Abstract
A maternal high-fat (HF) diet during pregnancy can lead to metabolic compromise, such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (mtTFA) were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS) respiratory complex subunits were suppressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%), which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%). Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle.
Highlights
Significant increases in type 2 diabetes (T2D) and obesity rates that have been observed worldwide over the past three decades are the combined result of high energy intake, a sedentary lifestyle and genetic predisposition (Hill and Peters, 1998)
High maternal fat intake leads to insulin resistance in offspring (Armitage et al, 2005) which is associated with decreases in mitochondrial function and content including; liver mitochondrial DNA (mtDNA) copy number (Taylor et al, 2005; Burgueño et al, 2013) aortic smooth muscle mitochondrial gene expression (Taylor et al, 2005), and activity of the electron transport system (ETS) enzyme complex in liver (Bruce et al, 2009a)
Skeletal muscle Irs1 and Glut4 mRNA expression was decreased in hf offspring (p < 0.05; Table 1)
Summary
Significant increases in type 2 diabetes (T2D) and obesity rates that have been observed worldwide over the past three decades are the combined result of high energy intake, a sedentary lifestyle and genetic predisposition (Hill and Peters, 1998). High maternal fat intake leads to insulin resistance in offspring (Armitage et al, 2005) which is associated with decreases in mitochondrial function and content including; liver mtDNA copy number (Taylor et al, 2005; Burgueño et al, 2013) aortic smooth muscle mitochondrial gene expression (Taylor et al, 2005), and activity of the ETS enzyme complex in liver (Bruce et al, 2009a). A maternal diet high in fat and sucrose resulted in the significant alteration of gene expression in the skeletal muscle transcriptome, including downregulation of genes associated with mitochondrial oxidative function (Latouche et al, 2014). To date, studies examining the effects of maternal diet on offspring skeletal muscle mitochondrial function have used mixed obesogenic maternal diets (Shelley et al, 2009; Latouche et al, 2014), leaving the effects
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