Conner 2015 FASEB J

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Conner B, Hetrik B, Chicco A, McCurdy C (2015) Maternal obesity alters offspring muscle mitochondrial function in nonhuman primates. FASEB J 29:1036.7.

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Conner B, Hetrik B, Chicco A, McCurdy C (2015) FASEB J

Abstract: Offspring of obese mothers have increased risk for early obesity and insulin resistance. Impairment in mitochondrial (MT) function may be a primary mechanism leading to insulin resistance. This study seeks to determine if maternal western-style diet (WSD) or obesity alone alter fetal muscle MT function and if this persists at 3yrs. Adult Japanese Macaques were chronically (>2yr) fed a control (CON) or WSD. Some WSD-induced obese dams were switched to CON at the start of pregnancy (REV). Fetal samples were collected at gestational day 130/165. Offspring carried to term were weaned to a CON or WSD after exposure to either gestational WSD (WSD/WSD;WSD/CON) or CON (CON/WSD;CON/CON). Fetal and juvenile gastrocnemius fibers were assayed for MT function in the presence of carbohydrate (CHO) or palmitate (PALM) using high-resolution respirometry. Fetal respiratory control ratios (RCR) decreased in WSD and REV, demonstrating 24% increased uncoupling. CHO-stimulated state 3 respiration was reduced by 20% (p<0.01) in WSD and REV, but neither were significantly decreased in PALM. In juveniles, RCR was doubled in CON/WSD vs. CON/CON, but this increase did not occur in WSD/WSD. Likewise, CHO coupling control ratio was doubled in CON/CON vs. CON/WSD (p<0.05), but not in WSD/WSD. Maternal obesity with or without WSD reduces MT function and metabolic flexibility in fetal muscle. Inflexibility persists in the postnatal period, but only when lean offspring are challenged with WSD. Our data suggest that exposure to maternal obesity alters cellular systems responsible for MT adaptation to WSD and may contribute to increased risk of metabolic disease. Funding: NIH DK090964


O2k-Network Lab: US CO Fort Collins Chicco AJ


Labels: MiParea: Respiration, Developmental biology, Exercise physiology;nutrition;life style  Pathology: Obesity 

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


Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k