The role of lipins in innate immunity and inflammation

Balboa, Marı́a A.; Pablo, Nagore de; Meana, Clara; Balsinde, Jesús

doi:10.1016/j.bbalip.2019.06.003

Cited by 24 publications

(18 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rare mutations in the LPIN1 gene in humans are associated with a syndrome of acute, recurrent rhabdomyolysis that usually manifests in early childhood [ 59 , 65 , 66 , 67 , 68 ]. Rhabdomyolysis is an acute syndrome of skeletal muscle injury resulting in the release of intracellular metabolites and proteins, including creatine kinase and myoglobin, into the systemic circulation that can result in death from renal, cardiac, or hematologic dysfunction.…”

Section: Skeletal Musclementioning

confidence: 99%

Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity

Lutkewitte

Finck

2020

Biomolecules

View full text Add to dashboard Cite

Phosphatidic acid (PA) is a glycerophospholipid intermediate in the triglyceride synthesis pathway that has incredibly important structural functions as a component of cell membranes and dynamic effects on intracellular and intercellular signaling pathways. Although there are many pathways to synthesize and degrade PA, a family of PA phosphohydrolases (lipin family proteins) that generate diacylglycerol constitute the primary pathway for PA incorporation into triglycerides. Previously, it was believed that the pool of PA used to synthesize triglyceride was distinct, compartmentalized, and did not widely intersect with signaling pathways. However, we now know that modulating the activity of lipin 1 has profound effects on signaling in a variety of cell types. Indeed, in most tissues except adipose tissue, lipin-mediated PA phosphohydrolase activity is far from limiting for normal rates of triglyceride synthesis, but rather impacts critical signaling cascades that control cellular homeostasis. In this review, we will discuss how lipin-mediated control of PA concentrations regulates metabolism and signaling in mammalian organisms.

show abstract

Section: Skeletal Musclementioning

confidence: 99%

Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity

Lutkewitte

Finck

2020

Biomolecules

View full text Add to dashboard Cite

show abstract

“…We and others have shown that expression of a hypomorphic lipin-1 protein that lacks enzymatic activity attenuates proinflammatory macrophage responses by regulating glycerolipid synthesis (7)(8)(9). Lipin-1 enzymatic activity within macrophages contributes to disease pathogenesis of atherosclerosis, colitis, colon cancer, and LPS-induced inflammation [reviewed in (10)]. The overarching mechanism is likely due to lipin-1mediated diacylglycerol production leading to protein kinase C and AP-1 transcription factor activation driving proinflammatory macrophage activities (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Lipin-1 Contributes to IL-4 Mediated Macrophage Polarization

et al. 2020

View full text Add to dashboard Cite

Macrophage responses contribute to a diverse array of pathologies ranging from infectious disease to sterile inflammation. Polarization of macrophages determines their cellular function within biological processes. Lipin-1 is a phosphatidic acid phosphatase in which its enzymatic activity contributes to macrophage pro-inflammatory responses. Lipin-1 also possesses transcriptional co-regulator activity and whether this activity is required for macrophage polarization is unknown. Using mice that lack only lipin-1 enzymatic activity or both enzymatic and transcriptional coregulator activities from myeloid cells, we investigated the contribution of lipin-1 transcriptional co-regulator function toward macrophage wound healing polarization. Macrophages lacking both lipin-1 activities did not elicit IL-4 mediated gene expression to levels seen in either wildtype or lipin-1 enzymatically deficient macrophages. Furthermore, mice lacking myeloidassociated lipin-1 have impaired full thickness excisional wound healing compared to wild-type mice or mice only lacking lipin-1 enzymatic activity from myeloid cell. Our study provides evidence that lipin-1 transcriptional co-regulatory activity contributes to macrophage polarization and influences wound healing in vivo.

show abstract

“…We and others have shown that expression of a hypomorphic lipin-1 protein that lacks enzymatic activity attenuates pro-inflammatory macrophage responses by regulating glycerolipid synthesis [7; 8; 9]. Lipin-1 enzymatic activity within macrophages contributes to disease pathogenesis of atherosclerosis, colitis, colon cancer, and LPS induced inflammation (reviewed in [10]). The overarching mechanism is likely due to lipin-1-mediated diacylglycerol production leading to protein kinase C and AP-1 transcription factor activation driving pro-inflammatory macrophage activities [7; 8; 9].…”

Section: Introductionmentioning

confidence: 99%

Lipin-1 contributes to IL-4 mediated macrophage polarization

Chandran

Schilke

Blackburn

et al. 2019

Preprint

View full text Add to dashboard Cite

ABSTRACTMacrophage responses contribute to a diverse array of pathologies ranging from infectious disease to sterile inflammation. Polarization of macrophages determines their cellular function within biological processes. Lipin-1 is a phosphatidic acid phosphatase in which its enzymatic activity contributes to macrophage pro-inflammatory responses. Lipin-1 also possesses transcriptional co-regulator activity and whether this activity is required for macrophage polarization is unknown. Using mice that lack only lipin-1 enzymatic activity or both enzymatic and transcriptional coregulator activities from myeloid cells, we investigated the contribution of lipin-1 transcriptional co-regulator function towards macrophage wound healing polarization. Macrophages lacking both lipin-1 activities did elicit IL-4 mediated gene expression to levels seen in either wild-type or lipin-1 enzymatically deficient macrophages. Furthermore, we provide evidence that the lack of myeloid-associated lipin-1 transcriptional co-regulator activity leads to impaired full thickness excisional wound healing. Our study demonstrates that lipin-1 transcriptional co-regulatory activity contributes to macrophage polarization and the macrophage contribution to wound healing in vivo.

show abstract

The role of lipins in innate immunity and inflammation

Cited by 24 publications

References 108 publications

Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity

Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity

Lipin-1 Contributes to IL-4 Mediated Macrophage Polarization

Lipin-1 contributes to IL-4 mediated macrophage polarization

Contact Info

Product

Resources

About