Exploring food concepts for the prevention of type 2 diabetes

Abstract: There is currently a dramatic and global increase in obesity, type 2 diabetes (T2D) and associated metabolic disorders. T2D can be delayed or prevented in individuals at risk and identifying and developing new food concepts for the prevention of obesity and T2D is of utmost importance. This thesis describes our work on exploring new food concepts for the prevention of T2D. We have used 3T3-L1 adipocytes, and C57BL/6J mice as experimental models and we have also carried out an intervention study in humans. We found that whole grain rye is better at preventing body weight gain than whole grain wheat in C57BL/6J mice fed a low-fat diet. The lower body weight reflected reduced adiposity and smaller adipocyte size and was accompanied by lower levels of circulating leptin. The reduction in adiposity could not be explained by alterations in the expression of genes involved in adipogenesis or lipogenesis. Furthermore, whole grain rye lowered plasma cholesterol and triacylglycerol, unlike whole grain wheat. Whole grain rye contains several bioactive components, including alkylresorcinols (ARs). We showed that ARs isolated from rye bran suppress catecholamine-stimulated lipolysis in 3T3-L1 adipocytes. Obesity and insulin-resistant states are often characterised by a dysfunctional adipose tissue with insufficient trapping of fatty acids. Our results suggest that intake of ARs could lead to lower levels of circulating fatty acids in vivo which could have beneficial effects in relation to insulin resistance. Furthermore, we showed that a large dose of rose hip induces several beneficial metabolic effects in mice, including anti-obesity effects, reduced hepatic lipid accumulation, reduced plasma cholesterol and improved glucose tolerance. The reduced hepatic lipid accumulation was accompanied by lowered plasma alanine aminotransferase levels, and was associated with a down-regulation of the hepatic lipogenic programme. However, lower doses of rose hip failed to induce anti-obesity effects in obese non-diabetic humans. Also, no effect of rose hip on glucose tolerance was observed in humans, probably due to the lack of effect on adiposity. However, rose hip induced a reduction in total plasma cholesterol as well as in the LDL to HDL ratio in both mice and humans. The beneficial effects of rose hip could be attributed to increased faecal excretion of both triacylglycerol and cholesterol.

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