Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2019:12 821–826
Brandon H. Mai and Liang-Jun Yan.
Objective
- This review focuses the discussion on the hepatic manifestations of high fructose-implicated liver metabolic disorders such as insulin resistance, obesity due to enhanced lipogenesis, non-alcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and type 2 diabetes.
Background
- The increased consumption of fructose in the average diet through sweeteners such as high-fructose corn syrup (HFCS) and sucrose has resulted in negative outcomes in society through producing a considerable economic and medical burden on our healthcare system.
- Ingestion of fructose chronically has contributed to multiple health consequences, such as insulin resistance, obesity, liver disorders, and diabetes.
- Fructose metabolism starts with fructose phosphorylation by fructose kinase in the liver, and this process is not feedback regulated. Therefore, ingestion of high fructose can deplete ATP, increase uric acid production, and increase nucleotide turnover.
Methods
- No methodology was reported in this review.
Findings
- Studies have shown that hyperuricemia is associated with both NAFLD and NASH. Among the potential causes found, impaired beta oxidation of fatty acids in the liver and enhanced de novo lipogenesis are thought to contribute most towards this outcome.
- Fructokinase C has been especially noted to facilitate this fat accumulation in the liver via uric acid generation, a decrease of ATP, and increased nucleotide turnover.
- Still, there are contradictory findings in some studies that suggest fructose consumed over shorter durations or in lower doses may not express these relationships. Additionally, it should be noted that there are likely many other factors that contribute towards the magnitude of the effects of fructose which should be taken into consideration, such as physical inactivity and other dietary components, as well as gestation and lactation periods which lead to deep metabolic changes in mothers and in their progeny via metabolic early programming.
Conclusions
- Further research with larger clinical trials that examine the effects of lowering HCFS and sugar consumption as well as uric acid levels is warranted to confirm the impact of fructose on health.
- Further investigation to gain a better understanding of inhibiting or disrupting fructose metabolism in the liver and its effects on specific metabolic regulators may potentially lead to innovative solutions towards chronic liver disorder prevention and treatment that can change the landscape of healthcare.