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Sex‐specific metabolic changes induced by high fructose corn syrup during adolescence: novel evidence from metabolomic and microbiome analyses in mice

Overconsumption of high fructose corn syrup (HFCS) in the form of an added sweetener in beverages has been strongly linked to the development of metabolic diseases, including obesity and non-alcoholic fatty liver diseases (NAFLD) (Pinnick & Hodson, 2019). Although high dietary sugar intake in general shows unfavourable metabolic outcomes, fructose in particular is gaining a worse reputation over time. Increasing evidence reveals that high fructose consumption contributes to increased body fat, dyslipidaemia, insulin resistance, increased oxidative stress and inflammation, all of which are key features of metabolic disorders (Pinnick & Hodson, 2019). More importantly, adolescents are prone to be affected by high fructose intake as they are in a vulnerable developmental window but also the major consumers of HFCS-added beverages (Pinnick & Hodson, 2019). In addition, changes in sex hormones with the onset of puberty may lead to sex-specific effects in the context of fructose overconsumption (Patton et al. 2006). Therefore, sex and age are the two key variables in fructose induced metabolic changes. However, few studies have focused on sex differences linked to high fructose intake in specific age groups, highlighting the need for future investigations to fill in the gaps. In a recent issue in The Journal of Physiology, Bhat et al. (2021) explored the effects of HFCS consumption in both male and female mice during adolescence (3–6 weeks old), and further examined if any of the outcomes persisted into adulthood (30 weeks old). At 3 weeks old, C57Bl/6J mice were fed with a standard chow diet supplemented with either water or 50% HFCS in water for 3 weeks. To examine the long-lasting effects, the mice were kept on a standard chow diet with water until 30 weeks old. Measurements from metabolic analyses, hepatic metabolomic profiling and gut microbiome analyses revealed that: (1) HFCS exposure during adolescence increased body weight, fat mass, glucose intolerance and hepatic fat in a sex-specific manner; (2) significant changes in hepatic metabolites and gut microbiome profiles were observed after 3 weeks of HFCS exposure, which differed with sex; (3) some of the changes lasted into adulthood long after HFCS exposure ceased.