Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport

Nat Commun. 2017 Apr 19;8:15010. doi: 10.1038/ncomms15010.

Abstract

Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in response to pharmacological stimulation of thermogenesis linked to increased HDL levels in APOE*3-Leiden.CETP mice. Both cold-induced and pharmacological thermogenic activation enhances HDL remodelling, which is associated with specific lipidomic changes in mouse and human HDL. Furthermore, thermogenic stimulation promotes HDL-cholesterol clearance and increases macrophage-to-faeces reverse cholesterol transport in mice. Mechanistically, we show that intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL by scavenger receptor B-I are the driving forces of HDL-cholesterol disposal in liver. Our findings corroborate the notion that high metabolic activity of thermogenic adipocytes confers atheroprotective properties via increased systemic cholesterol flux through the HDL compartment.

Publication types

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

MeSH terms

  • Adipocytes / metabolism*
  • Animals
  • Biological Transport
  • CD36 Antigens / metabolism
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use
  • Cholesterol / metabolism*
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / metabolism
  • Cold Temperature
  • Humans
  • Hyperlipidemias / drug therapy
  • Hyperlipidemias / pathology
  • Lipolysis
  • Lipoprotein Lipase / metabolism
  • Lipoproteins, HDL / metabolism*
  • Liver / metabolism
  • Male
  • Metabolome
  • Mice, Inbred C57BL
  • Thermogenesis*
  • Triglycerides / metabolism

Substances

  • CD36 Antigens
  • Cardiotonic Agents
  • Cholesterol, HDL
  • Lipoproteins, HDL
  • Triglycerides
  • Cholesterol
  • Lipoprotein Lipase