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Animal Models

Oral leptin supplementation throughout lactation in rats prevents later metabolic alterations caused by gestational calorie restriction

International Journal of Obesity volume 41, pages 360–371 (2017)Cite this article

Subjects

Abstract

Objectives:

Calorie-restriction during gestation in rats has been seen to produce lasting detrimental effects in the offspring, affecting energy balance control and other related metabolic functions. Our aim was to assess whether leptin supplementation throughout lactation may prevent the dysmetabolic phenotype in adulthood associated with gestational calorie restriction.

Methods:

Three groups of male Wistar rats were followed: the offspring of ad libitum fed dams (controls); the offspring of 20% calorie-restricted dams during gestation (CR); and CR rats supplemented with physiological doses of leptin throughout lactation (CR-Leptin). Pups were weaned with a standard diet (SD) until 4 months of age, and then half of the animals of each group were moved to a Western diet (WD) until 6 months of age. Body weight and food intake were recorded. Energy expenditure, locomotive activity, blood parameters, liver triglycerides (TG), and gene expression and specific proteins in liver and white adipose tissue (WAT) were measured in adulthood.

Results:

Adult CR rats, but not CR-Leptin rats, displayed greater adiposity index and feed efficiency (both under SD) than controls, along with lower locomotive activity and energy expenditure, higher HOMA-IR index and greater circulating TG and leptin levels. CR animals also exhibited increased values of the respiratory exchange ratio and more severe signs of hepatic steatosis under WD than CR-Leptin animals. Gene expression analysis revealed that CR, but not CR-Leptin, animals displayed indicators of lower capacity for WAT expansion, along with decreased lipogenesis and lipolytic capacity under SD, and impaired lipogenic response of the liver to WD feeding, in accordance with diminished insulin sensitivity and WAT leptin signaling.

Conclusions:

Oral leptin supplementation in physiological doses throughout lactation in rats prevents most of the detrimental effects on energy homeostasis and metabolic alterations in adulthood caused by inadequate fetal nutrition.

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Acknowledgements

We thank Enzo Ceresi and Paula Núñez for technical assistance in immunohistochemistry analysis and Western blot analysis, respectively. The research leading to these results was supported by the Spanish Government (grants AGL2012-33692 and AGL2015-67019-P), the European Union’s Seventh Framework Programme FP7 2007-2013 under grant agreements n. 244995 (BIOCLAIMS Project), and the Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, CIBERobn. The Laboratory of Molecular Biology, Nutrition, and Biotechnology (Nutrigenomics) is a member of the European Research Network of Excellence NuGO (The European Nutrigenomics Organization, EU Contract: n. FP6-506360). Nara Szostaczuk has been granted a PhD fellowship entitled ‘beca para la formación de personal investigador’, co-funded by the Regional Government (Conselleria d'Educació, Cultura i Universitats, CAIB) and the European Social Fund (FSE).

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Authors and Affiliations

  1. Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Balearic Islands, Spain

    N Szostaczuk, T Priego, M Palou, A Palou & C Picó

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  1. N Szostaczuk
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Correspondence to A Palou.

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Competing interests

AP and CP are authors of a patent held by the University of the Balearic Islands entitled ‘Use of leptin for the prevention of excess body weight and composition containing leptin’ (WO 2006089987 A1; Priority data: 23 February 2005).

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Szostaczuk, N., Priego, T., Palou, M. et al. Oral leptin supplementation throughout lactation in rats prevents later metabolic alterations caused by gestational calorie restriction. Int J Obes 41, 360–371 (2017). https://doi.org/10.1038/ijo.2016.241

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