Abstract
Background & aims: Angiotensin converting enzyme (ACE)-2 is a modulator of adipose tissue metabolism. However, human data of adipose ACE-2 is rarely available. Considering that, ACE-2 is believed to be the receptor responsible for cell entry of SARS-CoV-2, a better understanding of its regulation is desirable. We therefore characterized the modulation of subcutaneous adipose ACE-2 mRNA expression during weight loss and the impact of ACE-2 expression on weight loss induced short- and long-term improvements of glucose metabolism.
Methods: 143 subjects (age > 18; BMI ≥ 27 kg/m 2 ) were analyzed before and after a standardized 12-week dietary weight reduction program. Afterwards subjects were randomized to a 12-month lifestyle intervention or a control group (Maintain-Adults trial). Insulin sensitivity (IS) was estimated by HOMA-IR (as an estimate of liver IS) and ISI Clamp (as an estimate of skeletal muscle IS). ACE-2 mRNA expression (ACE-2 AT ) was measured in subcutaneous adipose tissue before and after weight loss.
Results: ACE-2 AT was not affected by obesity, but was reduced in insulin resistant subjects. Weight loss resulted in a decline of ACE-2 AT (29.0 (20.0-47.9) vs. 21.0 (13.0-31.0); p = 1.6 ∗ 10 -7 ). A smaller reduction of ACE-2 AT (ΔACE-2 AT ) was associated with a larger improvement of ISI Clamp (p = 0.013) during weight reduction over 3 months, but not with the extend of weight loss. The degree of changes in insulin resistance were preserved until month 12 and was also predicted by the weight loss induced degree of ΔACE-2 AT (p = 0.011).
Conclusions: Our data indicate that subcutaneous adipose ACE-2 expression correlates with insulin sensitivity. Weight loss induced decline of subcutaneous adipose ACE-2 expression might affect short- and long-term improvement of myocellular insulin sensitivity, which might be also relevant in the context of ACE-2 downregulation by SARS-CoV-2.
Trial registration: ClinicalTrials.gov number: NCT00850629 , https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.
Keywords: ACE-2; Adipose tissue; Insulin sensitivity; Obesity; Weight loss.
【저자키워드】 obesity, ACE-2, Adipose tissue, Insulin sensitivity, weight loss, 【초록키워드】 SARS-CoV-2, Trial, Intervention, metabolism, improvement, Randomized, sensitivity, weight, insulin resistance, age, receptor, BMI, insulin, expression, liver, Glucose, angiotensin, Skeletal muscle, reduction, weight loss, Regulation, control group, modulation, tissue, subject, enzyme, cell entry, downregulation, mRNA expression, adipose, ISI, Affect, Clamp, was measured, responsible, predicted, analyzed, characterized, changes in, subjects, not affected, was reduced, preserved, tissue metabolism, 【제목키워드】 COVID-19, reduction, weight loss, metabolic, adipose, Potential,