Even Fjære:
Effects of macronutrient composition and cyclooxygenase-inhibition on diet-induced obesity, low grade inflammation and glucose homeostasis

Date: 31-10-2012    Supervisor: Karsten Kristiansen & Lise Madsen

Background: Obesity and its related metabolic complications are an increasing problem worldwide. A high fat diet in combination with sucrose has been shown to induce obesity and development of glucose intolerance and insulin resistance in rodents. C57BL/6J mice were fed high fat diets with sucrose- or protein based background, and supplemented with either corn- or fish oil. These experiments were conducted to determine whether macronutrient composition and type of dietary fat can modulate diet-induced obesity, and associated metabolic consequences. The use of non-steroidal anti-inflammatory drugs is escalating, and in view of the increased consumption of obesogenic diets with high levels of dietary carbohydrates and fat, the metabolic consequences of cyclooxygenase-inhibition warrants investigation.

Results: High fat/high sucrose diets increased obesity development and expression of macrophage infiltration markers in the adipose tissue. By increasing the amount of dietary protein, at the expanse of sucrose, the obesogenic effect of the HF diet was prevented. The reduced obesogenic effect of the high fat/high protein diet was associated with increased expression of genes related to hepatic gluconeogenesis and ureagenesis, in addition to genes related to thermogenesis. Fish oil enriched diets with polyunsaturated omega-3 fatty acids, are shown to prevent diet-induced obesity, however, this effect was blunted with increased sucrose content in the diet. The obesogenic high fat/high diet in combination with indomethacin, a nonselective cyclooxygenase cyclooxygenase-inhibitor, reduces energy efficiency and fat mass in C57BL/6J mice. Despite prevention of obesity development, indomethacin treatment was associated with hyperglycemia and reduced glucose tolerance. Body weight was not affected when indomethacin was combined with a low fat diet. This further highlights the importance of the background diet and macronutrient composition of experimental diets.

Conclusions: In summary, our results demonstrate that the composition of background diet modulates the obesogenic effect of the high fat diet. The obesogenic effect of a high fat/ high sucrose diet can also be prevented with inclusion of indomethacin in the diet.