Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated free fatty acids: A mechanistic case-control and a population-based cohort study.
Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated free fatty acids: A mechanistic case-control and a population-based cohort study.
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肥胖者的高胰岛素血症和胰岛素抵抗可能是对游离脂肪酸升高的稳态反应的一部分：一项机制病例对照和基于人群的队列研究
DOI：
10.1016/j.ebiom.2021.103264
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发表时间：
2021-03
期刊：
影响因子：
11.1
通讯作者：
Jansson PA
中科院分区：
文献类型：
--
作者：
Fryk E;Olausson J;Mossberg K;Strindberg L;Schmelz M;Brogren H;Gan LM;Piazza S;Provenzani A;Becattini B;Lind L;Solinas G;Jansson PA
人们普遍认为，在肥胖症中，游离脂肪酸（FFA）会导致胰岛素抵抗和高血糖，从而导致高胰岛素血症。然而，在血糖正常的受试者中观察到高胰岛素血症，因此应重新评价上述范例。我们描述了两项研究：MD-脂解，一项通过全身代谢分析、微透析测量脂肪组织脂解和脂肪组织基因组学研究肥胖驱动的胰岛素抵抗机制的病例对照研究;以及POEM，一项用于验证MD-脂解研究中观察到的与肥胖和胰岛素抵抗相关的循环代谢物差异的队列研究。在MD-脂解研究中，高胰岛素血症与FFA升高相关。脂肪分解，每脂肪组织质量或脂肪细胞表面的甘油释放评估，肥胖和瘦个体之间是相似的。肥胖受试者的脂肪组织表现出介导儿茶酚胺驱动的脂解、脂质储存的基因表达减少，而驱动增生生长的基因表达增加。在POEM研究中，FFA水平在空腹血糖正常、空腹胰岛素和C肽水平高的肥胖超重受试者中特别升高。在血糖正常的肥胖受试者中，空腹时FFA循环水平升高是导致空腹高胰岛素血症的主要代谢紊乱候选因素。高FFA的肥胖与正常血脂更好地解释了脂肪量增加，而不是脂肪组织胰岛素抵抗。这些结果支持高胰岛素血症和胰岛素抵抗可能是对肥胖和FFA增加的稳态适应性反应的一部分。瑞典研究理事会（2016-02660）;糖尿病基金会（DIA 2017 -250; DIA 2018 -384; DIA 2020 -564）;诺和诺德基金会（NNF 17 OC 0027458; NNF 19 OC 0057174）;癌症基金会（CAN 2017/472; 200840 PjF）;瑞典ALF协议（2018-74560）。
It is commonly accepted that in obesity free fatty acids (FFA) cause insulin resistance and hyperglycemia, which drives hyperinsulinemia. However, hyperinsulinemia is observed in subjects with normoglycaemia and thus the paradigm above should be reevaluated. We describe two studies: MD-Lipolysis, a case control study investigating the mechanisms of obesity-driven insulin resistance by a systemic metabolic analysis, measurements of adipose tissue lipolysis by microdialysis, and adipose tissue genomics; and POEM, a cohort study used for validating differences in circulating metabolites in relation to adiposity and insulin resistance observed in the MD-Lipolysis study. In insulin-resistant obese with normal glycaemia from the MD-Lipolysis study, hyperinsulinemia was associated with elevated FFA. Lipolysis, assessed by glycerol release per adipose tissue mass or adipocyte surface, was similar between obese and lean individuals. Adipose tissue from obese subjects showed reduced expression of genes mediating catecholamine-driven lipolysis, lipid storage, and increased expression of genes driving hyperplastic growth. In the POEM study, FFA levels were specifically elevated in obese-overweight subjects with normal fasting glucose and high fasting levels of insulin and C-peptide. In obese subjects with normal glycaemia elevated circulating levels of FFA at fasting are the major metabolic derangement candidate driving fasting hyperinsulinemia. Elevated FFA in obese with normal glycaemia were better explained by increased fat mass rather than by adipose tissue insulin resistance. These results support the idea that hyperinsulinemia and insulin resistance may develop as part of a homeostatic adaptive response to increased adiposity and FFA. Swedish-Research-Council (2016-02660); Diabetesfonden (DIA2017-250; DIA2018-384; DIA2020-564); Novo-Nordisk-Foundation (NNF17OC0027458; NNF19OC0057174); Cancerfonden (CAN2017/472; 200840PjF); Swedish-ALF-agreement (2018-74560).
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影响因子：
82.9
作者：
Czech MP
通讯作者：
Czech MP
影响因子：
81.5
作者：
DeFronzo, Ralph A.;Ferrannini, Ele;Weiss, Ram
通讯作者：
Weiss, Ram
DOI：
10.1111/j.1475-097x.2009.00882.x
发表时间：
2009-09-01
影响因子：
1.8
作者：
Faizi, A. K.;Kornmo, D. W.;Agewall, S.
通讯作者：
Agewall, S.
影响因子：
56.9
作者：
Bachman, ES;Dhillon, H;Lowell, BB
通讯作者：
Lowell, BB
影响因子：
7.7
作者：
Gastaldelli, Amalia;Gaggini, Melania;DeFronzo, Ralph A.
通讯作者：
DeFronzo, Ralph A.