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Childhood obesity and insulin resistance in a Yucatan mini-piglet model: putative roles of IGF-1 and muscle PPARs in adipose tissue activity and development

Abstract

OBJECTIVE:

To explore metabolic and cellular modifications induced during childhood obesity, in a novel animal model of obese mini-piglets.

DESIGN:

A total of 10 four-month old Yucatan mini-pigs were followed from prepuberty to adulthood. Animals were divided into two groups. The first one had been overfed (OF) a western-type diet and the second one had been normally fed a control recommended human-type diet (NF).

MEASUREMENTS:

Plasma insulin-like growth factor 1 (IGF-1), insulin, leptin, nonesterified fatty acids, triglycerides (TGs) and glucose were determined at sexual maturity and at young adulthood. Quantitative gene expressions of peroxysome-proliferator-activated receptors (PPARs), glucose transporter 4, insulin receptor, IGF-1, leptin and interleukin-6 (IL-6) in skeletal muscle, adipose tissue and liver were also measured at both stages. Adult insulin sensitivity was measured via euglycaemic–hyperinsulinaemic clamps.

RESULTS:

Increased body weight in adult OF pigs was associated with increased body size and low insulin sensitivity. Sexually mature OF pigs had higher IGF-1 plasma concentrations than their lean littermates (P<0.05). In the OF group, TGs and glucose were both decreased (P<0.05). Muscle PPARγ and α in OF pubescent pigs as compared to NF pigs were 11 times higher and 20 times lower, respectively (P<0.01).

CONCLUSION:

Obesity and insulin resistance induced by overfeeding mini-pigs during development and puberty were not associated with the cluster of metabolic modifications frequently observed in their adult littermates. Increased IGF-1 concentrations and modifications of skeletal muscle PPAR (α and γ) expressions may help the young obese pig to partially regulate its glycaemia and triglyceridaemia through an increase of fat mass, which maintains its high insulin sensitivity.

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Acknowledgements

We express our gratitude to D Mésangeau and L Noah from Merck-Santé S.A. (Merck Santé, Centre de Recherche de Chilly-Mazarin, Chilly-Mazarin, France) for their financial and scientific contributions and Regions Payscle la Loire and Bretagne for their Financial support. We also thank C Bonnet for his technical assistance for mRNA extractions and gene expressions and G Poupeau and JL Lescure for taking care of mini-pigs.

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Correspondence to M M -J Champ.

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Sébert, S., Lecannu, G., Kozlowski, F. et al. Childhood obesity and insulin resistance in a Yucatan mini-piglet model: putative roles of IGF-1 and muscle PPARs in adipose tissue activity and development. Int J Obes 29, 324–333 (2005). https://doi.org/10.1038/sj.ijo.0802823

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