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  • Title: Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins.
    Author: Rämö JT, Kaye SM, Jukarainen S, Bogl LH, Hakkarainen A, Lundbom J, Lundbom N, Rissanen A, Kaprio J, Matikainen N, Pietiläinen KH.
    Journal: J Clin Endocrinol Metab; 2017 Jan 01; 102(1):220-231. PubMed ID: 27809652.
    Abstract:
    CONTEXT: The associations of body mass index (BMI) and liver fat (LF) with circulating prandial metabolomic markers are incompletely understood. OBJECTIVE: We aimed to characterize circulating metabolite excursions during an oral glucose tolerance test (OGTT) and evaluate whether the metabolomic signatures of BMI discordance coassociate with LF content. DESIGN, SETTING, AND PARTICIPANTS: We measured 80 metabolite parameters by nuclear magnetic resonance, together with glucose and insulin, during a 2-hour OGTT in 64 monozygotic (MZ) and 73 dizygotic (DZ) twin pairs (aged 22.8 to 36.2 years). Metabolite excursions during the OGTT were compared within BMI-discordant (intrapair difference, BMI ≥ 3 kg/m2) cotwins separately within MZ and DZ pairs. Insulin-based indices were calculated from the OGTT. LF was measured by magnetic resonance spectroscopy in 25 BMI-discordant MZ pairs. Metabolite profiles were compared with respect to LF discordance (ΔLF% ≥ 2%). RESULTS: We replicated many previously reported OGTT-induced metabolite excursions in all 274 individuals and report novel lipoprotein excursions. The associations between some metabolite excursions and BMI differed in MZ and DZ twins. In BMI-discordant MZ pairs (mean ΔBMI = 4.9 kg/m2) who were concordant for LF (Δ0.2%), few metabolites differed between the cotwins: very-low-density lipoprotein (VLDL) cholesterol and apolipoprotein B were elevated, and high-density lipoprotein size and concentration were decreased in the cotwins with higher BMI. In contrast, in BMI-discordant MZ pairs (ΔBMI = 6.1 kg/m2) who were discordant for LF (Δ6.8%), cotwins with higher BMI exhibited lower insulin sensitivity and widespread metabolomic differences: elevations in small VLDL and low-density lipoprotein particles, fatty acids (FAs), and isoleucine. Within all 64 MZ twin pairs, lower insulin sensitivity associated with higher levels of VLDLs, triglycerides, FAs, and isoleucine. CONCLUSIONS: BMI-discordant MZ twin pairs who also are discordant for LF have more pronounced within-pair differences in metabolomics profiles during an OGTT than BMI-discordant pairs without LF discordance.
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