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

Elingaard-Larsen, Line O. ; Villumsen, Sofie O. ; Justesen, Louise ; Thuesen, Anne Cathrine B. ; Kim, Min ; Ali, Mina ; Danielsen, Else R. ; Legido-Quigley, Cristina ; van Hall, Gerrit and Hansen, Torben , et al. (2023) In Nutrients 15(7).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
lipidomics, liver fat, low-birth-weight, metabolomics, non-alcoholic fatty liver disease, type 2 diabetes
in
Nutrients
volume
15
issue
7
article number
1590
publisher
MDPI AG
external identifiers
  • pmid:37049431
  • scopus:85152686729
ISSN
2072-6643
DOI
10.3390/nu15071590
language
English
LU publication?
yes
id
0120c14c-1e4a-4391-9da9-4ed82599d366
date added to LUP
2023-08-07 11:50:57
date last changed
2024-04-20 00:10:24
@article{0120c14c-1e4a-4391-9da9-4ed82599d366,
  abstract     = {{<p>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 (P<sub>FDR</sub> ≤ 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.</p>}},
  author       = {{Elingaard-Larsen, Line O. and Villumsen, Sofie O. and Justesen, Louise and Thuesen, Anne Cathrine B. and Kim, Min and Ali, Mina and Danielsen, Else R. and Legido-Quigley, Cristina and van Hall, Gerrit and Hansen, Torben and Ahluwalia, Tarunveer S. and Vaag, Allan A. and Brøns, Charlotte}},
  issn         = {{2072-6643}},
  keywords     = {{lipidomics; liver fat; low-birth-weight; metabolomics; non-alcoholic fatty liver disease; type 2 diabetes}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{MDPI AG}},
  series       = {{Nutrients}},
  title        = {{Circulating Metabolomic and Lipidomic Signatures Identify a Type 2 Diabetes Risk Profile in Low-Birth-Weight Men with Non-Alcoholic Fatty Liver Disease}},
  url          = {{http://dx.doi.org/10.3390/nu15071590}},
  doi          = {{10.3390/nu15071590}},
  volume       = {{15}},
  year         = {{2023}},
}