Wu Wenxia, Chen Guishan, Zhang Xiaoyun, Wu Hongshi, Wang Yu-E, Li Xin, Liang Ying, Liu Dan
Department of General Practice, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of General Practice, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Shanwei, 516600, China.
Endocrinology and Metabolism Department, The First Affiliated Hospital of Shantou University Medical College, Shantou University, Shantou, 515000, China.
Cytokine. 2025 Jan;185:156823. doi: 10.1016/j.cyto.2024.156823. Epub 2024 Dec 2.
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.
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.
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.
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/m, 123.68 ± 14.94 mmHg and 5.05 ± 0.36 mmol/L to 22.59 ± 2.56 kg/m, 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.
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.
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，长期暴露于中度高海拔是否会对脂肪因子和胰岛素敏感性产生影响仍不清楚。
本研究旨在探讨长期（12个月）暴露于中度高海拔（2900米）对脂肪因子水平变化和胰岛素敏感性的影响。
纳入48名从广东省（平均海拔低于50米）到林芝（平均海拔2900米）的健康成年人，进行为期12个月的随访。在进入林芝之前，测定基线人体测量指标（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：脂联素和瘦素、炎症指标：肿瘤坏死因子α（TNFα）和白细胞介素-6（IL-6）；缺氧诱导因子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，在第1、6和12个月重新检测上述指标。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第12个月脂联素的影响因素。
暴露于高海拔12个月后，受试者的体重指数（BMI）、收缩压（SBP）和FPG分别从基线的23.51±2.68kg/m、123.68±14.94mmHg和5.05±0.36mmol/L降至22.59±2.56kg/m、116.10±14.68mmHg和4.65±0.46mmol/L，HDL-C从基线的1.30±0.26mmol/L升至1.37±0.30mmol/L。HOMA-IR从基线的1.70（1.19，2.22）降至1.25（1.04，1.78）。脂联素从3.85（3.05，4.98）升至4.75（3.33，5.88）μg/mL，瘦素从1022.10（496.30，2508.60）降至729.60（308.78，1670.20）pg/mL。TNFα从6.81（5.37，8.49）降至5.50（4.00，6.74）pg/mL。HIF-1α水平从基线的1.91（1.32，5.09）升至2.94（1.65，15.45）pg/mL。SOD从0.20（0.15，0.24）升至0.25（0.20，0.28）U/mL。多元线性回归分析显示，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）是暴露于高海拔12个月后影响脂联素水平的因素。
长期暴露于中度高海拔环境可改善健康成年人的胰岛素敏感性和脂肪细胞功能。海拔适应过程中HIF-1α和SOD的升高是改善脂肪细胞功能的有益因素。进一步探索长期中度海拔暴露对代谢紊乱成年人的影响及潜在治疗价值是值得的。
