Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)

Abstract

BackgroundEarly postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10–12) and small (3–4) litter sizes, of Brandt's voles (Lasiopodomys brandtii), a rodent species from Inner Mongolia grassland in China.Methodology/Principal FindingsHypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb) mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3) mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP) mRNA increased in the offspring from small litters.Conclusions/SignificanceThese findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.

Sexual maturation in hens is not associated with increases in serum leptin and the expression of leptin receptor mRNA in hypothalamus

“…With a good agreement with our results, Bronson reported that there is no support for the hypothesis that an increase in body fat and thus an increase in circulating leptin trigger puberty in female mice [14]. Also, thyroid hormones are essential for photoinduced egg production [15] as well as being important for growth and development in vertebrates [16]. In the present study, photo-induced earlier egg production in hens was not accompanied the changes of thyroxine (T 4 ).…”

Maternal dietary protein supplement confers long-term sex-specific beneficial consequences of obesity resistance and glucose tolerance to the offspring in Brandt's voles

“…The previous studies showed that maternal energy or nutritional changes would influence energetic strategies and reproductive fitness (Lou et al, 2013;Watkins and Sinclair, 2014;Zhang et al, 2011aZhang et al, , 2011b. Maternal high-protein diet resulted in a small increase in digestible energy intake at peak lactation in Brandt's voles (Lou et al, 2013).…”

Calcium reduces vitamin D and glucocorticoid receptors in the visceral fat of obese male rats

“…In addition, the hyperphagia of SL rats can be explained by both the leptin resistance (Rodrigues et al 2009, Zhang et al 2011) and the higher NPY in the ARC. Previously, Plagemann and coworkers (1999) have shown that SL rats have higher NPY-immunopositive neurons at weaning, explaining their higher food intake since weaning.…”