Maternal Environmental Contribution to Adult Sensitivity and Resistance to Obesity in Long Evans Rats

The OLETF rat is an animal model of early onset hyperphagia induced obesity, presenting multiple pre-obese characteristics during the suckling period. In the present study, we used a cross-fostering strategy to assess whether interactions with obese dams in the postnatal environment contributed to the development of obesity.On postnatal Day (PND)-1 OLETF and control LETO pups were cross-fostered to same or opposite strain dams. An independent ingestion test was performed on PND11 and a nursing test on PND18. Rats were sacrificed at weaning or on PND90, and plasma leptin, insulin, cholesterol, triglycerides and alanine aminotransferase (ALT) were assayed. Fat pads were collected and weighed and adipocyte size and number were estimated. Body weight and intake, as well as the estrous cycle of the female offspring were monitored.During the suckling period, the pups' phenotype was almost completely determined by the strain of the mother. However, pups independently ingested food according to their genotype, regardless of their actual phenotype. At adulthood, cross fostered males of both strains and LETO females were affected in regard of their adiposity levels in the direction of the foster dam. On the other hand, OLETF females showed almost no alterations in adiposity but were affected by the strain of the dams in parameters related to the metabolic syndrome. Thus, OLETF females showed reduced liver adiposity and circulating levels of ALT, while LETO females presented a disrupted estrous cycle and increased cholesterol and triglycerides in the long term.The present study provides further support for the early postnatal environment playing a sex-divergent role in programming later life phenotype. In addition, it plays a more central role in determining the functioning of mechanisms involved in energy balance that may provide protection from or sensitivity to later life obesity and pathologies related to the metabolic syndrome

Estimation of the adipocyte number (expressed as percent of BW).

<p><b>A</b>: LdLp pups vs. OdLp pups at weaning; <b>B</b>: OdOp pups vs. LdOp pups at weaning; <b>C</b>: LdLp pups vs. OdLp pups on PND90; <b>D</b>: OdOp pups vs. LdOp pups on PND90. Data are presented in means and SEM. *p<0.05 for pup-strain comparison between same-sex cross and in-fostering groups. N = 4–6 per group.</p

Estimation of the adipocyte number (expressed as percent of BW).

<p><b>A</b>: LdLp pups vs. OdLp pups at weaning; <b>B</b>: OdOp pups vs. LdOp pups at weaning; <b>C</b>: LdLp pups vs. OdLp pups on PND90; <b>D</b>: OdOp pups vs. LdOp pups on PND90. Data are presented in means and SEM. *p<0.05 for pup-strain comparison between same-sex cross and in-fostering groups. N = 4–6 per group.</p

Estrous cycle parameters.

<p><b>A</b>: Females' estrous cycle structure. Data are presented in percentages of total cycles examined. **p<0.01, ***p<0.001 for pup-strain comparison between cross and in-fostering groups. 4D: 4 day cycles, 5DD: 5day double estrous cycle and 5EE: 5 day double estrous cycles. <b>B</b>: Intake (kcal) across the cycle in the LETO strain and <b>C</b>: Intake (kcal) across the cycle in the OLETF strain. Data are presented mean and SEM.</p

Total white fat (expressed as percent of BW).

<p><b>A</b>: LdLp pups vs. OdLp pups at weaning; <b>B</b>: OdOp pups vs. LdOp pups at weaning; <b>C</b>: LdLp pups vs. OdLp pups on PND90; <b>D</b>: OdOp pups vs. LdOp pups on PND90. Data are presented in means and SEM. *p<0.05 for pup-strain comparison between same-sex cross and in-fostering groups. N = 6–7 per group.</p

Plasma leptin levels.

<p><b>A</b>: LdLp pups vs. OdLp pups at weaning; <b>B</b>: OdOp pups vs. LdOp pups at weaning; <b>C</b>: LdLp pups vs. OdLp pups on PND90; <b>D</b>: OdOp pups vs. LdOp pups on PND90. Data are presented in means and SEM. *p<0.05 for pup-strain comparison between same-sex cross and in-fostering groups. N = 5–6 per group.</p

Weight of the different fat pads in the LETO strain.

<p>Data are presented in mean and SEM.</p><p>*p<0.05, for significant group differences within each strain and sex (in grams);</p><p>#p<0.05, for significant group differences within each strain and sex (in percentages).</p

Experimental Design.

<p>Experimental Design.</p