Challenging metabolic tissues with fructose: tissue-specific and sex-specific responses

Excessive consumption of free sugars (which typically includes a composite of glucose and fructose) is associated with an increased risk of developing chronic metabolic diseases including obesity, non-alcoholic fatty liver disease (NAFLD), type 2 diabetes and cardiovascular disease. Determining the utilisation, storage and fate of dietary sugars in metabolically relevant tissues is fundamental to understanding their contribution to metabolic disease risk. To date, the study of fructose metabolism has primarily focused on the liver, where it has been implicated in impaired insulin sensitivity, increased fat accumulation and dyslipidaemia. Yet we still have only a limited understanding of the mechanisms by which consumption of fructose, as part of a mixed meal, may alter hepatic fatty acid synthesis and partitioning. Moreover, surprisingly little is known about the metabolism of fructose within other organs, specifically subcutaneous adipose tissue, which is the largest metabolically active organ in the human body and is consistently exposed to nutrient fluxes. This review summarises what is known about fructose metabolism in the liver and adipose tissue and examines evidence for tissue-specific and sex-specific responses to fructose.