Extended Data Fig. 7. Schematic illustration of mechanisms underlying SARS-CoV-2-induced adipose atrophy and weight loss.

SARS-CoV-2 infection triggers dyspnea and pathological changes in the infected lung tissues, including pulmonary edema, inflammation, and obstruction of pulmonary alveoli. These pathological alterations induce local hypoxia in the lung tissue and systemic hypoxia in other tissues. Hypoxia serves as a potent factor to induce VEGF expression through the HIF1α-VEGF promoter dependent mechanism. Non-heparin-binding smaller isoforms of VEGF enters the circulation and produces systemic effects on multiple tissues and organs. In the adipose tissue, the local and circulating VEGF promotes browning phenotypes of WATs and BAT. Activation of BAT and browning of WATs augment non-shivering thermogenesis (NST) by heat production, which may partly explain the SARS-CoV-2-induced fever. NST activation by SARS-CoV-2 also markedly augments energy consumption, leading to a lean phenotype and clinically manifesting as adipose atrophy and weight loss.