Dominik Soll1, Finja Beer1, Leonard Spranger1, Linna Li1, Joachim Spranger1,2,3,4, Knut Mai5,6,7,8. 1. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, Berlin, Germany. 2. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, Berlin, Germany. 3. DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany. 4. NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal, Germany. 5. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, Berlin, Germany, knut.mai@charite.de. 6. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, Berlin, Germany, knut.mai@charite.de. 7. DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany, knut.mai@charite.de. 8. NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal, Germany, knut.mai@charite.de.
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/m2, 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)Clamp (predominantly skeletal muscle), and free fatty acid (FFA) suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). NRP-1 mRNA expression was measured in subcutaneous adipose tissue (NRP-1AT) and skeletal muscle (NRP-1SM) before and after weight loss. RESULTS: NRP-1 was highly expressed in adipose tissue (7,893 [7,303-8,536] counts), but neither NRP-1AT nor NRP-1SM were related to estimates of obesity. Higher NRP-1AT was associated with stronger FFASupp (r = -0.343, p = 0.003) and a tendency to higher ISIClamp (r = 0.202, p = 0.085). Weight loss induced a decline of NRP-1AT but not NRP-1SM. 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 FFASupp and ISIClamp. CONCLUSION: NRP-1AT is related to adipose insulin sensitivity in obesity. Weight loss-induced decline of NRP-1AT seems not to be involved in metabolic short- and long-term improvements after weight loss. However, weight loss-induced reduction of both NRP-1AT and ACE-2AT indicates a lower susceptibility of adipose tissue for SARS-CoV-2 after body weight reduction.
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/m2, 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)Clamp (predominantly skeletal muscle), and free fatty acid (FFA) suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). NRP-1 mRNA expression was measured in subcutaneous adipose tissue (NRP-1AT) and skeletal muscle (NRP-1SM) before and after weight loss. RESULTS: NRP-1 was highly expressed in adipose tissue (7,893 [7,303-8,536] counts), but neither NRP-1AT nor NRP-1SM were related to estimates of obesity. Higher NRP-1AT was associated with stronger FFASupp (r = -0.343, p = 0.003) and a tendency to higher ISIClamp (r = 0.202, p = 0.085). Weight loss induced a decline of NRP-1AT but not NRP-1SM. 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 FFASupp and ISIClamp. CONCLUSION: NRP-1AT is related to adipose insulin sensitivity in obesity. Weight loss-induced decline of NRP-1AT seems not to be involved in metabolic short- and long-term improvements after weight loss. However, weight loss-induced reduction of both NRP-1AT and ACE-2AT indicates a lower susceptibility of adipose tissue for SARS-CoV-2 after body weight reduction.
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