title: The Sweet Path to Metabolic Demise: Fructose and Lipid Synthesis.
abstract: Epidemiological studies link fructose consumption with metabolic disease, an association attributable in part to fructose-mediated lipogenesis. The mechanisms governing fructose-induced lipogenesis and disease remain debated. Acutely, fructose increases de novo lipogenesis through the efficient and uninhibited action of ketohexokinase and aldolase B which yields substrates for fatty-acid synthesis. Chronic fructose consumption further enhances the capacity for hepatic fructose metabolism by activating several key transcription factors (i.e., SREBP1c and ChREBP) which augment the expression of lipogenic enzymes, increasing lipogenesis and further compounding hypertriglyceridemia and hepatic steatosis. Hepatic insulin resistance develops from diacylglycerol-PKCɛ-mediated impairment of insulin signaling and possibly additional mechanisms. Initiatives that decrease fructose consumption and therapies that block fructose-mediated lipogenesis will be necessary to avert future metabolic pandemics.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. Electronic address: mherman1@bidmc.harvard.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Herman
authors.affiliation: Yale University School of Medicine, 950 Campbell Avenue, West Haven, CT 06516, USA; Veterans Affairs Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA. Electronic address: varman.samuel@yale.edu.
authors.forename: Varman T
authors.initials: VT
authors.lastname: Samuel
mesh_terms: D000818:Animals; D005632:Fructose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D050155:Lipogenesis / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D007328:Insulin; D005632:Fructose