Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring.

Latouche,C, Heywood,SE, Henry,SL, Ziemann,M, Lazarus,R, El-Osta,A, Armitage,JA and Kingwell,BA 2014, Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring., The Journal of Nutrition, vol. 144, no. 3, pp. 237-244, doi: 10.3945/jn.113.186775.

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Title Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring.
Author(s) Latouche,C
Heywood,SE
Henry,SL
Ziemann,M
Lazarus,R
El-Osta,A
Armitage,JAORCID iD for Armitage,JA orcid.org/0000-0002-3762-0911
Kingwell,BA
Journal name The Journal of Nutrition
Volume number 144
Issue number 3
Start page 237
End page 244
Total pages 8
Publisher American Society for Nutrition
Place of publication Bethesda, Md, United States
Publication date 2014-03-01
ISSN 1541-6100
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Nutrition & Dietetics
HIGH-FAT DIET
METABOLIC SYNDROME
MITOCHONDRIAL DYSFUNCTION
DEVELOPMENTAL ORIGINS
EXPERIMENTAL-MODELS
POSTWEANING DIET
INDUCED OBESITY
PROTEIN-DIET
RICH DIET
Animal Nutritional Physiological Phenomena
Animals
Computational Biology
DNA Copy Number Variations
Diet, High-Fat
Female
Gene Expression Profiling
Insulin
Insulin Resistance
Lactation
Male
Maternal Nutritional Physiological Phenomena
Mitochondrial Proteins
Muscle, Skeletal
Overnutrition
Oxidative Phosphorylation
Phenotype
Pregnancy
Summary Children of obese mothers have increased risk of metabolic syndrome as adults. Here we report the effects of a high-fat diet in the absence of maternal obesity at conception on skeletal muscle metabolic and transcriptional profiles of adult male offspring. Female Sprague Dawley rats were fed a diet rich in saturated fat and sucrose [high-fat diet (HFD): 23.5% total fat, 9.83% saturated fat, 20% sucrose wt:wt] or a normal control diet [(CD) 7% total fat, 0.5% saturated fat, 10% sucrose wt:wt] for the 3 wk prior to mating and throughout pregnancy and lactation. Maternal weights were not different at conception; however, HFD-fed dams were 22% heavier than controls during pregnancy. On a normal diet, the male offspring of HFD-fed dams were not heavier than controls but demonstrated features of insulin resistance, including elevated plasma insulin concentration [40.1 ± 2.5 (CD) vs 56.2 ± 6.1 (HFD) mU/L; P = 0.023]. Next-generation mRNA sequencing was used to identify differentially expressed genes in the offspring soleus muscle, and gene set enrichment analysis (GSEA) was used to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 upregulated pathways, including cytokine signaling (P < 0.005), starch and sucrose metabolism (P < 0.017), inflammatory response (P < 0.024), and cytokine-cytokine receptor interaction (P < 0.037). A further 8 pathways were downregulated, including oxidative phosphorylation (P < 0.004), mitochondrial matrix (P < 0.006), and electron transport/uncoupling (P < 0.022). Phosphorylation of the insulin signaling protein kinase B was reduced [2.86 ± 0.63 (CD) vs 1.02 ± 0.27 (HFD); P = 0.027] and mitochondrial complexes I, II, and V protein were downregulated by 50-68% (P < 0.005). On a normal diet, the male offspring of HFD-fed dams did not become obese adults but developed insulin resistance, with transcriptional evidence of muscle cytokine activation, inflammation, and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of prepregnancy obesity, can promote metabolic dysregulation and predispose offspring to type 2 diabetes.
Language eng
DOI 10.3945/jn.113.186775
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, American Society for Nutrition
Persistent URL http://hdl.handle.net/10536/DRO/DU:30070177

Document type: Journal Article
Collection: School of Medicine
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