Angiotensin converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. ACE2 is one of the key enzymes in renin-angiotensin system and plays a vital role in the maintenance of cardiovascular function. ACE/ACE2 balance is critical in the regulation of blood pressure, electrolyte homeostasis, vascular and cardiac remodeling and inflammation. ACE2 was shown to be abundantly present in human epithelial cells of the lung and enterocytes of the small intestine as well as in endothelial cells of the arterial and venous vessels. ACE2 and TMPRSS2 are colocalized on the cell surface and produced a critical step host cell entry of SARS-CoV-2. TMPRSS2-cleaved ACE2 permits SARS-CoV-2 host cell entry however, ADAM17-cleaved ACE2 produces protective effects in several organs. Differently, basigin (CD147) was suggested as a putative alternate receptor for SARS-CoV-2 entry into endothelial cells. The intestinal ACE2 receptor is associated with the neutral amino acid transporter B0AT1 and ACE2 is necessary for the expression of this transporter on the luminal surface of intestinal epithelial cells. There is a good association between the localization of SARS-CoV-2 binding receptor ACE2 and the disease target organs in respiratory, cardiovascular and gastrointestinal systems. Decreased expression of ACE2, being a receptor for coronavirus, would prevent cellular entry of the virus thereby reducing progression of the infection. However, increased ACE2 expression produces beneficial health effects. Further studies are needed to clarify this conflicting situation. Currently, it is recommended to continue the therapy with ACE2-increasing drugs in patients with COVID-19.

The effects of high-fructose diet on adipose tissue insulin signaling and inflammatory process have been poorly documented. In this study, we examined the influences of long-term fructose intake and resveratrol supplementation on the expression of genes involved in insulin signaling and the levels of inflammatory cytokines and sex hormones in the white adipose tissues of male and female rats. Consumption of high-fructose diet for 24 weeks increased the expression of genes involved in insulin signaling includingIR,IRS-1,IRS-2,Akt,PI3K,eNOS,mTOR, andPPARγ, despite induction of proinflammatory markers, iNOS, TNFα, IL-1β, IL-18, MDA, and ALT, as well as anti-inflammatory factors, IL-10 and Nrf2 in adipose tissues from males and females. Total and free testosterone concentrations of adipose tissues were impaired in males but increased in females, although there were no changes in their blood levels. Resveratrol supplementation markedly restored the levels of MDA, IL6, IL-10, and IL-18, as well asiNOS,Nrf2, andPI3KmRNA, in adipose tissues of both genders. Dietary fructose activates both insulin signaling and inflammatory pathway in the adipose tissues of male and female rats proposing no correlation between the tissue insulin signaling and inflammation. Resveratrol has partly modulatory effects on fructose-induced changes.

The excessive intake of fructose in the regular human diet could be related to global increases in metabolic disorders. Sugar-sweetened soft drinks, mostly consumed by children, adolescents, and young adults, are the main source of added fructose. Dietary high-fructose can increase intestinal permeability and circulatory endotoxin by changing the gut barrier function and microbial composition. Excess fructose transports to the liver and then triggers inflammation as well as de novo lipogenesis leading to hepatic steatosis. Fructose also induces fat deposition in adipose tissue by stimulating the expression of lipogenic genes, thus causing abdominal adiposity. Activation of the inflammatory pathway by fructose in target tissues is thought to contribute to the suppression of the insulin signaling pathway producing systemic insulin resistance. Moreover, there is some evidence that high intake of fructose negatively affects both male and female reproductive systems and may lead to infertility. This review addresses dietary high-fructose-induced deteriorations that are obvious, especially in gut permeability, microbiota, abdominal fat accumulation, insulin signaling, and reproductive function. The recognition of the detrimental effects of fructose and the development of relevant new public health policies are necessary in order to prevent diet-related metabolic disorders.