Table 4.
Direct and Indirect Effects (Mediated Through Body Mass Index) of Physical Activity on Metabolite Levels in Samples of Participants From the Nurses’ Health Study (1989–1990), Nurses’ Health Study II (1996–1999), and the Health Professionals Follow-up Study (1993–1995)a
| Metabolite | HMDB ID | Effect, β (SE) (×10−3) | % of Effect Mediated by BMI | ||
|---|---|---|---|---|---|
| Direct Effect | Indirect Effect (Mediated by BMIb) | Total Effect | |||
| Cholesteryl esters | |||||
| C18:2 CE | HMDB00610 | 4.66 (0.79) | 0.52 (0.11) | 5.18 (0.79) | 9.98 |
| C18:1 CE | HMDB00918 | 3.02 (0.79) | 0.48 (0.11) | 3.49 (0.79) | 13.68 |
| C16:0 CE | HMDB00885 | 2.84 (0.79) | 0.45 (0.10) | 3.29 (0.79) | 13.57 |
| C18:3 CE | HMDB10370 | 2.84 (0.81) | −0.14 (0.09) | 2.70 (0.81) | −5.14c |
| C22:4 CE | HMDB06729 | 2.69 (1.29) | 0.84 (0.16) | 3.53 (1.28) | 23.89 |
| Phospholipids | |||||
| C18:2 LPC | HMDB10386 | 4.46 (0.80) | 0.58 (0.12) | 5.04 (0.80) | 11.44 |
| C20:5 LPC | HMDB10397 | 3.82 (0.81) | 0.39 (0.10) | 4.22 (0.81) | 9.30 |
| C18:1 LPC | HMDB02815 | 3.61 (0.80) | 0.52 (0.11) | 4.13 (0.80) | 12.60 |
| C36:4 PC-A | HMDB07983 | 4.48 (0.81) | 0.22 (0.09) | 4.70 (0.81) | 4.76 |
| C34:3 PC plasmalogen | HMDB11211 | 3.89 (0.80) | 0.48 (0.11) | 4.37 (0.80) | 11.02 |
| C36:3 PC plasmalogen | HMDB11244 | 3.36 (0.79) | 0.57 (0.11) | 3.93 (0.79) | 14.54 |
| C36:2 PC plasmalogen | HMDB11243 | 2.90 (0.78) | 0.57 (0.11) | 3.47 (0.78) | 16.42 |
| C34:2 PC plasmalogen | HMDB11210 | 2.83 (0.78) | 0.57 (0.11) | 3.40 (0.78) | 16.63 |
| C36:0 PC | HMDB08036 | 2.91 (0.81) | 0.18 (0.09) | 3.08 (0.81) | 5.68 |
| C18:2 LPE | HMDB11507 | 2.91 (0.70) | 0.22 (0.08) | 3.12 (0.70) | 6.95 |
| C18:1 LPE | HMDB11506 | 2.70 (0.71) | 0.22 (0.08) | 2.92 (0.70) | 7.58 |
| C38:3 PE plasmalogen | HMDB11384 | 2.75 (0.78) | 0.51 (0.11) | 3.26 (0.78) | 15.78 |
| C40:6 PE | HMDB09012 | −2.61 (0.78) | −0.38 (0.10) | −2.99 (0.78) | 12.62c |
| C38:2 PE | HMDB08942 | 2.41 (0.81) | 0.35 (0.10) | 2.76 (0.81) | 12.76 |
| C34:0 PI | HMDB09805 | 3.83 (0.81) | −0.14 (0.09) | 3.68 (0.81) | −3.88c |
| Glycerolipids | |||||
| C34:3 DG | HMDB07132 | −2.59 (0.80) | −0.79 (0.13) | −3.39 (0.80) | 23.36 |
| C34:2 DG | HMDB07103 | −2.36 (0.79) | −0.84 (0.14) | −3.20 (0.80) | 26.33 |
| C32:1 DG | HMDB07099 | −2.23 (0.79) | −0.84 (0.14) | −3.07 (0.79) | 27.40 |
| C34:1 DG | HMDB07102 | −2.16 (0.79) | −0.87 (0.14) | −3.03 (0.79) | 28.71 |
| C32:0 DG | HMDB07098 | −2.03 (0.79) | −0.84 (0.14) | −2.87 (0.79) | 29.37 |
| C50:2 TG | HMDB05377 | −2.31 (0.78) | −0.86 (0.14) | −3.17 (0.79) | 27.18 |
| C52:2 TG | HMDB05369 | −2.19 (0.79) | −0.86 (0.14) | −3.05 (0.80) | 28.15 |
| C50:3 TG | HMDB05433 | −2.11 (0.79) | −0.81 (0.14) | −2.92 (0.80) | 27.73 |
| C50:1 TG | HMDB05360 | −1.91 (0.78) | −0.89 (0.14) | −2.79 (0.79) | 31.74 |
| Sphingolipids | |||||
| C18 carnitine | HMDB00848 | 1.67 (0.57) | 0.33 (0.07) | 2.00 (0.56) | 16.31 |
| Amino acids | |||||
| Glycine | HMDB00123 | 1.89 (0.56) | 0.71 (0.11) | 2.60 (0.57) | 27.33 |
| Citrulline | HMDB00904 | 1.90 (0.55) | 0.27 (0.07) | 2.16 (0.55) | 12.28 |
| Glutamate | HMDB00148 | −1.34 (0.56) | −0.84 (0.12) | −2.19 (0.57) | 38.65 |
| Asparagine | HMDB00168 | 1.43 (0.57) | 0.46 (0.09) | 1.89 (0.57) | 24.25 |
| Others | |||||
| 1-Methyladenosine | HMDB03331 | −2.24 (0.56) | −0.77 (0.12) | −3.02 (0.56) | 25.69 |
| Creatine | HMDB00064 | −1.60 (0.57) | −0.41 (0.08) | −2.01 (0.57) | 20.31 |
Abbreviations: BMI, body mass index; CE, cholesteryl ester; DG, diglyceride; HMDB, Human Metabolome Database; ID, identification number; LPC, lysophosphatidylcholines; LPE, lysophosphatidylethanolamine; PC, phosphocholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; SE, standard error; TG, triglyceride.
a Linear regression analysis with adjustment for age (years; continuous), case-control status (case, control), case-control study nested within the 3 cohort studies (16 categories), smoking status (never, past, or current smoker), fasting status at blood collection (yes, no), alcohol intake (g/day; continuous), Alternative Healthy Eating Index score (0–100; continuous), total energy intake (kcal/day; continuous), and intakes of fatty acids (linolenic acid, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid, stearic acid, and trans- fatty acids).
b BMI is calculated as weight (kg)/height (m)2.
c The mediation effect was not significant.