Ulrike Liisberg:
Dietary protein source and cyclooxygenase-inhibition influence development of diet-induced obesity, glucose homeostasis and brown adipose tissue

Date: 12-06-2015    Supervisor: Karsten Kristiansen & Lise Madsen

The prevalence of obesity and associated diseases, such as Type 2 diabetes, cardiovascular disease and non-alcoholic fatty liver disease, are accelerating worldwide and require urgent attention. Many of the obesity-related morbidities are likely to originate from a state of chronic low-grade inflammation accompanying the increasing adipose mass. In order to investigate the relationship between obesity, inflammation and insulin resistance, we ran an experiment feeding mice a high fat/high sucrose diet supplemented with the antiinflammatory cyclooxygenase-inhibitor, indomethacin. We saw that indomethacin prevented diet-induced obesity and glucose intolerance, but not insulin resistance.

The development of obesity is largely dependent on an imbalance in energy intake relative to expenditure. Thus, strategies that influence energy utilization is of relevance in anti-obesity treatment. High protein diets, in general, have shown promise in reducing and maintaining bodyweight, but less is established when it comes to different protein sources. Here, we present results from experiments investigating the effect of various protein sources given to mice in different dietary compositions. We report striking differences between various protein sources in relation to the development of obesity, insulin resistance and hepatic lipid accumulation. Casein protein, despite being the regular protein source used in experimental diets for rodents, seems to provide strong protection against obesity. This was, at least in part, due to the maintenance of a classical interscapular brown depot with high expression of UCP1 in these mice. Conversely, proteins from terrestrial animals promoted gain of adipose mass, hyperinsulinemia and impaired glucose tolerance. In addition, when combined in a typical Western diet, the lean protein source, pork, seemed to promote obesity. However, this was attenuated when pork was exchanged for cod. Reduced feed-intake in the cod-fed mice could provide some explanation for this, but, other mechanisms, potentially involving endocannabinoids, may play a role. The small amount of endogenous n-3 PUFAs present in phospholipid fractions of the cod fillets was reflected in the red-blood cells and the livers of the mice. This subsequently caused an altered endocannabinoid tone in the mice. In addition to amino acids, changing protein sources also alters fat, which may affect the consumer. This were clearly demonstrated when the casein in a Western diet was exchanged with salmon fillets from salmon fed fish oil or different vegetable oils. Both the diets and the red blood cells of the mice reflected the fatty acid composition of the fillets, which had a great impact on their insulin sensitivity and hepatic lipid accumulation.