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Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression

Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression
Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression
Nonalcoholic fatty liver disease (NAFLD) describes an increasingly prevalent spectrum of liver disorders associated with obesity and metabolic syndrome. It is uncertain why steatosis occurs in some individuals, whereas nonalcoholic steatohepatitis (NASH) occurs in others. We have generated a novel mouse model to test our hypothesis: that maternal fat intake contributes to the development of NAFLD in adult offspring. Female mice were fed either a high-fat (HF) or control chow (C) diet before and during gestation and lactation. Resulting offspring were fed either a C or a HF diet after weaning, to generate four offspring groups; HF/HF, HF/C, C/HF, C/C. At 15 weeks of age, liver histology was normal in both the C/C and HF/C offspring. Kleiner scoring showed that although the C/HF offspring developed nonalcoholic fatty liver, the HF/HF offspring developed NASH. At 30 weeks, histological analysis and Kleiner scoring showed that both the HF/C and C/HF groups had NAFLD, whereas the HF/HF had a more severe form of NASH. Therefore, exposure to a HF diet in utero and during lactation contributes toward NAFLD progression. We investigated the mechanisms by which this developmental priming is mediated. At 15 weeks of age, hepatic mitochondrial electron transport chain (ETC) enzyme complex activity (I, II/III, and IV) was reduced in both groups of offspring from HF-fed mothers (HF/C and HF/HF). In addition, measurement of hepatic gene expression indicated that lipogenesis, oxidative stress, and inflammatory pathways were up-regulated in the 15-week-old HF/C and HF/HF offspring. Conclusion: Maternal fat intake contributes toward the NAFLD progression in adult offspring, which is mediated through impaired hepatic mitochondrial metabolism and up-regulated hepatic lipogenesis
0270-9139
1796-1808
Bruce, Kimberley D.
2065fe20-0e9e-4f1a-8463-71b832776fa1
Cagampang, Felino R.
7cf57d52-4a65-4554-8306-ed65226bc50e
Argenton, Marco
3c37b8be-012d-4d15-9276-cd0a9d77f825
Zhang, Junlong
68a8fa77-c5db-4b34-aa9a-fbad6860155f
Ethirajan, Priya L.
dfad4a1d-7f2f-415b-a496-3cbf7e233031
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Bateman, Adrian C.
28ae82e3-b93a-429a-81f5-04e8f1ff4cc7
Clough, Geraldine F.
9f19639e-a929-4976-ac35-259f9011c494
Poston, Lucilla
916aced2-462e-445f-9efa-83ed4b7b3a9f
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
McConnell, Josie M.
a072acaa-3010-4031-8bd3-3f993c713a8f
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Bruce, Kimberley D.
2065fe20-0e9e-4f1a-8463-71b832776fa1
Cagampang, Felino R.
7cf57d52-4a65-4554-8306-ed65226bc50e
Argenton, Marco
3c37b8be-012d-4d15-9276-cd0a9d77f825
Zhang, Junlong
68a8fa77-c5db-4b34-aa9a-fbad6860155f
Ethirajan, Priya L.
dfad4a1d-7f2f-415b-a496-3cbf7e233031
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Bateman, Adrian C.
28ae82e3-b93a-429a-81f5-04e8f1ff4cc7
Clough, Geraldine F.
9f19639e-a929-4976-ac35-259f9011c494
Poston, Lucilla
916aced2-462e-445f-9efa-83ed4b7b3a9f
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
McConnell, Josie M.
a072acaa-3010-4031-8bd3-3f993c713a8f
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c

Bruce, Kimberley D., Cagampang, Felino R., Argenton, Marco, Zhang, Junlong, Ethirajan, Priya L., Burdge, Graham C., Bateman, Adrian C., Clough, Geraldine F., Poston, Lucilla, Hanson, Mark A., McConnell, Josie M. and Byrne, Christopher D. (2009) Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression. Hepatology, 50 (6), 1796-1808. (doi:10.1002/hep.23205).

Record type: Article

Abstract

Nonalcoholic fatty liver disease (NAFLD) describes an increasingly prevalent spectrum of liver disorders associated with obesity and metabolic syndrome. It is uncertain why steatosis occurs in some individuals, whereas nonalcoholic steatohepatitis (NASH) occurs in others. We have generated a novel mouse model to test our hypothesis: that maternal fat intake contributes to the development of NAFLD in adult offspring. Female mice were fed either a high-fat (HF) or control chow (C) diet before and during gestation and lactation. Resulting offspring were fed either a C or a HF diet after weaning, to generate four offspring groups; HF/HF, HF/C, C/HF, C/C. At 15 weeks of age, liver histology was normal in both the C/C and HF/C offspring. Kleiner scoring showed that although the C/HF offspring developed nonalcoholic fatty liver, the HF/HF offspring developed NASH. At 30 weeks, histological analysis and Kleiner scoring showed that both the HF/C and C/HF groups had NAFLD, whereas the HF/HF had a more severe form of NASH. Therefore, exposure to a HF diet in utero and during lactation contributes toward NAFLD progression. We investigated the mechanisms by which this developmental priming is mediated. At 15 weeks of age, hepatic mitochondrial electron transport chain (ETC) enzyme complex activity (I, II/III, and IV) was reduced in both groups of offspring from HF-fed mothers (HF/C and HF/HF). In addition, measurement of hepatic gene expression indicated that lipogenesis, oxidative stress, and inflammatory pathways were up-regulated in the 15-week-old HF/C and HF/HF offspring. Conclusion: Maternal fat intake contributes toward the NAFLD progression in adult offspring, which is mediated through impaired hepatic mitochondrial metabolism and up-regulated hepatic lipogenesis

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e-pub ahead of print date: 5 August 2009
Published date: December 2009
Organisations: Dev Origins of Health & Disease

Identifiers

Local EPrints ID: 72612
URI: https://eprints.soton.ac.uk/id/eprint/72612
ISSN: 0270-9139
PURE UUID: e3020a49-13de-4a24-a19d-566fc831eec0
ORCID for Felino R. Cagampang: ORCID iD orcid.org/0000-0003-4404-9853
ORCID for Graham C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967
ORCID for Geraldine F. Clough: ORCID iD orcid.org/0000-0002-6226-8964
ORCID for Mark A. Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 18 Feb 2010
Last modified: 11 Dec 2018 01:34

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