Altered Cholesterol and Lipid Synthesis Mediates Hyperinflammation in COVID-19

Abstract

Recent data have revealed that fructose-rich diet triggers inflammation and lipid synthesis. Furthermore, lipid metabolism, cholesterol synthesis and sterol regulatory element binding protein-2 (SREBP-2) activation correlates with coronavirus disease 2019 (COVID-19)-induced cytokine storm. High fructose consumption result in SREBPs activation, altered cholesterol and lipid synthesis and may establish an innate immune memory in the cells, leading to severe COVID-19 in patients with obesity.

Keywords: COVID-19; cholesterol synthesis; cytokine storm; lipid synthesis; obesity.

Figure 1

Diet Induced Lipid Metabolism and Cholesterol Synthesis May Contribute to Hyperinflammatory Response Against COVID-19. Fructose-rich diet promotes de novo lipid synthesis through SREBP-2 and potentiates a nonspecific inflammatory response in response to an infection. A low dose of endotoxin in the blood due to deterioration of the intestinal barrier, high fat, cholesterol crystals (CCs), and activation of LXR induces development of immune memory in the cells. When an obese person encounters severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SREBP-2 is highly activated and the expression of fatty acid and cholesterol synthesis genes is upregulated. This leads to NLRP3 inflammasome and NF-kB activation and excessive cytokine production or cytokine storm. Abbreviations: COVID-19, coronavirus disease 2019; LPS, lipopolysaccharide; SREBP-2, sterol regulatory element binding protein-2.