TY - JOUR
T1 - The Relation between Adult Weight Gain, Adipocyte Volume, and the Metabolic Profile at Middle Age
AU - Verkouter, Inge
AU - Noordam, Raymond
AU - Loh, Nellie Y.
AU - van Dijk, Ko Willems
AU - Zock, Peter L.
AU - Mook-Kanamori, Dennis O.
AU - Le Cessie, Saskia
AU - Rosendaal, Frits R.
AU - Karpe, Fredrik
AU - Christodoulides, Costantinos
AU - de Mutsert, Renée
PY - 2021/11
Y1 - 2021/11
N2 - Context: Weight gain during adulthood increases cardiometabolic disease risk, possibly through adipocyte hypertrophy. Objective: We aimed to study the specific metabolomic profile of adult weight gain, and to examine its association with adipocyte volume. Methods: Nuclear magnetic resonance-based metabolomics were measured in the Netherlands Epidemiology of Obesity (NEO) study (n = 6347, discovery) and Oxford Biobank (n = 6317, replication). Adult weight gain was calculated as the absolute difference between body mass index (BMI) at middle age and recalled BMI at age 20 years. We performed linear regression analyses with both exposures BMI at age 20 years and weight gain, and separately with BMI at middle age in relation to 149 serum metabolomic measures, adjusted for age, sex, and multiple testing. Additionally, subcutaneous abdominal adipocyte biopsies were collected in a subset of the Oxford Biobank (n = 114) to estimate adipocyte volume. Results: Mean (SD) weight gain was 4.5 (3.7) kg/m2 in the NEO study and 3.6 (3.7) kg/m2 in the Oxford Biobank. Weight gain, and not BMI at age 20 nor middle age, was associated with concentrations of 7 metabolomic measures after successful replication, which included polyunsaturated fatty acids, small to medium low-density lipoproteins, and total intermediate-density lipoprotein. One SD weight gain was associated with 386 μm3 (95% CI, 143-629) higher median adipocyte volume. Adipocyte volume was associated with lipoprotein particles specific for adult weight gain. Conclusion: Adult weight gain is associated with specific metabolomic alterations of which the higher lipoprotein concentrations were likely contributed by larger adipocyte volumes, presumably linking weight gain to cardiometabolic disease.
AB - Context: Weight gain during adulthood increases cardiometabolic disease risk, possibly through adipocyte hypertrophy. Objective: We aimed to study the specific metabolomic profile of adult weight gain, and to examine its association with adipocyte volume. Methods: Nuclear magnetic resonance-based metabolomics were measured in the Netherlands Epidemiology of Obesity (NEO) study (n = 6347, discovery) and Oxford Biobank (n = 6317, replication). Adult weight gain was calculated as the absolute difference between body mass index (BMI) at middle age and recalled BMI at age 20 years. We performed linear regression analyses with both exposures BMI at age 20 years and weight gain, and separately with BMI at middle age in relation to 149 serum metabolomic measures, adjusted for age, sex, and multiple testing. Additionally, subcutaneous abdominal adipocyte biopsies were collected in a subset of the Oxford Biobank (n = 114) to estimate adipocyte volume. Results: Mean (SD) weight gain was 4.5 (3.7) kg/m2 in the NEO study and 3.6 (3.7) kg/m2 in the Oxford Biobank. Weight gain, and not BMI at age 20 nor middle age, was associated with concentrations of 7 metabolomic measures after successful replication, which included polyunsaturated fatty acids, small to medium low-density lipoproteins, and total intermediate-density lipoprotein. One SD weight gain was associated with 386 μm3 (95% CI, 143-629) higher median adipocyte volume. Adipocyte volume was associated with lipoprotein particles specific for adult weight gain. Conclusion: Adult weight gain is associated with specific metabolomic alterations of which the higher lipoprotein concentrations were likely contributed by larger adipocyte volumes, presumably linking weight gain to cardiometabolic disease.
KW - adipocyte volume
KW - body mass index
KW - cohort study
KW - metabolic profile
KW - metabolomics
KW - weight gain
U2 - 10.1210/clinem/dgab477
DO - 10.1210/clinem/dgab477
M3 - Article
C2 - 34181708
AN - SCOPUS:85119512344
SN - 0021-972X
VL - 106
SP - E4438-E4447
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -