title: Fructose: metabolic, hedonic, and societal parallels with ethanol.
abstract: Rates of fructose consumption continue to rise nationwide and have been linked to rising rates of obesity, type 2 diabetes, and metabolic syndrome. Because obesity has been equated with addiction, and because of their evolutionary commonalities, we chose to examine the metabolic, hedonic, and societal similarities between fructose and its fermentation byproduct ethanol. Elucidation of fructose metabolism in liver and fructose action in brain demonstrate three parallelisms with ethanol. First, hepatic fructose metabolism is similar to ethanol, as they both serve as substrates for de novo lipogenesis, and in the process both promote hepatic insulin resistance, dyslipidemia, and hepatic steatosis. Second, fructosylation of proteins with resultant superoxide formation can result in hepatic inflammation similar to acetaldehyde, an intermediary metabolite of ethanol. Lastly, by stimulating the "hedonic pathway" of the brain both directly and indirectly, fructose creates habituation, and possibly dependence; also paralleling ethanol. Thus, fructose induces alterations in both hepatic metabolism and central nervous system energy signaling, leading to a "vicious cycle" of excessive consumption and disease consistent with metabolic syndrome. On a societal level, the treatment of fructose as a commodity exhibits market similarities to ethanol. Analogous to ethanol, societal efforts to reduce fructose consumption will likely be necessary to combat the obesity epidemic.
authors.affiliation: Division of Endocrinology, University of California, San Francisco, CA 94143-0434, USA. rlustig@peds.ucsf.edu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lustig
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D013549:Sweetening Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D008055:Lipids; D013549:Sweetening Agents; D005632:Fructose; D000431:Ethanol