McCurdy 2016 JCI Insight

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McCurdy CE, Schenk S, Hetrick B, Houck J, Drew BG, Kaye S, Lashbrook M, Bergman BC, Takahashi DL, Dean TA, Nemkov T, Gertsman I, Hansen KC, Philp A, Hevener AL, Chicco AJ, Aagaard KM, Grove KL, Friedman JE (2016) Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques. JCI Insight 1:e86612.

» PMID: 27734025 Open Access

McCurdy CE, Schenk S, Hetrick B, Houck J, Drew BG, Kaye S, Lashbrook M, Bergman BC, Takahashi DL, Dean TA, Nemkov T, Gertsman I, Hansen KC, Philp A, Hevener AL, Chicco AJ, Aagaard KM, Grove KL, Friedman JE (2016) JCI Insight

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.


O2k-Network Lab: US CA San Diego Schenk S, US CO Aurora Jackman MR, US CO Fort Collins Chicco AJ


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Inherited, Obesity, Other 

Organism: Other mammals  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS  HRR: Oxygraph-2k 

2016-12 

NOTE: Muscle fibres were preserved in ice-cold BIOPS overnight before measurements.