De novo lipogenesis in health and disease

Metabolism. 2014 Jul;63(7):895-902. doi: 10.1016/j.metabol.2014.04.003. Epub 2014 Apr 12.

Abstract

Background: De novo lipogenesis (DNL) is a complex and highly regulated metabolic pathway. In normal conditions DNL converts excess carbohydrate into fatty acids that are then esterified to storage triacylglycerols (TGs). These TGs could later provide energy via β-oxidation. In human body this pathway is primarily active in liver and adipose tissue. However, it is considered to be a minor contributor to the serum lipid homeostasis. Deregulations in the lipogenic pathway are associated with diverse pathological conditions.

Scope of review: The present review focuses on our current understanding of the lipogenic pathway with special reference to the causes and consequences of aberrant DNL.

Major conclusions: The deregulation of DNL in the major lipogenic tissues of the human body is often observed in various metabolic anomalies - including obesity, non-alcoholic fatty liver disease and metabolic syndrome. In addition to that de novo lipogenesis is reported to be exacerbated in cancer tissues, virus infected cells etc. These observations suggest that inhibitors of the DNL pathway might serve as therapeutically significant compounds. The effectiveness of these inhibitors in treatment of cancer and obesity has been suggested by previous works.

General significance: De novo lipogenesis - which is an intricate and highly regulated pathway - can lead to adverse metabolic consequences when deregulated. Therapeutic targeting of this pathway may open a new window of opportunity for combating various lipogenesis-driven pathological conditions - including obesity, cancer and certain viral infections.

Keywords: Cancer; De novo lipogenesis; Fatty Acid Synthase; Non-alcoholic fatty liver disease; Obesity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Animals
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism
  • Energy Metabolism* / drug effects
  • Fatty Liver / drug therapy
  • Fatty Liver / etiology
  • Fatty Liver / metabolism*
  • Humans
  • Insulin Resistance
  • Lipid Regulating Agents / therapeutic use
  • Lipogenesis* / drug effects
  • Liver / drug effects
  • Liver / metabolism*
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / metabolism*
  • Molecular Targeted Therapy
  • Non-alcoholic Fatty Liver Disease
  • Obesity / drug therapy
  • Obesity / etiology
  • Obesity / metabolism*
  • Opportunistic Infections / metabolism
  • Opportunistic Infections / prevention & control
  • Opportunistic Infections / virology

Substances

  • Lipid Regulating Agents