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严重肥胖和胰岛素抵抗成人中的游离脂肪酸动态变化:与rs9939609风险等位基因无关联。

NEFA Dynamics in Adults With Severe Obesity and Insulin Resistance: No Coupling to the rs9939609 Risk Allele.

作者信息

Mostad Ingrid Løvold, Grill Valdemar

机构信息

Department of Clinical Nutrition and Speech-Language Therapy, Clinic of Rehabilitation, St. Olavs hospital-Trondheim University Hospital, NO 7006 Trondheim, Norway.

Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NO 7491 Trondheim, Norway.

出版信息

J Endocr Soc. 2023 Aug 2;7(9):bvad101. doi: 10.1210/jendso/bvad101.

DOI:10.1210/jendso/bvad101
PMID:37873504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10590638/
Abstract

CONTEXT

The gene is highly expressed in adipose tissues; however, whether nonesterified fatty acids (NEFA) dynamics are impacted by has not been rigorously tested for in a uniformly obese study population comprising both sexes.

OBJECTIVE

To test for associations of the rs9939609 risk allele with NEFA suppression.

METHODS

We investigated 97 subjects with severe obesity but without diabetes, having genotype TT (n = 32), AT (n = 31), or AA (n = 34) in a cross-sectional observation study. NEFA suppression was assessed from a low-dose hyperinsulinemic euglycemic clamp with glucose-tracer as well as from the response to a standardized meal. Insulin sensitivity was assessed by hepatic and total insulin sensitivity measurements in the clamp and by the Matsuda index during the meal. Variables of possible importance for NEFA dynamics were primarily assessed by linear regression.

RESULTS

No genotype associations with fasting or suppressed NEFA were found, whether in the clamp or meal situation ( > .7 for all comparisons). Independent of genotype, higher fasting concentrations of NEFA and larger NEFA suppression were found in female compared with male subjects. Fasting NEFA or degree of suppression were not associated with total fat mass or body mass index. The respiratory quotient was negatively associated with NEFA suppression.

CONCLUSION

In a gender-mixed adult population of obese individuals, an obesity-risk allele did not affect fasting NEFA nor suppression thereof. These negative results on NEFA dynamics appear strengthened by the documentation of gender influence and associations with parameters reflective of insulin resistance.

摘要

背景

该基因在脂肪组织中高度表达;然而,在一个包含男女两性的统一肥胖研究人群中,非酯化脂肪酸(NEFA)动态是否受到影响尚未经过严格测试。

目的

测试rs9939609风险等位基因与NEFA抑制之间的关联。

方法

在一项横断面观察研究中,我们调查了97名患有严重肥胖但无糖尿病的受试者,其基因型为TT(n = 32)、AT(n = 31)或AA(n = 34)。通过使用葡萄糖示踪剂的低剂量高胰岛素正常血糖钳夹以及对标准化餐食的反应来评估NEFA抑制。通过钳夹过程中的肝脏和总胰岛素敏感性测量以及餐食期间的松田指数来评估胰岛素敏感性。对NEFA动态可能具有重要意义的变量主要通过线性回归进行评估。

结果

无论是在钳夹还是餐食情况下,均未发现基因型与空腹或抑制的NEFA之间存在关联(所有比较的P>0.7)。与基因型无关,女性受试者的空腹NEFA浓度较高,NEFA抑制程度也较大。空腹NEFA或抑制程度与总脂肪量或体重指数无关。呼吸商与NEFA抑制呈负相关。

结论

在一个由肥胖个体组成的成年男女混合人群中,一种肥胖风险等位基因既不影响空腹NEFA,也不影响其抑制作用。关于NEFA动态的这些阴性结果似乎因性别影响以及与反映胰岛素抵抗的参数之间的关联的记录而得到加强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/10590638/9a465ee3a8ce/bvad101f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/10590638/abb9276d283c/bvad101f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/10590638/aa07e2290c8a/bvad101f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/10590638/9a465ee3a8ce/bvad101f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/10590638/abb9276d283c/bvad101f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/10590638/aa07e2290c8a/bvad101f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/10590638/9a465ee3a8ce/bvad101f3.jpg

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本文引用的文献

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J Clin Invest. 2021 Nov 1;131(21). doi: 10.1172/JCI151818.
2
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PLoS One. 2021 Mar 8;16(3):e0248247. doi: 10.1371/journal.pone.0248247. eCollection 2021.
3
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Nutrients. 2020 Dec 17;12(12):3857. doi: 10.3390/nu12123857.
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Impact of a FTO gene risk variant on variables of energy metabolism in adults with obesity class 2 and 3.FTO基因风险变异对2级和3级肥胖成年人能量代谢变量的影响。
Metabol Open. 2019 Feb 19;1:3-6. doi: 10.1016/j.metop.2019.02.001. eCollection 2019 Mar.
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Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.肥胖症中全基因组身体活动相互作用——对200452名成年人的荟萃分析
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