HILPDA uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation
ABSTRACT Obesity promotes accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency in bone marrow-derived macrophages markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids in lipid droplets. Decreased lipid storage in HILPDA-deficient macrophages could be almost completely rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory or metabolic parameters, despite markedly reducing lipid storage in adipose tissue macrophages. Our data indicate that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Overall, our data question the importance of lipid storage in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation..
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Preprint| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
bioRxiv.org - (2021) vom: 15. Dez. Zur Gesamtaufnahme - year:2021 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
van Dierendonck, Xanthe A.M.H. [VerfasserIn] |
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| Links: |
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| doi: |
10.1101/566802 |
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| PPN (Katalog-ID): |
XBI000465208 |
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| 520 | |a ABSTRACT Obesity promotes accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency in bone marrow-derived macrophages markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids in lipid droplets. Decreased lipid storage in HILPDA-deficient macrophages could be almost completely rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory or metabolic parameters, despite markedly reducing lipid storage in adipose tissue macrophages. Our data indicate that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Overall, our data question the importance of lipid storage in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation. | ||
| 700 | 1 | |a de la Rosa Rodriguez, Montserrat A. |e verfasserin |4 aut | |
| 700 | 1 | |a Georgiadi, Anastasia |e verfasserin |4 aut | |
| 700 | 1 | |a Mattijssen, Frits |e verfasserin |4 aut | |
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| 700 | 1 | |a Kersten, Sander |e verfasserin |4 aut | |
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