Journal article
PPAR signaling pathway is a key modulator of liver proteome in pups born to vitamin B-12 deficient rats
Journal of proteomics, Vol.91, pp.297-308
10/08/2013
DOI: 10.1016/j.jprot.2013.07.027
PMID: 23928364
Abstract
Maternal nutritional deficiency in-utero is known to predict risk of complex disorders like cardiovascular disease, diabetes and many neurological disorders in the offspring and vitamin B-12 is one such critical micronutrient. Here we performed 2D-DIGE followed by MALDI TOF/TOF analysis to identify proteins that are differentially expressed in liver of pups born to mothers fed vitamin B-12 deficient diet vis-a-vis control diet. To further establish causality, we analyzed the effect of B-12 rehabilitation at parturition on the protein levels and the phenotype in pups. We identified 38 differentially expressed proteins that were enriched in pathways involved in the regulation of amino acid, lipid and carbohydrate metabolism. Further, three enzymes in the beta-oxidation pathway (hydroxyacyl-coenzyme A dehydrogenase, medium-chain specific acyl-CoA dehydrogenase, 3-ketoacyl-CoA thiolase) were down-regulated in pups born to mothers fed vitamin B-12 deficient diet. We observed age-dependent differential expression of peroxisome proliferator activated-receptor (PPAR) alpha and gamma in the deficient pups. Interestingly, expression of 27 proteins that were differentially expressed was restored to the control levels after rehabilitation of female rats with vitamin B-12 from parturition. Our study thus provides the first evidence that maternal vitamin B-12 deficiency influences lipid and other micronutrient metabolism in pups through regulation of PPAR signaling pathway.
Biological significance
Maternal vitamin B-12 deficiency has been shown to predict the onset of complex disorders like atherosclerosis, type II diabetes etc. in the next generation during their adulthood. We have shown earlier that pups born to female rats fed with vitamin B-12 deficient diet were obese and developed high levels of other intermediate traits such as triglycerides, cholesterol etc. that are related to the risk of diabetes and cardiovascular disorders. In this piece of work using differential proteomic approach we have identified the altered metabolic processes in the liver of vitamin B-12 deficient pups. We have also documented that the proteins involved in beta-oxidation pathway are down-regulated. Further, differential expression of PPAR alpha and PPAR gamma was evidently documented as the master regulator for the alteration of lipid, amino acid and carbohydrate metabolism during maternal vitamin B-12 deficiency. (C) 2013 Elsevier B.V. All rights reserved.
Details
- Title: Subtitle
- PPAR signaling pathway is a key modulator of liver proteome in pups born to vitamin B-12 deficient rats
- Creators
- Shadab Ahmad - Institute of Genomics and Integrative BiologyK. Anand Kumar - National Institute of NutritionTrayambak Basak - Institute of Genomics and Integrative BiologyGourav Bhardwaj - Institute of Genomics and Integrative BiologyDilip K. Yadav - Centre for Cellular and Molecular BiologyA. Lalitha - National Institute of NutritionGiriraj Ratan Chandak - Centre for Cellular and Molecular BiologyManchala Raghunath - Centre for Cellular and Molecular BiologyShantanu Sengupta - Institute of Genomics and Integrative Biology
- Resource Type
- Journal article
- Publication Details
- Journal of proteomics, Vol.91, pp.297-308
- Publisher
- Elsevier
- DOI
- 10.1016/j.jprot.2013.07.027
- PMID
- 23928364
- ISSN
- 1874-3919
- eISSN
- 1876-7737
- Number of pages
- 12
- Grant note
- BSC 0118 / Council of Scientific and Industrial Research (CSIR) under the XII FYP
- Language
- English
- Date published
- 10/08/2013
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984359871502771
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