Roles of leptin receptor-expressing neurons in body weight regulation

Abstract

Obesity is a growing health problem concerning much of the human civilization. Fundamental research into the underlying mechanisms of body weight regulation can open new paths that will lead to a larger array of treatment options. Leptin is a hormone that plays a crucial role in body weight regulation. It is known for reducing food intake and increasing energy expenditure via leptin receptor (LepR) signalling in the brain. Although leptin is known for reducing food intake, this thesis describes the variable effects of leptin on feeding in mice: after leptin injections, some mice decreased feeding, while others increased feeding. Even more, the feeding effect of leptin predicted how much weight a mouse gained on a high caloric diet: mice that increased feeding with leptin, gained more weight and vice versa. This thesis further addresses how LepR-neurons (neurons that are responsive to leptin) of different brain areas influence aspects of body weight regulation: food consumption, motivation to work for food reward, locomotor activity and body temperature. To do so, we used chemogenetics, which is a technique with which we can temporarily activate LepR-neurons of a certain brain area and examine the effect of this activation on behavioural tasks. We found that the four studied LepR-containing brain areas differently affect aspects of body weight regulation. This thesis sheds more light on how leptin and LepR-neurons influence body weight. With this we hope to contribute to exciting new discoveries that will aid in the reduction of the obesity pandemic.