The Sweet Path to Metabolic Demise: Fructose and Lipid Synthesis

Trends Endocrinol Metab. 2016 Oct;27(10):719-730. doi: 10.1016/j.tem.2016.06.005. Epub 2016 Jul 4.

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.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Fructose / metabolism*
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology
  • Lipid Metabolism / genetics
  • Lipid Metabolism / physiology
  • Lipogenesis / genetics
  • Lipogenesis / physiology
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • Insulin
  • Fructose