Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity

Mol Cell. 2021 Sep 16;81(18):3708-3730. doi: 10.1016/j.molcel.2021.08.027.

Abstract

Lipids play crucial roles in signal transduction, contribute to the structural integrity of cellular membranes, and regulate energy metabolism. Questions remain as to which lipid species maintain metabolic homeostasis and which disrupt essential cellular functions, leading to metabolic disorders. Here, we discuss recent advances in understanding lipid metabolism with a focus on catabolism, synthesis, and signaling. Technical advances, including functional genomics, metabolomics, lipidomics, lipid-protein interaction maps, and advances in mass spectrometry, have uncovered new ways to prioritize molecular mechanisms mediating lipid function. By reviewing what is known about the distinct effects of specific lipid species in physiological pathways, we provide a framework for understanding newly identified targets regulating lipid homeostasis with implications for ameliorating metabolic diseases.

Keywords: cancer; cellular metabolism; free fatty acids (FFAs); lipid metabolism; lipidomics; lipids; lipotoxicity; obesity; triacylglycerol accumulation.

Publication types

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

MeSH terms

  • Animals
  • Chromatin / metabolism
  • Disease
  • Energy Metabolism / physiology
  • Health
  • Homeostasis / physiology
  • Humans
  • Immunity / physiology
  • Lipid Metabolism / physiology*
  • Lipidomics / methods
  • Lipids / physiology
  • Metabolic Diseases / metabolism*
  • Metabolic Diseases / physiopathology
  • Metabolomics / methods
  • Microbiota / physiology
  • Signal Transduction / physiology*

Substances

  • Chromatin
  • Lipids