Fructuoso Marta, Espinosa-Carrasco Jose, Erb Ionas, Notredame Cedric, Dierssen Mara
Cellular and Systems Neurobiology, Systems Biology Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, Barcelona 08003, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Bio Protoc. 2019 Jul 20;9(14):e3308. doi: 10.21769/BioProtoc.3308.
Obesity is an important health problem with a strong environmental component that is acquiring pandemic proportion. The high availability of caloric dense foods promotes overeating potentially causing obesity. Animal models are key to validate novel therapeutic strategies, but researchers must carefully select the appropriate model to draw the right conclusions. Obesity is defined by an increased body mass index greater than 30 and characterized by an excess of adipose tissue. However, the regulation of food intake involves a close interrelationship between homeostatic and non-homeostatic factors. Studies in animal models have shown that intermittent access to sweetened or calorie-dense foods induces changes in feeding behavior. However, these studies are focused mainly on the final outcome (obesity) rather than on the primary dysfunction underlying the overeating of palatable foods. We describe a protocol to study overeating in mice using diet-induced obesity (DIO). This method can be applied to free choice between palatable food and a standard rodent chow or to forced intake of calorie-dense and/or palatable diets. Exposure to such diets is sufficient to promote changes in meal pattern that we register and analyze during the period of weight gain allowing the longitudinal characterization of feeding behavior in mice. Abnormal eating behaviors such as binge eating or snacking, behavioral alterations commonly observed in obese humans, can be detected using our protocol. In the free-choice procedure, mice develop a preference for the rewarding palatable food showing the reinforcing effect of this diet. Compulsive components of feeding are reflected by maintenance of feeding despite an adverse bitter taste caused by adulteration with quinine and by the negligence of standard chow when access to palatable food is ceased or temporally limited. Our strategy also enables to identify compulsive overeating in mice under a high-caloric regime by using limited food access and finally, we propose complementary behavioral tests to confirm the non-homeostatic food-taking triggered by these foods. Finally, we describe how to computationally explore large longitudinal behavioral datasets.
肥胖是一个重要的健康问题，其强大的环境因素使其呈现大流行态势。高热量食物的高可得性促使人们过度进食，进而可能导致肥胖。动物模型是验证新型治疗策略的关键，但研究人员必须谨慎选择合适的模型以得出正确结论。肥胖的定义是体重指数（BMI）大于30且以脂肪组织过多为特征。然而，食物摄入的调节涉及稳态和非稳态因素之间的密切相互关系。动物模型研究表明，间歇性接触甜味或高热量食物会导致进食行为发生变化。然而，这些研究主要集中在最终结果（肥胖）上，而非美味食物过度进食背后的主要功能障碍。我们描述了一种使用饮食诱导肥胖（DIO）来研究小鼠过度进食的方案。该方法可应用于在美味食物和标准啮齿动物饲料之间自由选择，或强制摄入高热量和/或美味饮食。接触此类饮食足以促进进食模式的变化，我们在体重增加期间记录并分析这些变化，从而对小鼠的进食行为进行纵向表征。使用我们的方案可以检测到肥胖人类中常见的异常进食行为，如暴饮暴食或吃零食等行为改变。在自由选择程序中，小鼠会对美味的奖励性食物产生偏好，显示出这种饮食的强化作用。喂食的强迫性成分体现在，尽管用奎宁掺假会产生不良苦味，但仍持续进食，以及在停止或暂时限制获取美味食物时忽视标准饲料。我们的策略还能够通过限制食物获取来识别高热量饮食模式下小鼠的强迫性过度进食，最后，我们提出补充行为测试以确认这些食物引发的非稳态摄食。最后，我们描述了如何通过计算探索大型纵向行为数据集。
