to continue to live in their homes. Based on the concept, one of the activities of a Community General Support Center (CGSC) is to provide preventive intervention based on a Community Support Program. Currently, a Basic Checklist (BC) is sent to elderly people to identify persons appropriate for a Secondary Prevention Program. METHODS: To find people who had not responded to the BC, CGSC staff evaluated the files of 592 subjects who had participated in the Kurihara Project to identify activities they cannot do that they did in the past, decreased activity levels at home, loss of interaction with people other than their family, and the need for medical interventions. This information was classified, when applicable, into the following categories: (A) 'no life concerns'; (B) 'undecided'; and (C) 'life concerns'. The relationships between these classifications and clinical information, certified need for long-term care, and items on the BC were examined. RESULTS: The numbers of subjects in categories A, B, and C were 291, 42, and 186, respectively. Life concerns were related to scores on the Clinical Dementia Rating, global cognitive function, depressive state, and apathy. Most items on the BC were not associated with classification into category C, but ≥25% of the subjects had life concerns related to these items. DISCUSSION: Assessment of life concerns by the CGSC staff has clinical validity. The results suggest that there are people who do not respond to the checklist or apply for Long-Term Care Insurance, meaning that they 'hide' in the community, probably due to apathy or depressive state. To organize a more effective integrated community care system, the CGSC staff should focus mainly on preventive care.