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A maternal Western-style diet impairs skeletal muscle lipid metabolism in adolescent Japanese macaques

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posted on 2023-09-19, 22:19 authored by Keenan T. Greyslak, Byron Hetrick, Bryan C. Bergman, Tyler A. Dean, Stephanie R. Wesolowski, Maureen Gannon, Simon Schenk, Elinor L. Sullivan, Kjersti M. Aagaard, Paul Kievit, Adam J. Chicco, Jacob E. Friedman, Carrie E. McCurdy

Maternal (m) consumption of a Western-style diet (WD) during pregnancy alters fatty-acid metabolism and reduces insulin sensitivity in fetal skeletal muscle. The long-term impact of these fetal adaptations and the pathways underlying disordered lipid metabolism are incompletely understood. Therefore, we tested whether a mWD chronically fed to lean, insulin sensitive adult Japanese macaques throughout pregnancy and lactation would impact skeletal muscle oxidative capacity and lipid metabolism in adolescent offspring fed a postweaning (pw)WD or control diet (CD). Although body weight was not different, retroperitoneal fat mass and subscapular skinfold thickness were significantly higher in pwWD offspring consistent with elevated fasting insulin and glucose. Maximal complex I-dependent respiration in muscle was lower in mWD offspring in the presence of fatty acids, suggesting that mWD impacts muscle integration of lipid with non-lipid oxidation. Abundance of all five OXPHOS complexes and VDAC, but not ETF/ETFDH, were reduced with mWD, partially explaining the lower respiratory capacity with lipids. Muscle triglycerides increased with pwWD; however, the fold increase in lipid saturation, 1,2-diacylglycerides and C18: ceramide between pwCD and pwWD was greatest in mWD offspring. Reductions in complex I abundance and VDAC correlated with reduced markers of oxidative stress suggesting these reductions may be an early life adaptation to mWD to mitigate excess reactive oxygen species. Altogether, mWD, independent of maternal obesity or insulin resistance, results in sustained metabolic reprogramming in offspring muscle despite a healthy diet intervention.

Funding

Eugene and Clarissa Evonuk Memorial Graduate Fellowship

NIH P51 OD011092 R01 DK089201 R01 DK128187 R01 MH107508 R24 DK090964

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