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Am J Physiol Endocrinol Metab. 2014 Aug 15;307(4):E374-83. doi: 10.1152/ajpendo.00187.2014. Epub 2014 Jul 1.

Lipid storage by adipose tissue macrophages regulates systemic glucose tolerance.

Author information

1
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
2
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts Michael.Czech@umassmed.edu Myriam.Aouadi@umassmed.edu Michael.Czech@umassmed.edu.

Abstract

Proinflammatory pathways in adipose tissue macrophages (ATMs) can impair glucose tolerance in obesity, but ATMs may also be beneficial as repositories for excess lipid that adipocytes are unable to store. To test this hypothesis, we selectively targeted visceral ATMs in obese mice with siRNA against lipoprotein lipase (LPL), leaving macrophages within other organs unaffected. Selective silencing of ATM LPL decreased foam cell formation in visceral adipose tissue of obese mice, consistent with a reduced supply of fatty acids from VLDL hydrolysis. Unexpectedly, silencing LPL also decreased the expression of genes involved in fatty acid uptake (CD36) and esterification in ATMs. This deficit in fatty acid uptake capacity was associated with increased circulating serum free fatty acids. Importantly, ATM LPL silencing also caused a marked increase in circulating fatty acid-binding protein-4, an adipocyte-derived lipid chaperone previously reported to induce liver insulin resistance and glucose intolerance. Consistent with this concept, obese mice with LPL-depleted ATMs exhibited higher hepatic glucose production from pyruvate and glucose intolerance. Silencing CD36 in ATMs also promoted glucose intolerance. Taken together, the data indicate that LPL secreted by ATMs enhances their ability to sequester excess lipid in obese mice, promoting systemic glucose tolerance.

KEYWORDS:

adipose tissue macrophages; foam cells; insulin resistance; obesity; siRNA

PMID:
24986598
PMCID:
PMC4137117
DOI:
10.1152/ajpendo.00187.2014
[Indexed for MEDLINE]
Free PMC Article

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