Metabolic impact of weight loss induced reduction of adipose ACE-2 – Potential implication in COVID-19 infections?,Metabolism

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Metabolic impact of weight loss induced reduction of adipose ACE-2 – Potential implication in COVID-19 infections?
Metabolism ( IF 10.8 ) Pub Date : 2020-10-13 , DOI: 10.1016/j.metabol.2020.154401
Linna Li ₁ , Leonard Spranger ₂ , Dominik Soll ₂ , Finja Beer ₂ , Maria Brachs ₃ , Joachim Spranger ₄ , Knut Mai ₅

Affiliation

Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Clinical Research Unit, 10117 Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117 Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Clinical Research Unit, 10117 Berlin, Germany.

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/m²) 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.

中文翻译：

减肥引起的脂肪 ACE-2 减少对代谢的影响 – 对 COVID-19 感染的潜在影响？

背景和目标

血管紧张素转换酶 (ACE)-2 是脂肪组织代谢的调节剂。然而，脂肪 ACE-2 的人体数据很少。考虑到 ACE-2 被认为是负责 SARS-CoV-2 进入细胞的受体，因此需要更好地了解其调控。因此，我们表征了体重减轻过程中皮下脂肪 ACE-2 mRNA 表达的调节，以及 ACE-2 表达对体重减轻的影响，诱导了短期和长期葡萄糖代谢的改善。

方法

对 143 名受试者（年龄 > 18；BMI ≥ 27 kg/m ² ）在标准化 12 周饮食减肥计划前后进行了分析。随后，受试者被随机分为为期 12 个月的生活方式干预组或对照组（Maintain-Adults 试验）。胰岛素敏感性 (IS) 通过 HOMA-IR（作为肝脏 IS 的估计）和 ISI _Clamp （作为骨骼肌 IS 的估计）来估计。在减肥前后测量皮下脂肪组织中的 ACE-2 mRNA 表达（ACE-2 _AT ）。

结果

ACE-2 _AT不受肥胖影响，但在胰岛素抵抗受试者中降低。体重减轻导致 ACE-2 _AT下降（29.0 (20.0–47.9) vs. 21.0 (13.0–31.0)； p = 1.6 ∗ 10 ⁻⁷ ）。在 3 个月的减重过程中，ACE-2 _AT (ΔACE-2 _AT ) 的较小减少与 ISI _Clamp的较大改善相关 ( p = 0.013)，但与减重的时间延长无关。胰岛素抵抗的变化程度一直保留到第 12 个月，并且还可以通过 ΔACE-2 _AT的体重减轻诱导程度进行预测 ( p = 0.011)。