Maternal low protein diet induces muscle mitochondrial respiration impairment, catch‐up growth and PGC‐1α expression (271.6)

Abstract

Malnutrition during the fetal growth period followed by postnatal catch‐up growth results in obesity and the development of type 2 diabetes (T2D). To determine whether a prenatal low protein diet followed by postnatal high fat diet increase offspring’s propensity to obesity and T2D, obese‐prone female Sprague‐Dawley rats were fed 8% (low protein; LP) or 20% protein (normal protein; NP) diets 3 weeks prior to mating. Dams were fed the same diet during pregnancy and lactation. Postnatally, male offspring were fed 10% (normal fat; NF) or 45% (high fat; HF) diets for 12 weeks. Maternal LP and post natal HF diets resulted in offspring obesity and increased insulin resistance. Recent studies showed that reduction in peroxisome proliferator‐activated receptor‐gamma coactivator‐1alpha (PGC‐1α) increases risk for T2D due to decreased mitochondria biogenesis and oxidative metabolic function. No studies have demonstrated whether maternal LP and postnatal HF diets influence muscle PGC‐1α expression, mitochondria biogenesis, and mitochondrial oxidative respiratory functions. Data showed that skeletal muscle PGC‐1α protein expression is increased while mitochondrial oxygen consumption rate is decreased by maternal LP while postnatal HF diets had no effect. Mitochondria biogenesis, mRNA expression of mitochondrial biogenic factors including nuclear respiratory factor 1 (NRF1) and cytochrome c oxidase 1and 4 (COX‐1 and 4) were unaffected by maternal LP and postnatal HF diets. Interestingly, skeletal muscle mitochondrial expression of acetylated succinate dehydrogenase was increased which may account for the decreased skeletal muscle mitochondrial respiratory in LP offspring. Taken together these data suggest that maternal LP and postnatal HF diets increase risk for T2D and muscle catch‐up growth while decreasing oxidative metabolic function.Grant Funding Source: Supported by USDA Agricultural Research Service Project #5450‐51000‐047‐00D.