Journal article

Publication year: 2009

Pages: 241-250

Journal: Journal of Molecular Endocrinology

Volume number: 43

Issue number: 6

ISSN: 0952-5041

DOI Link: https://doi.org/10.1677/JME-09-0064

Publisher: BioScientifica

Abstract: 
Previous studies have shown that genes involved in fatty acid uptake, fatty acid oxidation, and thermogenesis are downregulated in liver and skeletal muscle of rats during lactation. However, biochemical mechanisms underlying these important metabolic adaptations during lactation have not yet been elucidated. As all these genes are transcriptionally regulated by peroxisome proliferator-activated receptor alpha (Ppar alpha), we hypothesized that their downregulation is mediated by a suppression of Ppar alpha during lactation. In order to investigate this hypothesis, we performed an experiment with lactating and nonlactating Ppar alpha knockout and corresponding wild-type mice. In wild-type mice, lactation led to a considerable downregulation of Ppar alpha, Ppar coactivators Pgc1 alpha and Pgc1 beta, and Ppar alpha target genes involved in fatty acid uptake, fatty acid oxidation, and thermogenesis in liver and skeletal muscle (P < 0.05). Ppar alpha knockout mice had generally a lower expression of all these Ppar alpha target genes in liver and skeletal muscle. However, in those mice, lactation did not lower the expression of genes involved in fatty acid utilization and thermogenesis in liver and skeletal muscle. Expression levels of Ppar alpha target genes in lactating wild-type mice were similar than in lactating or nonlactating Ppar alpha knockout mice. In conclusion, the present findings suggest that downregulation of Ppar alpha and its coactivators in tissues with high rates of fatty acid catabolism is responsible for the reduced utilization of fatty acids in liver and skeletal muscle and the reduced thermogenesis occurring in the lactating animal, which aim to conserve energy and metabolic substrates for milk production in the mammary gland.

Harvard Citation style: Gutgesell, A., Ringseis, R., Schmidt, E., Brandsch, C., Stangl, G. and Eder, K. (2009) Downregulation of peroxisome proliferator-activated receptor alpha and its coactivators in liver and skeletal muscle mediates the metabolic adaptations during lactation in mice, Journal of Molecular Endocrinology, 43(6), pp. 241-250. https://doi.org/10.1677/JME-09-0064

APA Citation style: Gutgesell, A., Ringseis, R., Schmidt, E., Brandsch, C., Stangl, G., & Eder, K. (2009). Downregulation of peroxisome proliferator-activated receptor alpha and its coactivators in liver and skeletal muscle mediates the metabolic adaptations during lactation in mice. Journal of Molecular Endocrinology. 43(6), 241-250. https://doi.org/10.1677/JME-09-0064