Highlights
•It is debated whether fructose drives the metabolic syndrome or non-alcoholic fatty liver disease
•Fructose in a liquid form as sugar sweetened beverages may impact liver metabolism
•Result: consumption of beverages containing fructose or sucrose increase hepatic lipogenesis
•Increased hepatic lipogenic activity may promote long term metabolic perturbations
Abstract

Background & aims
Excessive fructose intake associates with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. Whether fructose-specific effects on lipid metabolism in healthy men exist independently from overfeeding needs clarification.

Methods
94 subjects were studied in this double-blind, randomized trial. They were assigned to daily consumption of sugar-sweetened beverages (SSB) containing moderate amounts of fructose, sucrose (fructose-glucose disaccharide) or glucose (80g/day) in addition to their usual diet or SSB abstinence (control group) for seven weeks. De novo fatty acid (FA) and triglyceride (TAG) synthesis, lipolysis and plasma free FA (FFA) oxidation were assessed by tracer methodology.

Results
Daily intake of beverages sweetened with free fructose and fructose combined with glucose (sucrose) increased basal fractional secretion rates (FSR) of newly synthesized FA by the liver 2-fold compared to control (median FSR %/day: sucrose 20.8 (p=0.0015); fructose 19.7 (p=0.013); control 9.1). Conversely, the same amounts of glucose did not change FSR (median of FSR %/day 11.0 (ns)). Fructose intake did not change basal secretion of newly synthesized VLDL-TAG. It did neither alter rates of peripheral lipolysis nor total FA and plasma FFA oxidation. Total energy intake was similar across groups with SSB intake and controls.

Conclusions
Regular consumption of both fructose and sucrose sweetened beverages in moderate doses associated with stable caloric intake increases hepatic FA synthesis even in a basal state, whereas this effect is not observed after consumption of glucose. These findings support the hypothesis of an adaptative response of the liver to regular fructose exposure, i. e. habitual SSB consumption.

Lay summary
This study investigated the metabolic effects of daily sugar-sweetened beverage consumption for several weeks in healthy lean men. It revealed that beverages sweetened with the sugars fructose and sucrose (glucose and fructose combined), but not glucose, increase the ability of the liver to produce lipids. This change may pave the way for further unfavorable effects on metabolic health.