Metabolomic Signatures of Sedentary Behavior and Cardiometabolic Traits in US Hispanics/Latinos: Results from HCHS/SOL, 2023, MOON et al.

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Metabolomic Signatures of Sedentary Behavior and Cardiometabolic Traits in US Hispanics/Latinos: Results from HCHS/SOL
Moon, Jee-Young;Chai, Jin Choul;Yu, Bing;Song, Rebecca J.;Chen, Guo-Chong;Graff, Mariaelisa;Daviglus, Martha L.;Chan, Queenie;Thyagarajan, Bharat;Castaneda, Sheila F.;Grove, Megan L.;Cai, Jianwen;Xue, Xiaonan;Mossavar-Rahmani, Yasmin;Vasan, Ramachandran S.;Boerwinkle, Eric;Kaplan, Robert C.;Qi, Qibin

Purpose: The aim of this study was to understand the serum metabolomic signatures of moderate-to-vigorous physical activity (MVPA) and sedentary behavior, and further associate their metabolomic signatures with incident cardiometabolic diseases.

Methods: This analysis included 2711 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 years (2008-11). An untargeted, liquid chromatography-mass spectrometry (LC-MS) was used to profile the serum metabolome. The associations of metabolites with accelerometer-measured MVPA and sedentary time were examined using survey linear regressions adjusting for covariates. The weighted correlation network analysis (WGCNA) identified modules of correlated metabolites in relation to sedentary time, and the modules were associated with incident diabetes, dyslipidemia, and hypertension over the 6-year follow up.

Results: Of 624 metabolites, five and 102 were associated with MVPA and sedentary behavior at FDR<0.05, respectively, after adjusting for socioeconomic and lifestyle factors. The WGCNA analysis identified 8 modules from 102 metabolites associated with sedentary time. Four modules (branched-chain amino acids [BCAA], erythritol, polyunsaturated fatty acid [PUFA], creatine) were positively, and the other four (acyl choline, plasmalogen GPC, plasmalogen GPE, urea cycle) were negatively correlated with sedentary time. Among these modules, a higher BCAA score and a lower plasmalogen GPC score were associated with increased risks of diabetes and dyslipidemia. A higher erythritol score was associated with increased risk of diabetes, and a lower acyl choline score was linked to increased risk of hypertension.

Conclusions: In this study of US Hispanics/Latinos, we identified multiple serum metabolomic signatures of sedentary behavior and their associations with risk of incident diabetes, hypertension, and dyslipidemia. These findings suggest a potential role of circulating metabolites in the links between sedentary behavior and cardiometabolic diseases.

Link | Paywalled (Medicine & Science in Sports & Exercise)

 

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HCHS/SOL is a prospective cohort study of 16,415 US Hispanic/Latino adults from randomly selected households through a multi-stage complex survey sampling design in four field centers (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA) with baseline clinic visits in 2008-2011 and second clinic visits in 2014-2017.

At baseline examination, all participants were asked to wear an accelerometer (Actical B1 version; model 198-0200-03; Respironics Co. Inc., Bend, Oregon) above the iliac crest for seven days, and to remove it during swimming, showering, and sleeping.

We considered 12,750 participants, satisfying an adherence criterion of at least 3 days of 10+ hours of wear time of accelerometer (18). To mitigate the influence of this selection bias in the analysis, inverse probability weighting was implemented accounting for non-adherent participants (2).

The serum metabolomic profiling was performed on 3,972 randomly selected participants at baseline by untargeted, liquid chromatography-mass spectrometry (LC-MS)-based protocol using DiscoveryHD4 platform [...] The platform identified 1136 metabolites, of which 782 metabolites were mapped to known metabolites. In our analysis, we considered 624 known metabolites with a missing rate of ≤20%. Missing values were imputed as 0.5 × minimum detected level and the inverse normal transformation was applied.

 

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Among 102 metabolites associated with sedentary time, 8 distinct sedentary metabolite modules were identified including BCAA, creatine, urea cycle/arginine metabolism, erythritol-related, PUFA, plasmalogen GPC, plasmalogen GPE, and acyl choline classes.

In a prospective analysis with median 6 years of follow-up, BCAA and plasmalogen GPC modules were associated with incident diabetes and dyslipidemia, erythritol module with incident diabetes, and acyl choline module with incident hypertension. Our findings suggest that there are multiple clusters of metabolites potentially altered by or correlated with sedentary behavior that may be related to the cardiometabolic disease risk separately.

Among a broad spectrum of 285 lipid metabolites, 48 were significantly associated with sedentary time. This included inverse associations with plasmalogens and acyl cholines, accompanied by an impact on cardiometabolic risk, and positive associations with PUFA.

An inverse association between sedentary time and acyl cholines in our study may be corroborated by a recent finding on reduced acyl cholines in patients with chronic fatigue syndrome (ME/CFS) (33), who may have prolonged sedentary time.

(33) is Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids (2020, Metabolites)

Our study supports that activation of BCAA catabolism, especially isoleucine and its derivatives in the pathway, was associated with prolonged sedentary time rather than MVPA, which in turn was associated with increased diabetes and dyslipidemia.

As an observational study, our data are not designed to distinguish between metabolites that might result from an individual’s activity habits, and those that instead may be associated with reduced movement because they are linked with neurological, musculoskeletal, or energetic functions. We are unable to determine whether the metabolomic changes found in sedentary persons may be mediated by sedentarism per se, or by sedentary time’s displacement of either low- or high-intensity activity. All the cross-sectional associations could be bi-directional.