HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation

Abstract

Highlights d HILPDA is a lipid-induced, physiological inhibitor of ATGLmediated lipolysis d HILPDA-deficient macrophages show enhanced breakdown of triglycerides through ATGL d Reduced lipid storage in macrophages does not affect adipose tissue inflammation

Myeloid Cell Diversity and Impact of Metabolic Cues during Atherosclerosis

“…The relevance of our observations linking LIPA activity and efferocytosis to atherosclerosis needs to be further investigated, as multiple studies reported a correlation between LIPA variants and coronary artery disease [149,150]. into lipid droplets and foam cell formation [158]. In plaques, Hilpda mRNA was preferentially expressed in inflammatory macrophages ( Figure 2B).…”

Adipose tissue macrophages: Regulators of adipose tissue immunometabolism during obesity

“…Silencing LPL in ATMs from VAT of obese mice inhibited lipid accumulation in ATMs and increased serum FFA levels but did not effect serum triglyceride levels [ 53 ]. ATMs also express hypoxia inducible lipid droplet associated (Hilpda), a protein that mediates lipid accumulation in adipose tissue and whose expression is increased with obesity and FFA exposure [ 54 ]. Overexpression of acyl CoA: diacylglycerol acyltransferase 1 (DGAT1) protects mice from adipose tissue inflammation suggesting that inflammatory activation and lipid storage may be decoupled in some situations [ 55 ].…”

Impact and regulatory pathways of fatty acids in monocytes/macrophages and adipocytes

“…In cells, HILPDA is located in the endoplasmic reticulum and around lipid droplets. HILPDA was found to promote fat storage in liver cells (Mattijssen et al, 2014), cancer cells (Li et al, 2020), and macrophages ( van Dierendonck et al, 2020). This effect is mediated by suppression of TG triglyceride breakdown by inhibiting ATGL.…”

“…As the adipose tissue expands macrophages accumulate around adipocytes and adopt the morphology of foam cells (Shapiro et al, 2013). The foam cells have been suggested to contribute to the inflammatory phenotype of obese adipose tissue (Reilly and Saltiel, 2017), which in turn may promote the development of insulin resistance (Hotamisligil, 2006;Kotas and Medzhitov, 2015;Lumeng and Saltiel, 2011), although recent data have called this model into question (van Dierendonck et al, 2020).…”

“…van Dierendonck, X.A.M.H., de la Rosa Rodriguez, M.A., Georgiadi, A., Mattijssen, F., Dijk, W., van Weeghel, M., Singh, R., Borst, J.W., Stienstra, R., and Kersten, S. (2020). HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation.…”