Background: Nutrient excess during obesity can contribute to type 2 diabetes mellitus (T2DM) risk via endoplasmic reticulum (ER) stress within adipose tissue. Investigating ’Superfoods’ such as broccoli that contain nutrients which may be able to combat this disruption is therefore important to potentially reduce the risk of developing T2DM in obesity.
Methods: Differentiated human adipocytes (Chub-S7, n=6) were treated with a broccoli extract (BE; hybrid Brassica oleracea var. italic; 10ng/ml) alone or in combination with tunicamycin (Tun; 750ng/ml), an inducer of ER stress. ER stress genes (ATF4, ATF6 and CHOP) were measured at three time points (24hr, 48hr, 72hr, n=3) using qPCR. ER stress proteins (BiP, P-eIF2α and eIF2α) were measured at 18 time points (0hr - 72hr) using Western Blot.
Results: Tun increased ER stress gene expression 4.5-fold (p<0.001), whilst BE+Tun reduced this expression by up to 64% (p<0.001). Similarly, Tun increased ER stress proteins 9.5-fold (p<0.05), whilst BE+Tun reduced expression by up to 94% (p<0.05). Transcriptomic analysis also highlighted positive significant changes in the mevalonate pathway with the use of BE in treated adipocytes (P<0,05), suggesting a possible mechanism of action.
Conclusion: These studies suggest that BE is able to alleviate ER stress in human adipocytes, possibly via mevalonate pathway activation, thus reducing the risk of subjects developing insulin resistance and T2DM. As such, there is the potential to develop a BE dietary supplement to reduce ER stress and reduce the impact of obesity on T2DM.
A. Murphy: None. G. Barker: None. G. Tripathi: None. P.G. McTernan: None.
Engineering and Physical Sciences Research Council