ACE2 and energy metabolism: the connection between COVID-19 and chronic metabolic disorders

Abstract

The renin–angiotensin system (RAS) has currently attracted increasing attention due to its potential function in regulating energy homeostasis, other than the actions on cellular growth, blood pressure, fluid, and electrolyte balance. The existence of RAS is well established in metabolic organs, including pancreas, liver, skeletal muscle, and adipose tissue, where activation of angiotensin-converting enzyme (ACE) – angiotensin II pathway contributes to the impairment of insulin secretion, glucose transport, fat distribution, and adipokines production. However, the activation of angiotensin-converting enzyme 2 (ACE2) – angiotensin (1–7) pathway, a novel branch of the RAS, plays an opposite role in the ACE pathway, which could reverse these consequences by improving local microcirculation, inflammation, stress state, structure remolding, and insulin signaling pathway. In addition, new studies indicate the protective RAS arm possesses extraordinary ability to enhance brown adipose tissue (BAT) activity and induces browning of white adipose tissue, and consequently, it leads to increased energy expenditure in the form of heat instead of ATP synthesis. Interestingly, ACE2 is the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is threating public health worldwide. The main complications of SARS-CoV-2 infected death patients include many energy metabolism-related chronic diseases, such as diabetes. The specific mechanism leading to this phenomenon is largely unknown. Here, we summarize the latest pharmacological and genetic tools on regulating ACE/ACE2 balance and highlight the beneficial effects of the ACE2 pathway axis hyperactivity on glycolipid metabolism, as well as the thermogenic modulation.

Anti-SARS-CoV-2 Strategies and the Potential Role of miRNA in the Assessment of COVID-19 Morbidity, Recurrence, and Therapy

“…Several potential therapeutic strategies targeting ACE-2 have already been proposed to combat COVID-19. However, because of the critical metabolic and hemodynamic roles of ACE-2, including the regulation of glucose homeostasis [212] and the cleavage of angiotensin I and angiotensin II [210], these approaches may lead to severe clinical problems [213]. Therefore, transmembrane protease serine 2 (TMPRSS2), another main co-factor needed by the SARS-CoV-2 to enter human cells, might be an alternative target for COVID-19 [214].…”

Physical activity and COVID-19. The basis for an efficient intervention in times of COVID-19 pandemic

“…In this line, physical exercise has been postulated as the true “polypill” for all increased-risk- mortality causes [50] . Large observational studies also suggest that exercise itself can reduce the risk of all-cause and disease-specific mortality [ 51 , 52 ]. Indeed, a baseline sedentary lifestyle is an independent risk factor for mortality in hospitalized patients with COVID-19 [52] .…”

“…Large observational studies also suggest that exercise itself can reduce the risk of all-cause and disease-specific mortality [ 51 , 52 ]. Indeed, a baseline sedentary lifestyle is an independent risk factor for mortality in hospitalized patients with COVID-19 [52] . Yet, restrictions and public health recommendations such as stay-at-home orders, closures of parks, gymnasiums, and fitness centers to prevent the spread of the virus have had an impact, reducing daily physical activity (PA) [53] .…”

Pandemics of the 21st Century: The Risk Factor for Obese People

“…Consequently, the increased energy is released in the form of heat instead of ATP synthesis. The affected metabolism of energy during viral infection in individuals with obesity leads to a worsening of their pathological conditions [130].…”