The dietary sugars that most strongly promote hepatic de novo lipogenesis are fructose and sugars containing high proportions of fructose, notably sucrose and high-fructose corn syrup. Metabolic and clinical research identifies fructose as more lipogenic than glucose because of the way the liver metabolizes it and because of evidence from controlled feeding studies.
Mechanism of increased lipogenesis
Fructose is taken up and phosphorylated in the liver by fructokinase, a step that bypasses the key regulatory enzyme phosphofructokinase that controls glycolytic flux for glucose. Kevin G. Frayn University of Oxford has described how this hepatic routing of fructose yields triose phosphates that are readily converted to acetyl-CoA, supplying substrate for de novo lipogenesis and for synthesis of triglycerides. This biochemical characteristic makes fructose intrinsically more likely to drive hepatic fat synthesis than an equivalent amount of glucose under many conditions.
Human feeding studies and clinical evidence
Clinical trials led by Kimber L. Stanhope University of California Davis and Peter J. Havel University of California Davis compared beverages sweetened with fructose to those sweetened with glucose and found that fructose increased postprandial and fasting rates of hepatic de novo lipogenesis, raised hepatic lipid content, and promoted increases in visceral fat and dyslipidemia relative to glucose. George A. Bray Pennington Biomedical Research Center and other investigators have linked consumption of fructose-containing sweeteners in sugar-sweetened beverages to higher risks of weight gain and metabolic disturbances in population studies. Robert H. Lustig University of California San Francisco has emphasized how patterns of processed-food availability amplify these metabolic effects at a population level.
The relevance extends beyond biochemistry to public health and culture. Populations with high intake of processed foods and sugar-sweetened beverages, often driven by economic and marketing forces, face greater exposure to fructose-rich sugars, which contributes to the rising prevalence of nonalcoholic fatty liver disease and cardiometabolic disorders. Individual susceptibility, overall diet composition, and total caloric balance modify risk, but the weight of mechanistic and human trial evidence supports prioritizing reductions in fructose and fructose-containing sweeteners to lower hepatic lipogenesis and related harms.