Obesity has become a worldwide epidemic in western countries, leading to insulin resistance, heart disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). In this respect, the enteroendocrine cells lining the gastrointestinal tract secrete dozens of hormones, upon sensing ingested nutrients, which act in an autocrine, paracrine and endocrine manner to regulate glucose homeostasis and energy balance. Intriguingly, these molecules also possess immunoregulatory properties, which create wide-ranging crosstalk between the secreted peptides, the immune system and different fat tissue depots. Our group aim to decipher the specific role of gut-derived peptides and immune cells-derived molecules, which all play at the interface between the immune system and metabolism. We strive to delineate how the gut-derived peptides affect inflammation and insulin resistance at specific sites, especially fat depots and liver and how they regulate whole body energy homeostasis. We believe that mechanistic insights derived from our research would enable the design of more effective therapies to combat obesity and the metabolic syndrome.