Collective and experimental research project for master's students on the pathophysiology of obesity.

We describe here a collective and experimental research project-based learning (ERPBL) for master's students that can be used to illustrate some basic concepts on glucose/lipid homeostasis and renal function around a topical issue. The primary objective of this ERPBL was to strengthen students' knowledge and understanding of physiology and pathophysiology. The secondary objectives were to help students to develop technical/practical abilities and acquire transversal skills with real-world connections. Obesity is a worldwide public health problem that increases the risk for developing type 2 diabetes and nephropathies. To study the impact of western dietary habits, students evaluated the effects of a diet enriched with fat and cola [high-fat and cola diet (HFCD)] on metabolism and renal function in mice. Students mainly worked in tandem to prepare and perform experiments, but also collectively to compile, analyze, and discuss data. Students showed that HFCD-fed mice 1) developed obesity; 2) exhibited glucose homeostasis impairments associated to ectopic fat storage; and 3) displayed reduced glomerular filtration. The educational benefit of the program was estimated using three evaluation metrics: a conventional multicriteria assessment by teachers, a pre-/posttest, and a self-evaluation questionnaire. They showed that the current approach successfully strengthened scientific student knowledge and understanding of physiology/pathophysiology. In addition, it helped students develop new skills, such as technical and transversal skills. We concluded that this ERPBL dealing with the pathophysiology of obesity was strongly beneficial for master's students, thereby appearing as an efficient and performing educational tool.

Hypothalamic reactive oxygen species are required for insulin-induced food intake inhibition: an NADPH oxidase-dependent mechanism.

OBJECTIVE: Insulin plays an important role in the hypothalamic control of energy balance, especially by reducing food intake. Emerging data point to a pivotal role of reactive oxygen species (ROS) in energy homeostasis regulation, but their involvement in the anorexigenic effect of insulin is unknown. Furthermore, ROS signal derived from NADPH oxidase activation is required for physiological insulin effects in peripheral cells. In this study, we investigated the involvement of hypothalamic ROS and NADPH oxidase in the feeding behavior regulation by insulin. RESEARCH DESIGN AND METHODS: We first measured hypothalamic ROS levels and food intake after acute intracerebroventricular injection of insulin. Second, effect of pretreatment with a ROS scavenger or an NADPH oxidase inhibitor was evaluated. Third, we examined the consequences of two nutritional conditions of central insulin unresponsiveness (fasting or short-term high-fat diet) on the ability of insulin to modify ROS level and food intake. RESULTS: In normal chow-fed mice, insulin inhibited food intake. At the same dose, insulin rapidly and transiently increased hypothalamic ROS levels by 36%. The pharmacological suppression of this insulin-stimulated ROS elevation, either by antioxidant or by an NADPH oxidase inhibitor, abolished the anorexigenic effect of insulin. Finally, in fasted and short-term high-fat diet-fed mice, insulin did not promote elevation of ROS level and food intake inhibition, likely because of an increase in hypothalamic diet-induced antioxidant defense systems. CONCLUSIONS: A hypothalamic ROS increase through NADPH oxidase is required for the anorexigenic effect of insulin.