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A lipase-independent pathway of lipid release and immune modulation by adipocytes

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Science  01 Mar 2019:
Vol. 363, Issue 6430, pp. 989-993
DOI: 10.1126/science.aaw2586

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Exosomes that fatten immune cells

Adipose tissue in mammals contains not only adipocytes (fat cells) but also a variety of immune cells—most notably, macrophages. Proper communication between these cell types is thought to be important for metabolic health. Flaherty et al. found that adipocytes release lipid-filled vesicles (AdExos) that serve as the primary source of lipid for adipose-resident macrophages (see the Perspective by Antonyak et al.). AdExos were present at low levels in the circulation of mice and were produced at twice the rate in obese versus lean animals. In vitro, AdExos induced differentiation of bone marrow precursor cells into cells resembling adipose-resident macrophages.

Science, this issue p. 989; see also p. 931

Abstract

To meet systemic metabolic needs, adipocytes release fatty acids and glycerol through the action of neutral lipases. Here, we describe a secondary pathway of lipid release from adipocytes that is independent of canonical lipolysis. We found that adipocytes release exosome-sized, lipid-filled vesicles (AdExos) that become a source of lipid for local macrophages. Adipose tissue from lean mice released ~1% of its lipid content per day via exosomes ex vivo, a rate that more than doubles in obese animals. AdExos and associated factors were sufficient to induce in vitro differentiation of bone marrow precursors into adipose tissue macrophage–like cells. Thus, AdExos are both an alternative pathway of local lipid release and a mechanism by which parenchymal cells can modulate tissue macrophage differentiation and function.

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