Short term consumption of a Western diet upregulates the O‐linked‐β‐N‐acetylglucosamine (O‐GlcNAc) pathway in young mouse hearts

Diets high in sugar and saturated fat (“Western” diets) contribute to the incidence of metabolic syndrome and cardiovascular disease (CVD). The post‐translational attachment of an O‐linked‐β‐N‐acetylglucosamine (O‐GlcNAc) sugar on serine and threonine residues of cytoplasmic and nuclear proteins is an important mediator of signal transduction; the addition of O‐GlcNAc residues to proteins is catalyzed by O‐GlcNAc transferase (OGT). In order to determine the effects of ingesting a Western diet on the O‐GlcNAc pathway, we fed young (5 week old) C57BL/6 male mice either a control (n=8) or Western diet (n=8) for 14 days and examined O‐GlcNAc levels in nuclear and cytoplasmic proteins in the heart. Weight gain, fasting blood glucose, and heart wet weight were significantly higher in the Western diet group (P<0.05). O‐GlcNAc protein was higher in cytosolic and nuclear fractions of Western‐fed hearts but this was not statistically significant (P=0.19 and P=0.12, respectively). We also found a significant increase in OGT protein in both the nuclear and cytosolic fractions in Western diet‐fed hearts (P<0.05). In summary, we have shown, for the first time, short term consumption of a Western diet upregulates the O‐GlcNAc pathway in young mouse hearts. These data suggest that increased O‐GlcNAc may be one mechanism that promotes the development of CVD with consumption of a Western diet.