Sunday, January 2, 2022

Lipid dysregulation

Compared to control subjects, patients with IBS show significantly higher lipid levels in their blood. Elevated levels of certain lipids, such as arachidonic acid, in plasma may even serve as putative biological markers in this condition. Lipids have been shown to sensitize mechanoreceptor response and increase perception of gut distention. Some of probiotics beneficial to irritable bowel - such as Lactobacillus or Bifidobacterium - are related to the lipid metabolism displaying lipid-lowering effects.

Dysregulation of lipid metabolism has been a hallmark of many other diseases and conditions including cancer and COVID-19.

Lipids play a crucial role throughout the viral life cycle, and viruses are known to exploit lipid pathways to affect host metabolism. Numerous observational studies have shown potential beneficial effects of lipid-lowering treatment on the course of COVID-19 with significant improved prognosis and reduced mortality. On the other hand, bioactive lipids have been proposed as potential drugs helping to combat COVID-19.  

Here is what we know.

Glycerolipids and glycerophospholipids are markers of severe COVID-19, increased in ARDS (acute respiratory distress syndrome). Lipid storm can be self-destructive enhancing peptide-mediated cytokine storms. Dysregulation of lipid metabolism may be a defining feature of the severity of COVID-19. 

Shorter chain lipids were found at increased levels after successful COVID vaccination.

Sphingolipids, especially Sphingomyelin (SM) that associates with cholesterol to form lipid rafts that promote Coronavirus entry on the cellular surface (help viral S-protein to bind the cellular receptor ACE2) are decreased in asymptomatic patients. Other ether lipids [including PC O-35:4 (i), LPC O-18:1 (i) and LPE O-18:2], sphingomyelin (SM34:1; O2), and fatty acids (including FA 18:1 and FA 20:0) are also decreased in asymptomatic COVID.

Lysophospholipids including lysophosphatidylserine (LPS) 18:1, lysophosphatidic acid (LPA) 18:1 and LPA 18:0, lysophosphatidylcholine (LPC) 22:1, and lysophosphatidylinositol (LPI) 18:1 are generally decreased in asymptomatic COVID-19 patients. - Diacylglycerol (DG) 30:0 (14:0_16:0), DG 36:5 (18:2_18:3), phosphatidylcholine (PC) 36:5 (18:2_18:3), and phosphatidylethanolamine (PE) 36:2 (18:0_18:2) are increased. These lipids seem to have a protective effect in COVID-19.

Bioactive lipids - phospholipids including Plasmalogens and PAFs, gamma-linolenic acid (GLA), dihomo-GLA (DGLA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) help cells of the innate immune system - macrophages - with phagocytosis. Targeting membrane sphingolipids and interfering with the virus lipid metabolism could represent a promising path to follow towards the development of COVID-19 treatments. 


Lee SH, Kim KN, Kim KM, Joo NS. Irritable bowel syndrome may be associated with elevated alanine aminotransferase and metabolic syndrome. Yonsei medical journal. 2016 Jan 1;57(1):146-52.

Serra J, Salvioli B, Azpiroz F, Malagelada JR. Lipid-induced intestinal gas retention in irritable bowel syndrome. Gastroenterology. 2002 Sep 1;123(3):700-6.

Schwarz B, Sharma L, Roberts L, Peng X, Bermejo S, Leighton I, Casanovas-Massana A, Minasyan M, Farhadian S, Ko AI, Cruz CS. Cutting edge: Severe SARS-CoV-2 infection in humans is defined by a shift in the serum lipidome, resulting in dysregulation of eicosanoid immune mediators. The Journal of Immunology. 2021 Jan 15;206(2):329-34.

Hao Y, Zhang Z, Feng G, Chen M, Wan Q, Lin J, Wu L, Nie W, Chen S. Distinct lipid metabolic dysregulation in asymptomatic COVID-19. Iscience. 2021 Sep 24;24(9):102974.

Surma S, Banach M, Lewek J. COVID-19 and lipids. The role of lipid disorders and statin use in the prognosis of patients with SARS-CoV-2 infection. Lipids in Health and Disease. 2021 Dec;20(1):1-4.

Casari I, Manfredi M, Metharom P, Falasca M. Dissecting lipid metabolism alterations in SARS-CoV-2. Progress in Lipid Research. 2021 Feb 8:101092.

Demopoulos CA. Is Platelet-Activating Factor (PAF) a missing link for elucidating the mechanism of action of the coronavirus SARS-CoV-2 and explaining the side effects-complications of Covid-19 disease?.

Deng Y, Angelova A. Coronavirus-Induced Host Cubic Membranes and Lipid-Related Antiviral Therapies: A Focus on Bioactive Plasmalogens. Frontiers in Cell and Developmental Biology. 2021 Mar 12;9:551.

Martín-Fernández M, Aller R, Heredia-Rodríguez M, Gómez-Sánchez E, Martínez-Paz P, Gonzalo-Benito H, Sánchez-de Prada L, Gorgojo Ó, Carnicero-Frutos I, Tamayo E, Tamayo-Velasco Á. Lipid peroxidation as a hallmark of severity in COVID-19 patients. Redox biology. 2021 Dec 1;48:102181.

Das UN. Bioactive lipids-based therapeutic approach to COVID-19 and other similar infections. Archives of Medical Science. 2021.

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