Obesity alters Ace2 and Tmprss2 expression in lung, trachea, and esophagus in a sex-dependent manner: Implications for COVID-19

Abstract

Obesity is a major risk factor for SARS-CoV-2 infection and COVID-19 severity. The underlying basis of this association is likely complex in nature. The host-cell receptor angiotensin converting enzyme 2 (ACE2) and the type II transmembrane serine protease (TMPRSS2) are important for viral cell entry. It is unclear whether obesity alters expression of Ace2 and Tmprss2 in the lower respiratory tract. Here, we show that: 1) Ace2 expression is elevated in the lung and trachea of diet-induced obese male mice and reduced in the esophagus of obese female mice relative to lean controls; 2) Tmprss2 expression is increased in the trachea of obese male mice but reduced in the lung and elevated in the trachea of obese female mice relative to lean controls; 3) in chow-fed lean mice, females have higher expression of Ace2 in the lung and esophagus as well as higher Tmprss2 expression in the lung but lower expression in the trachea compared to males; and 4) in diet-induced obese mice, males have higher expression of Ace2 in the trachea and higher expression of Tmprss2 in the lung compared to females, whereas females have higher expression of Tmprss2 in the trachea relative to males. Our data indicate diet- and sex-dependent modulation of Ace2 and Tmprss2 expression in the lower respiratory tract and esophagus. Given the high prevalence of obesity worldwide and a sex-biased mortality rate, we discuss the implications and relevance of our results for COVID-19.

The Impact of Angiotensin-Converting Enzyme 2 (ACE2) Expression Levels in Patients with Comorbidities on COVID-19 Severity: A Comprehensive Review

“…In fact, an increased ACE2 expression in COPD patients who are overweight compared to those who are not overweight was observed and studies in mice showed that obese male mice fed a High Fat Diet displayed a significantly elevated expression of ACE2 in the lung and trachea relative to chow-fed lean male mice [ 7 , 81 ].…”

“…Human-to-human transmission is well established for this virus, which spreads through direct contact or aerosolized nasal droplets [ 3 , 4 , 5 , 6 ]. The viral entry through the respiratory tract is thought to be the major route of infection [ 7 ].…”

DNA damage contributes to age-associated differences in SARS-CoV-2 infection

“…Due to DNA damage was accumulated during aging, our findings provide an explanation of age associated severity and outcome of COVID-19, although other characteristics and alterations of aging could not be excluded. Apart from aging, other factors involved in COVID-19 progression, such as smoking and obesity, were associated with ACE2 expression [34][35][36] . Moreover, both smoking and obesity could cause, or at least associate with the level of DNA damage 37,38 , which suggest a potential role of DNA damage in smoking and obesity related risk of COVID-19.…”

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