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 language | English |
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Pages (from-to) | 1499-1513.e8 |
Journal | Cell metabolism |
Volume | 34 |
Issue number | 10 |
DOIs | |
State | Published - 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