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Exposure to a high fat, and low carbohydrate diet in utero and during lactation modulates hepatic mitochondrial complex activity

Exposure to a high fat, and low carbohydrate diet in utero and during lactation modulates hepatic mitochondrial complex activity
Exposure to a high fat, and low carbohydrate diet in utero and during lactation modulates hepatic mitochondrial complex activity
Evidence suggests that altered maternal nutrition increases susceptibility to the metabolic syndrome in adult offspring. An increase in the prevalence of metabolic syndrome has been linked to an increase in incidence of non-alcoholic fatty liver disease (NAFLD), which can range from fatty liver (steatosis), to non-alcoholic steatohepatitis (NASH) and fibrosis. Since mitochondrial dysfunction impairs fatty liver homeostasis, increases reactive oxygen species and triggers lipid peroxidation mitochondrial dysfunction it is a likely candidate for NAFLD disease progression. To investigate the effect of maternal nutrition on mitochondrial dysfunction and development of NASH, we determined changes in electron transport chain (ETC) enzyme complex activity in liver tissue from mouse offspring that were exposed to a high fat or control diet both pre and post-natally Female C57 BL/6J black mice were randomly assigned to either a high fat diet (HF- 45% kcal fat, 20% kcal protein, 35% kcal carbohydrate, n =10) or standard laboratory chow diet (C- 21% kcal fat, 18% kcal protein, 63% kcal carbohydrate, n = 10). Dams were fed 4 weeks prior to conception, during gestation and lactation. At weaning the offspring were assigned either HF or C diet, generating 4 experimental groups: HF/HF (n= 12), HF/C (n = 12), C/HF (n = 12), C/C (n = 12), which represents prenatal/postnatal diet respectively. Offspring food intake and weights were recorded at weekly intervals. Locomotor activity and blood pressure was measured at 13 weeks of age. At 15 weeks offspring were killed and tissues were weighed and collected. Hepatic mitochondrial complex (I, II/III, and IV) activity was measured by spectrophotometer following addition of relevant cofactors (rotenone, antimycin reduced cytochrome c respectively). Results were standardized using citrate synthetase activity. Histological analysis of liver specimens stained with haematoxylin and eosin (H and E) were used to determine levels of steatosis. In liver tissue from both the HF/C and HF/HF offspring mitochondrial complex I, II/III and IV activity was significantly reduced when compared to both the C/C and C/HF (p < 0.05) groups. The greatest decrease was observed with Complex I, where a 3.2 and 3.7-fold reduction in activity levels were seen HF/HF offspring (p < 0.05) and HF/C offspring (p < 0.05) respectively, compared to C/C offspring. This data implies that the pre-natal exposure to a HF diet impairs complex activity and mitochondrial function. Steatosis was visible in liver sections from C/HF and HF/HF animals, and there was an inflammatory infiltrate in sections from the HF/HF group. This data provides preliminary evidence to suggest that exposure to a HF diet in utero may contribute to disease progression of NASH.
lactation, activity, exposure, diet, in-utero
Bruce, K.D.
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Argenton, M.
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Cagampang, F.
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McConnell, J.
bbfe2d9b-afe1-436d-bd36-ceb05313e6c8
Poston, L.
7503d11e-bc6a-4925-b622-bf2937ab1722
Hanson, M.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Byrne, C.
1370b997-cead-4229-83a7-53301ed2a43c
Bruce, K.D.
1ded890b-addf-45bd-ba59-dbaedaeee931
Argenton, M.
c2fb58b7-f323-4d46-a39e-a343cb680abc
Cagampang, F.
7cf57d52-4a65-4554-8306-ed65226bc50e
McConnell, J.
bbfe2d9b-afe1-436d-bd36-ceb05313e6c8
Poston, L.
7503d11e-bc6a-4925-b622-bf2937ab1722
Hanson, M.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Byrne, C.
1370b997-cead-4229-83a7-53301ed2a43c

Bruce, K.D., Argenton, M., Cagampang, F., McConnell, J., Poston, L., Hanson, M. and Byrne, C. (2008) Exposure to a high fat, and low carbohydrate diet in utero and during lactation modulates hepatic mitochondrial complex activity. Proceedings of the Physiological Society, 11 (C108).

Record type: Article

Abstract

Evidence suggests that altered maternal nutrition increases susceptibility to the metabolic syndrome in adult offspring. An increase in the prevalence of metabolic syndrome has been linked to an increase in incidence of non-alcoholic fatty liver disease (NAFLD), which can range from fatty liver (steatosis), to non-alcoholic steatohepatitis (NASH) and fibrosis. Since mitochondrial dysfunction impairs fatty liver homeostasis, increases reactive oxygen species and triggers lipid peroxidation mitochondrial dysfunction it is a likely candidate for NAFLD disease progression. To investigate the effect of maternal nutrition on mitochondrial dysfunction and development of NASH, we determined changes in electron transport chain (ETC) enzyme complex activity in liver tissue from mouse offspring that were exposed to a high fat or control diet both pre and post-natally Female C57 BL/6J black mice were randomly assigned to either a high fat diet (HF- 45% kcal fat, 20% kcal protein, 35% kcal carbohydrate, n =10) or standard laboratory chow diet (C- 21% kcal fat, 18% kcal protein, 63% kcal carbohydrate, n = 10). Dams were fed 4 weeks prior to conception, during gestation and lactation. At weaning the offspring were assigned either HF or C diet, generating 4 experimental groups: HF/HF (n= 12), HF/C (n = 12), C/HF (n = 12), C/C (n = 12), which represents prenatal/postnatal diet respectively. Offspring food intake and weights were recorded at weekly intervals. Locomotor activity and blood pressure was measured at 13 weeks of age. At 15 weeks offspring were killed and tissues were weighed and collected. Hepatic mitochondrial complex (I, II/III, and IV) activity was measured by spectrophotometer following addition of relevant cofactors (rotenone, antimycin reduced cytochrome c respectively). Results were standardized using citrate synthetase activity. Histological analysis of liver specimens stained with haematoxylin and eosin (H and E) were used to determine levels of steatosis. In liver tissue from both the HF/C and HF/HF offspring mitochondrial complex I, II/III and IV activity was significantly reduced when compared to both the C/C and C/HF (p < 0.05) groups. The greatest decrease was observed with Complex I, where a 3.2 and 3.7-fold reduction in activity levels were seen HF/HF offspring (p < 0.05) and HF/C offspring (p < 0.05) respectively, compared to C/C offspring. This data implies that the pre-natal exposure to a HF diet impairs complex activity and mitochondrial function. Steatosis was visible in liver sections from C/HF and HF/HF animals, and there was an inflammatory infiltrate in sections from the HF/HF group. This data provides preliminary evidence to suggest that exposure to a HF diet in utero may contribute to disease progression of NASH.

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More information

Published date: 2008
Keywords: lactation, activity, exposure, diet, in-utero

Identifiers

Local EPrints ID: 70305
URI: https://eprints.soton.ac.uk/id/eprint/70305
PURE UUID: 8087e8a2-21d3-4ad3-9526-eccda5a1406f
ORCID for F. Cagampang: ORCID iD orcid.org/0000-0003-4404-9853
ORCID for M. Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for C. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

Catalogue record

Date deposited: 03 Feb 2010
Last modified: 11 Dec 2018 01:34

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