Postnatal induction of muscle fatty acid oxidation in mice differing in propensity to obesity: a role of pyruvate dehydrogenase

0524161 - FGÚ 2021 RIV GB eng J - Článek v odborném periodiku
Burešová, Jana - Janovská, Petra - Kuda, Ondřej - Křížová, J. - Romijnders-van der Stelt, I. - Keijer, J. - Hansíková, H. - Rossmeisl, Martin - Kopecký, Jan
Postnatal induction of muscle fatty acid oxidation in mice differing in propensity to obesity: a role of pyruvate dehydrogenase.
International Journal of Obesity. Roč. 44, č. 1 (2020), s. 235-244. ISSN 0307-0565. E-ISSN 1476-5497
Grant CEP: GA ČR(CZ) GB14-36804G
Institucionální podpora: RVO:67985823
Klíčová slova: postnatal development * leptin * AMP-activated protein kinase * A/J mice * C57BL/6J mice
Obor OECD: Endocrinology and metabolism (including diabetes, hormones)
Impakt faktor: 5.095, rok: 2020
Způsob publikování: Omezený přístup
https://doi.org/10.1038/s41366-018-0281-0

Adaptation to the extrauterine environment depends on a switch from glycolysis to catabolism of fatty acids (FA) provided as milk lipids. We sought to learn whether the postnatal induction of muscle FA oxidation in mice could reflect propensity to obesity and to characterize the mechanisms controlling this induction. Experiments were conducted using obesity-resistant A/J and obesity-prone C57BL/6J (B6) mice maintained at 30 °C, from 5 to 28 days after birth. At day 10, both A/J and B6 mice with genetic ablation (KO) of α2 subunit of AMP-activated protein kinase (AMPK) were also used. In skeletal muscle, expression of selected genes was determined using quantitative real-time PCR, and AMPK subunits content was evaluated using Western blotting. Activities of both AMPK and pyruvate dehydrogenase (PDH), as well as acylcarnitine levels in the muscle were measured. Acylcarnitine levels and gene expression indicated transient increase in FA oxidation during the first 2 weeks after birth, with a stronger increase in A/J mice. These data correlated with (i) the surge in plasma leptin levels, which peaked at day 10 and was higher in A/J mice, and (ii) relatively low activity of PDH linked with up-regulation of PDH kinase 4 gene (Pdk4) expression in the 10-day-old A/J mice. In contrast with the Pdk4 expression, transient up-regulation of uncoupling protein 3 gene was observed in B6 but not A/J mice. AMPK activity changed during the development, without major differences between A/J and B6 mice. Expression of neither Pdk4 nor other muscle genes was affected by AMPK-KO. Our results indicate a relatively strong postnatal induction of FA oxidation in skeletal muscle of the obesity-resistant A/J mice. This induction is transient and probably results from suppression of PDH activity, linked with a postnatal surge in plasma leptin levels, independent of AMPK.
Trvalý link: http://hdl.handle.net/11104/0308524