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Animal Models

Leptin intake in suckling rats restores altered T3 levels and markers of adipose tissue sympathetic drive and function caused by gestational calorie restriction

International Journal of Obesity volume 39, pages 959–966 (2015)Cite this article

Subjects

Abstract

Background:

Maternal calorie restriction during gestation in rats has been associated with altered white adipose tissue (WAT) sympathetic innervation and function in offspring. Here, we aimed to investigate whether supplementation with oral leptin (a breast milk component) throughout the lactation period may revert the aforementioned adverse programming effects.

Methods:

Three groups of male and female rats were studied at the postnatal day 25: the offspring of control dams, the offspring of 20% calorie-restricted dams during pregnancy (CR) and CR rats supplemented with physiological doses of leptin throughout lactation (CR-Leptin). Tyrosine hydroxylase (TH) levels and its immunoreactive area, and mRNA expression levels of lipid metabolism-related genes and of deiodinase iodothyronine type II (Dio2) were determined in WAT. Triiodothyronine (T3) levels were determined in the blood.

Results:

In CR males, leptin treatment restored the decreased TH levels and its immunoreactive area in WAT, and partially normalized expression levels of genes related to lipolysis and fatty acid oxidation (adipose triglyceride lipase, hormone-sensitive lipase, carnitine palmitoyltransferase 1b and peroxisome proliferator-activated receptor gamma coactivator 1-alpha). Leptin treatment also reverted the decreased T3 plasma levels and WAT lipoprotein lipase mRNA levels occurring in CR males and females, and the decreased Dio2 mRNA levels in CR females.

Conclusions:

Leptin supplementation throughout the lactation period reverts the malprogrammed effects on WAT structure and function induced by undernutrition during pregnancy. These findings support the relevance of the intake of leptin during lactation, bearing clear characteristics of essential nutrient, and provide a strategy to treat and/or prevent the programmed trend to obesity acquired by inadequate fetal nutrition.

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Acknowledgements

The research leading to these results was supported by the Spanish Government (grant AGL2012-33692), a grant from Fundación Ramón Areces (XVI Concurso Nacional), the European Union’s Seventh Framework Programme FP72007-2013 under grant agreement 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 belongs to the Nutrigenomics-group, awarded as 'Group of Excellence' of CAIB and supported by 'Direcció General d’Universitats, Recerca I Transferència del Coneixement' of Regional Government (CAIB) and FEDER funds (EU Contract: n. FP6-506360). JK is granted with a PhD fellowship entitled 'beca para la formación de personal investigador, en el marco de un programa operativo cofinanciado por el Fondo Social Europeo'. We thank Enzo Ceresi for technical assistance in immunohistochemical analysis.

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Authors and Affiliations

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

    J Konieczna, M Palou, J Sánchez, C Picó & A Palou

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  1. J Konieczna
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Correspondence to C Picó.

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Competing interests

AP, CP and JS 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). AP, CP, JK, JS and MP are authors of a patent application of the University of the Balearic Islands entitled 'Method for the prediction and or prevention of overweight, obesity and/or its complications by gene expression analyses'. (P201430428, Spain) (Priority data: 26 March 2014).

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Konieczna, J., Palou, M., Sánchez, J. et al. Leptin intake in suckling rats restores altered T3 levels and markers of adipose tissue sympathetic drive and function caused by gestational calorie restriction. Int J Obes 39, 959–966 (2015). https://doi.org/10.1038/ijo.2015.22

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