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Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques
Carrie E. McCurdy, … , Kevin L. Grove, Jacob E. Friedman
Carrie E. McCurdy, … , Kevin L. Grove, Jacob E. Friedman
Published October 6, 2016
Citation Information: JCI Insight. 2016;1(16):e86612. https://doi.org/10.1172/jci.insight.86612.
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Research Article Metabolism Muscle biology

Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques

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Abstract

Maternal obesity is proposed to alter the programming of metabolic systems in the offspring, increasing the risk for developing metabolic diseases; however, the cellular mechanisms remain poorly understood. Here, we used a nonhuman primate model to examine the impact of a maternal Western-style diet (WSD) alone, or in combination with obesity (Ob/WSD), on fetal skeletal muscle metabolism studied in the early third trimester. We find that fetal muscle responds to Ob/WSD by upregulating fatty acid metabolism, mitochondrial complex activity, and metabolic switches (CPT-1, PDK4) that promote lipid utilization over glucose oxidation. Ob/WSD fetuses also had reduced mitochondrial content, diminished oxidative capacity, and lower mitochondrial efficiency in muscle. The decrease in oxidative capacity and glucose metabolism was persistent in primary myotubes from Ob/WSD fetuses despite no additional lipid-induced stress. Switching obese mothers to a healthy diet prior to pregnancy did not improve fetal muscle mitochondrial function. Lastly, while maternal WSD alone led only to intermediary changes in fetal muscle metabolism, it was sufficient to increase oxidative damage and cellular stress. Our findings suggest that maternal obesity or WSD, alone or in combination, leads to programmed decreases in oxidative metabolism in offspring muscle. These alterations may have important implications for future health.

Authors

Carrie E. McCurdy, Simon Schenk, Byron Hetrick, Julie Houck, Brian G. Drew, Spencer Kaye, Melanie Lashbrook, Bryan C. Bergman, Diana L. Takahashi, Tyler A. Dean, Travis Nemkov, Ilya Gertsman, Kirk C. Hansen, Andrew Philp, Andrea L. Hevener, Adam J. Chicco, Kjersti M. Aagaard, Kevin L. Grove, Jacob E. Friedman

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Figure 3

Maternal obesity combined with a Western-style diet (WSD) increases fetal muscle electron transfer system (ETS) activity but not mitochondrial abundance.

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Maternal obesity combined with a Western-style diet (WSD) increases feta...
ETS enzymatic activities for mitochondrial (A) complex (C) I, (B) CII, (C) CI+III, and (D) CIV as well as (E) citrate synthase (CS) activity were measured by spectrophotometry in male (M; circles) and female (F; triangles) fetal gastrocnemius muscle from lean/overweight dams that had only received control diet (Ln/CTR; n = 10–11 M, 15–16 F), Ln/WSD (n = 6 M, 5–7 F), and obese dams chronically fed a WSD (Ob/WSD; n = 13 M, 12 F) groups. (F) An estimate of mitochondrial number was calculated as the ratio of expression for the mitochondrial gene, cytochrome B (CYTB), to the nuclear gene, hemoglobin beta (HBB), in fetal muscle from Ln/CTR (n = 9 M, 12 F), Ln/WSD (n = 8 M, 5 F) and Ob/WSD (n = 11 M, 6 F). Values are expressed relative to ribosomal protein S15 (RPS15). All data were analyzed by 2-way ANOVA (maternal group × fetal sex) with post-hoc tests. P values for significant main effects are listed in each graph. Letters are used to indicate significant post-hoc differences. Groups with the same letter are not significantly different from each other. Individual data points and the group mean ± SEM are shown.

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