The effect of long-term exposure to moderate high altitude on adipokines and insulin sensitivity

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2025-01-01 DOI:10.1016/j.cyto.2024.156823
Wenxia Wu , Guishan Chen , Xiaoyun Zhang , Hongshi Wu , Yu-E Wang , Xin Li , Ying Liang , Dan Liu
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Abstract

Background

High altitude area refers to plateau area with an altitude of 1500 m or above. Short-term (less than 30 days) exposure to high-altitude environments (hypoxia, low temperature, low pressure) might affect the adipokines level and insulin sensitivity. However, whether long-term exposure to moderate high altitude would have an impact on adipokines and insulin sensitivity remains unknown.

Objective

This study aimed to explore the effect of long-term exposure (12 months) to moderate high altitudes (2900 m) on changes in adipokines level and insulin sensitivity.

Methods

48 healthy adults from Guangdong Province (the average altitude less than 50 m) to Nyingchi (an average altitude of 2900 m) were included with follow-up of 12 months. Before entering Nyingchi, baseline anthropometric indicators (height, weight, blood pressure), metabolic indicators: fasting plasma glucose (FPG), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR), adipokines: adiponectin and leptin, inflammatory indicators: tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6); hypoxia-inducible factor 1alpha (HIF-1α), oxidative stress indicator: malondialdehyde (MDA), antioxidant indicators: superoxide dismutase (SOD) and glutathione (GSH) were determined. After entering Nyingchi, the above indicators were retested at the 1st, 6th, and 12th month. The control group consist of 47 local residents in Nyingchi. Linear mixed effect model was used to analyze the trend of index changes. Multivariate linear regression analysis was analyzed to explore the influence factors of adiponectin at 12th month.

Results

After 12 months exposure to high altitude, the body mass index (BMI), systolic blood pressure (SBP) and FPG of subjects decreased from baseline of 23.51 ± 2.68 kg/m2, 123.68 ± 14.94 mmHg and 5.05 ± 0.36 mmol/L to 22.59 ± 2.56 kg/m2, 116.10 ± 14.68 mmHg and 4.65 ± 0.46 mmol/L respectively, HDL-C increased from baseline of 1.30 ± 0.26 mmol/L to 1.37 ± 0.30 mmol/L. HOMA-IR decreased from baseline 1.70 (1.19, 2.22) to 1.25(1.04, 1.78). Adiponectin increased from 3.85(3.05, 4.98) to 4.75(3.33, 5.88) μg/mL, leptin decreased from 1022.10(496.30, 2508.60) to 729.60(308.78, 1670.20) pg/mL. TNFα decreased from 6.81(5.37, 8.49) to 5.50(4.00, 6.74) pg/mL. The level of HIF-1α increased from baseline 1.91 (1.32, 5.09) to 2.94 (1.65, 15.45) pg/mL. SOD increased from 0.20(0.15, 0.24) to 0.25(0.20, 0.28) U/mL. Multivariate linear regression analysis showed that HIF-1α (β = 0.006, 95 %CI, 0.001–0.012, p = 0.033) and SOD (β = 7.318, 95 %CI, 0.486–14.149, p = 0.037) was the factors that influenced adiponectin level at 12th month after exposure to high altitude.

Conclusion

Long-term exposure to moderate high-altitude environments could improve insulin sensitivity and adipocyte function in healthy adults. Elevated HIF-1α and SOD during altitude acclimatization were the beneficial factors for improvement of adipocyte function. It is worthwhile to further explore the effect and the potential therapeutic value of long-term moderate altitude exposure on adults with metabolic disorders.

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中高海拔长期暴露对脂肪因子和胰岛素敏感性的影响。
背景:高海拔地区是指海拔1500米及以上的高原地区。短期(少于30天)暴露于高海拔环境(缺氧、低温、低压)可能会影响脂肪因子水平和胰岛素敏感性。然而,长期暴露在中等高海拔地区是否会对脂肪因子和胰岛素敏感性产生影响尚不清楚。目的:本研究旨在探讨长期(12个月)暴露于中等高海拔地区(2900米)对脂肪因子水平和胰岛素敏感性变化的影响。方法:选取广东省(平均海拔小于50 m)至林芝(平均海拔2900 m)地区48例健康成人,随访12个月。进入林芝前,基线人体测量指标(身高、体重、血压),代谢指标:空腹血糖(FPG)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、胰岛素抵抗指数(HOMA-IR),脂肪因子:脂联素、瘦素,炎症指标:肿瘤坏死因子α (TNFα)、白细胞介素-6 (IL-6);测定低氧诱导因子1α (HIF-1α)、氧化应激指标丙二醛(MDA)、抗氧化指标超氧化物歧化酶(SOD)和谷胱甘肽(GSH)。进入林芝后,于第1、6、12个月复查上述指标。对照组由47名林芝当地居民组成。采用线性混合效应模型分析指标变化趋势。采用多元线性回归分析探讨12个月时脂联素的影响因素。结果:高原暴露12个月后,受试者体重指数(BMI)、收缩压(SBP)和FPG分别由基线水平23.51±2.68 kg/m2、123.68±14.94 mmHg和5.05±0.36 mmol/L降至22.59±2.56 kg/m2、116.10±14.68 mmHg和4.65±0.46 mmol/L, HDL-C由基线水平1.30±0.26 mmol/L上升至1.37±0.30 mmol/L。HOMA-IR从基线1.70(1.19,2.22)降至1.25(1.04,1.78)。脂联素由3.85(3.05,4.98)上升至4.75(3.33,5.88)μg/mL,瘦素由1022.10(496.30,2508.60)下降至729.60(308.78,1670.20)pg/mL。TNFα从6.81(5.37,8.49)pg/mL降至5.50(4.00,6.74)pg/mL。HIF-1α水平从基线1.91(1.32,5.09)增加到2.94 (1.65,15.45)pg/mL。SOD由0.20(0.15,0.24)U/mL升高至0.25(0.20,0.28)U/mL。多因素线性回归分析显示,HIF-1α (β = 0.006, 95% CI, 0.001 ~ 0.012, p = 0.033)和SOD (β = 7.318, 95% CI, 0.486 ~ 14.149, p = 0.037)是影响高原暴露12个月后脂联素水平的因素。结论:长期暴露于中等高海拔环境可改善健康成人的胰岛素敏感性和脂肪细胞功能。高原适应过程中HIF-1α和SOD的升高是脂肪细胞功能改善的有利因素。长期中等海拔暴露对成人代谢性疾病的影响及其潜在的治疗价值值得进一步探讨。
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来源期刊
Cytokine
Cytokine 医学-免疫学
CiteScore
7.60
自引率
2.60%
发文量
262
审稿时长
48 days
期刊介绍: The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.
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