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

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.