SARS-CoV-2-infected adipocytes drive adipose inflammation and hepatocyte lipid accumulation

Obesity and fatty liver may worsen COVID-19 outcomes, but the mechanism by which adipose tissue infection contributes to liver injury is unclear. We aimed to determine whether SARS-CoV-2 infection of human adipocytes promotes inflammation and hepatic lipid accumulation, and to identify the underlying mechanisms.

Mesenchymal stem cell-derived human adipocytes were infected with Wuhan SARS-CoV-2 strain. Cell-surface ACE2 expression was measured in adipocytes. Viral replication and infectious titers were measured, and adipocyte morphology, cytokine/adipokine secretion, and lipid metabolism gene expression were analyzed. Culture supernatants from infected adipocytes were then applied to Huh7.5 hepatocytes to evaluate steatosis and fibrogenic activation.

SARS-CoV-2 productively infected adipocytes, which express cell-surface ACE2, leading to hypertrophy, increased IL-6 secretion, a higher leptin/adiponectin ratio, and lipid droplet accumulation. The infectious virus was released into the supernatants. However, neutralization with anti-Spike antibodies or UV-C inactivation abolished this effect, indicating that hepatocyte lipid accumulation depended on infectious virus rather than on soluble adipocyte-derived mediators alone.

Adipose tissue can serve as a source of infectious SARS-CoV-2 that promotes hepatic steatosis and fibrogenic activation, suggesting a mechanism by which obesity and fatty liver may worsen COVID-19 outcomes, although the contribution of residual infectious virus versus adipocyte-derived factors cannot be fully distinguished. At present, the data do not support an independent role for adipocyte-derived soluble mediators in this effect. The study is intended as a mechanistic in vitro analysis of adipocyte-hepatocyte crosstalk during SARS-CoV-2 infection.