Dietary lipids inhibit mitochondria transfer to macrophages to divert adipocyte-derived mitochondria into the blood

Nicholas Borcherding, Wentong Jia, Rocky Giwa, Rachael L. Field, John R. Moley, Benjamin J. Kopecky, Mandy M. Chan, Bin Q. Yang, Jessica M. Sabio, Emma C. Walker, Omar Osorio, Andrea L. Bredemeyer, Terri Pietka, Jennifer Alexander-Brett, Sharon Celeste Morley, Maxim N. Artyomov, Nada A. Abumrad, Joel Schilling, Kory Lavine, Clair CreweJonathan R. Brestoff

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Adipocytes transfer mitochondria to macrophages in white and brown adipose tissues to maintain metabolic homeostasis. In obesity, adipocyte-to-macrophage mitochondria transfer is impaired, and instead, adipocytes release mitochondria into the blood to induce a protective antioxidant response in the heart. We found that adipocyte-to-macrophage mitochondria transfer in white adipose tissue is inhibited in murine obesity elicited by a lard-based high-fat diet, but not a hydrogenated-coconut-oil-based high-fat diet, aging, or a corn-starch diet. The long-chain fatty acids enriched in lard suppress mitochondria capture by macrophages, diverting adipocyte-derived mitochondria into the blood for delivery to other organs, such as the heart. The depletion of macrophages rapidly increased the number of adipocyte-derived mitochondria in the blood. These findings suggest that dietary lipids regulate mitochondria uptake by macrophages locally in white adipose tissue to determine whether adipocyte-derived mitochondria are released into systemic circulation to support the metabolic adaptation of distant organs in response to nutrient stress.

Original languageEnglish
Pages (from-to)1499-1513.e8
JournalCell metabolism
Volume34
Issue number10
DOIs
StatePublished - Oct 4 2022

Keywords

  • CD36
  • EXT1
  • aging
  • beige fat
  • brown adipose tissue
  • cell-free mitochondria
  • fatty acids
  • heparan sulfate
  • horizontal mitochondria transfer
  • intercellular mitochondria transfer
  • lipids
  • macrophage
  • mitochondria
  • obesity
  • palmitate
  • white adipose tissue

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