Abstract
Introduction: Neuropilin 1 (NRP-1) is a novel co-receptor promoting SARS-CoV-2 infectivity. Animal data indicate a role in trans-endothelial lipid transport and storage. As human data are sparse, we aimed to assess the role of NRP-1 in 2 metabolic active tissues in human obesity and in the context of weight loss-induced short- and long-term metabolic changes. Methods: After a standardized 12-week weight reduction program, 143 subjects (age >18; body mass index ≥27 kg/m<sup>2</sup>, 78% female) were randomized to a 12-month lifestyle intervention or a control group using a stratified randomization scheme. This was followed by 6-month follow-up without any intervention. Phenotyping was performed before and after weight loss, after 12-month intervention and after subsequent 6 months of follow-up. Tissue-specific insulin sensitivity was estimated by HOMA-IR (whole body and mostly driven by liver), insulin sensitivity index (ISI)<sub>Clamp</sub> (predominantly skeletal muscle), and free fatty acid (FFA) suppression during hyperinsulinemic-euglycemic clamp (FFA<sub>Supp</sub>) (predominantly adipose tissue). NRP-1 mRNA expression was measured in subcutaneous adipose tissue (NRP-1<sub>AT</sub>) and skeletal muscle (NRP-1<sub>SM</sub>) before and after weight loss. Results: NRP-1 was highly expressed in adipose tissue (7,893 [7,303–8,536] counts), but neither NRP-1<sub>AT</sub> nor NRP-1<sub>SM</sub> were related to estimates of obesity. Higher NRP-1<sub>AT</sub> was associated with stronger FFA<sub>Supp</sub> (r = −0.343, p = 0.003) and a tendency to higher ISI<sub>Clamp</sub> (r = 0.202, p = 0.085). Weight loss induced a decline of NRP-1<sub>AT</sub> but not NRP-1<sub>SM</sub>. This was more pronounced in subjects with stronger reduction of adipose ACE-2 mRNA expression (r = 0.250; p = 0.032) but was not associated with short- and long-term improvement of FFA<sub>Supp</sub> and ISI<sub>Clamp</sub>. Conclusion: NRP-1<sub>AT</sub> is related to adipose insulin sensitivity in obesity. Weight loss-induced decline of NRP-1<sub>AT</sub> seems not to be involved in metabolic short- and long-term improvements after weight loss. However, weight loss-induced reduction of both NRP-1<sub>AT</sub> and ACE-2<sub>AT</sub> indicates a lower susceptibility of adipose tissue for SARS-CoV-2 after body weight reduction.
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