TY - JOUR

T1 - Circulating Metabolomic and Lipidomic Signatures Identify a Type 2 Diabetes Risk Profile in Low-Birth-Weight Men with Non-Alcoholic Fatty Liver Disease

AU - Elingaard-Larsen, Line O.

AU - Villumsen, Sofie O.

AU - Justesen, Louise

AU - Thuesen, Anne Cathrine B.

AU - Kim, Min

AU - Ali, Mina

AU - Danielsen, Else R.

AU - Legido-Quigley, Cristina

AU - van Hall, Gerrit

AU - Hansen, Torben

AU - Ahluwalia, Tarunveer S.

AU - Vaag, Allan A.

AU - Brøns, Charlotte

N1 - Publisher Copyright: © 2023 by the authors.

PY - 2023

Y1 - 2023

N2 - The extent to which increased liver fat content influences differences in circulating metabolites and/or lipids between low-birth-weight (LBW) individuals, at increased risk of type 2 diabetes (T2D), and normal-birth-weight (NBW) controls is unknown. The objective of the study was to perform untargeted serum metabolomics and lipidomics analyses in 26 healthy, non-obese early-middle-aged LBW men, including five men with screen-detected and previously unrecognized non-alcoholic fatty liver disease (NAFLD), compared with 22 age- and BMI-matched NBW men (controls). While four metabolites (out of 65) and fifteen lipids (out of 279) differentiated the 26 LBW men from the 22 NBW controls (p ≤ 0.05), subgroup analyses of the LBW men with and without NAFLD revealed more pronounced differences, with 11 metabolites and 56 lipids differentiating (p ≤ 0.05) the groups. The differences in the LBW men with NAFLD included increased levels of ornithine and tyrosine (PFDR ≤ 0.1), as well as of triglycerides and phosphatidylcholines with shorter carbon-chain lengths and fewer double bonds. Pathway and network analyses demonstrated downregulation of transfer RNA (tRNA) charging, altered urea cycling, insulin resistance, and an increased risk of T2D in the LBW men with NAFLD. Our findings highlight the importance of increased liver fat in the pathogenesis of T2D in LBW individuals.

AB - The extent to which increased liver fat content influences differences in circulating metabolites and/or lipids between low-birth-weight (LBW) individuals, at increased risk of type 2 diabetes (T2D), and normal-birth-weight (NBW) controls is unknown. The objective of the study was to perform untargeted serum metabolomics and lipidomics analyses in 26 healthy, non-obese early-middle-aged LBW men, including five men with screen-detected and previously unrecognized non-alcoholic fatty liver disease (NAFLD), compared with 22 age- and BMI-matched NBW men (controls). While four metabolites (out of 65) and fifteen lipids (out of 279) differentiated the 26 LBW men from the 22 NBW controls (p ≤ 0.05), subgroup analyses of the LBW men with and without NAFLD revealed more pronounced differences, with 11 metabolites and 56 lipids differentiating (p ≤ 0.05) the groups. The differences in the LBW men with NAFLD included increased levels of ornithine and tyrosine (PFDR ≤ 0.1), as well as of triglycerides and phosphatidylcholines with shorter carbon-chain lengths and fewer double bonds. Pathway and network analyses demonstrated downregulation of transfer RNA (tRNA) charging, altered urea cycling, insulin resistance, and an increased risk of T2D in the LBW men with NAFLD. Our findings highlight the importance of increased liver fat in the pathogenesis of T2D in LBW individuals.

KW - lipidomics

KW - liver fat

KW - low-birth-weight

KW - metabolomics

KW - non-alcoholic fatty liver disease

KW - type 2 diabetes

U2 - 10.3390/nu15071590

DO - 10.3390/nu15071590

M3 - Journal article

C2 - 37049431

AN - SCOPUS:85152686729

VL - 15

JO - Nutrients

JF - Nutrients

SN - 2072-6643

IS - 7

M1 - 1590

ER -