Causal links between obesity, lipids, adipokines, and cognition: a bidirectional Mendelian-randomization analysis.

IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Frontiers in Endocrinology Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI:10.3389/fendo.2025.1439341
Meng Gong, Haichao Liu, Zhixiang Liu, Yongshen Wang, Shiyi Qi, Hong Guo, Song Jin
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Abstract

Background: The aim of this study was to explore the genetic level association between obesity, lipids, adipokines, and cognitive ability using bidirectional Mendelian randomization (MR) strategies.

Methods: Summary data for three obesity indicators [body mass index (BMI), body fat percentage (BFP) and waist-hip ratio (WHR)], three lipid indicators [HDL cholesterol (HDL), LDL cholesterol (LDL) and triglycerides (TG)], three adipokines [circulating leptin (LEP), Agouti-related protein (AgRP) and Adiponectin (APDN)], and four cognitive ability indicators [cognitive function (CF), cognitive performance (CP), simple reaction time (SRT) and fluid intelligence score (FIS)] were collected. Bidirectional inverse-variance weighted Mendelian randomization (MR) was employed to evaluate the relationship between adiposity and cognitive function. We employed genetic instruments for adiposity indicators as exposures in one direction, and repeated the analysis in the opposite direction using instruments for cognitive function. Sensitivity analyses were conducted to explore heterogeneity and potential horizontal pleiotropy.

Results: Genetically predicted adiposity showed robust associations with markers of cognitive ability. Higher genetically predicted obesity indicators (such as BMI, BFP and WHR), and lipid and adipokineslevels (such as HDL and AgRP) with reduced cognitive ability indicators (such as CF and CP). In the opposite direction, FIS and SRT may influence BMI and HDL respectively. MR estimates for the effects of cognition ability on all obesity, lipids and adipokines measures indicated worse FIS and SRT were associated with higher BMI and lower HDL.

Conclusions: Our MR reveals that high BMI, BFP, WHR and AgRP have negative causal direct effects with cognitive ability, while high HDL and ADPN have positive causal direct effects with cognitive ability. For the reverse causal direction, our consistent findings that worse cognitive function such as SRT and FIS may influence serum HDL level and BMI.

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肥胖、脂质、脂肪因子与认知之间的因果关系:双向孟德尔随机化分析。
背景:本研究的目的是利用双向孟德尔随机化(MR)策略探讨肥胖、脂质、脂肪因子和认知能力之间的遗传水平关联。方法:收集3项肥胖指标[体重指数(BMI)、体脂率(BFP)和腰臀比(WHR)], 3项脂质指标[HDL胆固醇(HDL)、LDL胆固醇(LDL)和甘油三酯(TG)], 3项脂肪因子[循环瘦素(LEP)、agouti相关蛋白(AgRP)和脂联素(APDN)], 4项认知能力指标[认知功能(CF)、认知表现(CP)、简单反应时间(SRT)和体液智力评分(FIS)]的汇总数据。采用双向反方差加权孟德尔随机化(MR)来评估肥胖与认知功能的关系。我们在一个方向上使用肥胖指标的遗传工具,并在相反的方向上使用认知功能的工具重复分析。进行敏感性分析以探索异质性和潜在的水平多效性。结果:基因预测的肥胖与认知能力的标记有很强的相关性。较高的基因预测肥胖指标(如BMI、BFP和WHR)和脂质和脂肪因子水平(如HDL和AgRP)与认知能力指标(如CF和CP)降低。相反,FIS和SRT可能分别影响BMI和HDL。认知能力对所有肥胖、脂质和脂肪因子测量的影响的MR估计表明,较差的FIS和SRT与较高的BMI和较低的HDL相关。结论:MR结果显示,高BMI、BFP、WHR和AgRP对认知能力有负向直接因果影响,而高HDL和ADPN对认知能力有正向直接因果影响。对于相反的因果方向,我们一致的发现,较差的认知功能,如SRT和FIS可能会影响血清HDL水平和BMI。
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来源期刊
Frontiers in Endocrinology
Frontiers in Endocrinology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
5.70
自引率
9.60%
发文量
3023
审稿时长
14 weeks
期刊介绍: Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series. In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology. Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.
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