The Downregulation of the Liver Lipid Metabolism Induced by Hypothyroidism in Male Mice: Metabolic Flexibility Favors Compensatory Mechanisms in White Adipose Tissue

被引:1
作者
Chamas, Lamis [1 ]
Seugnet, Isabelle [1 ]
Tanve, Odessa [1 ,3 ]
Enderlin, Valerie [2 ]
Clerget-Froidevaux, Marie-Stephanie [1 ]
机构
[1] Museum Natl Hist Nat, CNRS MNHN UMR 7221 Physiol Mol & Adaptat Phyma, Dept Life Adaptat, 57 Rue Cuvier CP 32, F-75231 Paris 05, France
[2] Univ Paris Saclay, Paris Saclay Inst Neurosci Neuro PSI, CNRS UMR 9197, F-91400 Saclay, France
[3] Cervo Brain Res Ctr, 2301 Ave Estimauville, Quebec City, PQ G1E 1T2, Canada
关键词
hypothyroidism; metabolic flexibility; lipogenesis; white adipose tissue; liver; PTU (propylthiouracil); OBESITY; RATS; FAT; DISEASE;
D O I
10.3390/ijms251910792
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In mammals, the maintenance of energy homeostasis relies on complex mechanisms requiring tight synchronization between peripheral organs and the brain. Thyroid hormones (THs), through their pleiotropic actions, play a central role in these regulations. Hypothyroidism, which is characterized by low circulating TH levels, slows down the metabolism, which leads to a reduction in energy expenditure as well as in lipid and glucose metabolism. The objective of this study was to evaluate whether the metabolic deregulations induced by hypothyroidism could be avoided through regulatory mechanisms involved in metabolic flexibility. To this end, the response to induced hypothyroidism was compared in males from two mouse strains, the wild-derived WSB/EiJ mouse strain characterized by a diet-induced obesity (DIO) resistance due to its high metabolic flexibility phenotype and C57BL/6J mice, which are prone to DIO. The results show that propylthiouracil (PTU)-induced hypothyroidism led to metabolic deregulations, particularly a reduction in hepatic lipid synthesis in both strains. Furthermore, in contrast to the C57BL/6J mice, the WSB/EiJ mice were resistant to the metabolic dysregulations induced by hypothyroidism, mainly through enhanced lipid metabolism in their adipose tissue. Indeed, WSB/EiJ mice compensated for the decrease in hepatic lipid synthesis by mobilizing lipid reserves from white adipose tissue. Gene expression analysis revealed that hypothyroidism stimulated the hypothalamic orexigenic circuit in both strains, but there was unchanged melanocortin 4 receptor (Mc4r) and leptin receptor (LepR) expression in the hypothyroid WSB/EiJ mice strain, which reflects their adaptability to maintain their body weight, in contrast to C57BL/6J mice. Thus, this study showed that WSB/EiJ male mice displayed a resistance to the metabolic dysregulations induced by hypothyroidism through compensatory mechanisms. This highlights the importance of metabolic flexibility in the ability to adapt to disturbed circulating TH levels.
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页数:20
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