Fructose and metabolic health: governed by hepatic glycogen status?. (21st April 2019)

• Record Type: Journal Article
• Authors: Hengist, Aaron; Koumanov, Francoise; Gonzalez, Javier T.
• Is Part Of: Journal of physiology. Volume 597:Number 14(2019)
• Page Start: 3573
• Page End: 3585
• Publication Date: 2019-04-21
• Subjects: fructose -- liver -- hepatic -- glycogen -- de novo lipogenesis -- metabolism; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP277767
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract: Fructose is a commonly ingested dietary sugar which has been implicated in playing a particularly harmful role in the development of metabolic disease. Fructose is primarily metabolised by the liver in humans, and increases rates of hepatic de novo lipogenesis. Fructose increases hepatic de novo lipogenesis via numerous mechanisms: by altering transcriptional and allosteric regulation, interfering with cellular energy sensing, and disrupting the balance between lipid synthesis and lipid oxidation. Hepatic de novo lipogenesis is also upregulated by the inability to synthesise glycogen, either when storage is inhibited in knock‐down animal models or storage is saturated in glycogen storage disease. Considering that fructose has the capacity to upregulate hepatic glycogen storage, and replenish these stores more readily following glycogen depleting exercise, the idea that hepatic glycogen storage and hepatic de novo lipogenesis are linked is an attractive prospect. We propose that hepatic glycogen stores may be a key factor in determining the metabolic responses to fructose ingestion, and saturation of hepatic glycogen stores could exacerbate the negative metabolic effects of excessive fructose intake. Since physical activity potently modulates glycogen metabolism, this provides a rationale for considering nutrient–physical activity interactions in metabolic health. Abstract : High hepatic glycogen stores resulting from low levels of physical activity and fructose intake may synergistically augment hepatic de novo lipogenesis, whereas low hepatic glycogen stores resulting from high levels of physical activity and no fructose intake may help decrease hepatic de novo lipogenesis. VLDL, very‐low‐density lipoprotein; PDH, pyruvate dehydrogenase; SREBP‐1c, sterol regulatory element binding protein isoform 1c; ChREBP, carbohydrate response element binding protein; ACC, acetyl coenzyme A carboxylase.