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Litter size variation in hypothalamic gene expression determines adult metabolic phenotype in Brandt's voles (Lasiopodomys brandtii).

Zhang XY, Zhang Q, Wang DH - PLoS ONE (2011)

Bottom Line: 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.As a result, the agouti-related peptide (AgRP) mRNA increased in the offspring from small litters.Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

ABSTRACT

Background: Early 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 findings: Hypothalamic 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/significance: These 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.

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Serum leptin (A, weaning; B, adult), T3 (tri-iodothyronine, E) and T4 (thyroxine, F) levels in male and female voles from large and small litters.The adult serum leptin was correlated positively with body mass (C), but not with food intake (D). Values are presented as mean±SE. Group differences are expressed as P<0.05, and bars with different letters differed significantly from each other.
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pone-0019913-g002: Serum leptin (A, weaning; B, adult), T3 (tri-iodothyronine, E) and T4 (thyroxine, F) levels in male and female voles from large and small litters.The adult serum leptin was correlated positively with body mass (C), but not with food intake (D). Values are presented as mean±SE. Group differences are expressed as P<0.05, and bars with different letters differed significantly from each other.

Mentions: At weaning, there was no difference in serum leptin between litters (F1, 39 = 2.448, P>0.05) or gender (F1, 39 = 0.001, P>0.05) (Fig. 2A). Adult female voles had higher serum leptin levels compared to males (ANCOVA, F1, 39 = 5.340, P<0.05; Fig. 2B), but serum leptin in adulthood was not influenced by litter size (ANCOVA, F1, 39 = 0.171, P>0.05) (Fig. 2B). In adulthood, serum leptin was correlated positively with body mass (r = 0.340, P<0.05; Fig. 2C), but not with food intake (r = 0.146, P>0.05; Fig. 2D).


Litter size variation in hypothalamic gene expression determines adult metabolic phenotype in Brandt's voles (Lasiopodomys brandtii).

Zhang XY, Zhang Q, Wang DH - PLoS ONE (2011)

Serum leptin (A, weaning; B, adult), T3 (tri-iodothyronine, E) and T4 (thyroxine, F) levels in male and female voles from large and small litters.The adult serum leptin was correlated positively with body mass (C), but not with food intake (D). Values are presented as mean±SE. Group differences are expressed as P<0.05, and bars with different letters differed significantly from each other.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3102676&req=5

pone-0019913-g002: Serum leptin (A, weaning; B, adult), T3 (tri-iodothyronine, E) and T4 (thyroxine, F) levels in male and female voles from large and small litters.The adult serum leptin was correlated positively with body mass (C), but not with food intake (D). Values are presented as mean±SE. Group differences are expressed as P<0.05, and bars with different letters differed significantly from each other.
Mentions: At weaning, there was no difference in serum leptin between litters (F1, 39 = 2.448, P>0.05) or gender (F1, 39 = 0.001, P>0.05) (Fig. 2A). Adult female voles had higher serum leptin levels compared to males (ANCOVA, F1, 39 = 5.340, P<0.05; Fig. 2B), but serum leptin in adulthood was not influenced by litter size (ANCOVA, F1, 39 = 0.171, P>0.05) (Fig. 2B). In adulthood, serum leptin was correlated positively with body mass (r = 0.340, P<0.05; Fig. 2C), but not with food intake (r = 0.146, P>0.05; Fig. 2D).

Bottom Line: 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.As a result, the agouti-related peptide (AgRP) mRNA increased in the offspring from small litters.Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

ABSTRACT

Background: Early 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 findings: Hypothalamic 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/significance: These 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.

Show MeSH
Related in: MedlinePlus