Niels Banhos Danneskiold-Samsøe:
Interplay between diet, gut microbiota, immune cells and energy metabolism in obesity development

Date: 31-03-2016    Supervisor: Karsten Kristiansen

Obesity and associated metabolic disorders such as type 2 diabetes are major causes of morbidity and mortality globally. A major contributor to development of the obesity pandemic has been the increasing intake of energy dense diets, consisting of dietary fats combined with high-glycemic carbohydrates such as refined grains and sugars. The lack of sufficient therapeutic options for obesity, and the inability of most individuals to reduce energy intake or increase expenditure highlight the importance of understanding its underlying biological mechanisms.

Obesity is associated with low-grade inflammation contributing to development of insulin resistance and obesity. Dietary habits are linked to changes in the gut bacterial composition (gut microbiota) which is central to host inflammatory response and metabolism in the development of obesity and associated metabolic disorders. Thus, detailed investigation of the interactions between the diet, gut microbiota and development of inflammation is necessary to understand development of obesity. For this, it is important to understand the regulation of the local immune system of fat and other tissues important for regulation of systemic metabolism.

To investigate the inflammatory responses in fat and in the liver in obesity, and its interactions with the gut microbiota and diet, we carried out a series of experiments in mice on high-fat diets. Our results show that dietary addition of gliadin (a component in gluten) to a high-fat diet can modulate glucose and lipid metabolism, and is associated with alterations in the gut microbiota and immune cell profile in adipose tissue. We also demonstrate that moderate weight gain on a high-fat/high-sucrose diet based on safflower oil, one of the most rich sources of n-6 polyunsaturated fatty acids can results in glucose intolerance without inflammatory changes in visceral fat or the liver, but with changes to the gut microbiota. Finally we find that fat cell specific activity of cyclooxygenase-2, an enzyme important for metabolism of fat, decreases body fat mass and increases insulin sensitivity associated with an improved inflammatory profile in the adipose tissue.