Metabolic characteristics of transmembrane prolyl 4-hydroxylase (P4H-TM) deficient mice
Pflugers Arch. 2024 Feb 24. doi: 10.1007/s00424-024-02920-5. Online ahead of print.ABSTRACTTransmembrane prolyl 4-hydroxylase (P4H-TM) is an enigmatic enzyme whose cellular function and primary substrate remain to be identified. Its loss-of-function mutations cause a severe neurological HIDEA syndrome with hypotonia, intellectual disability, dysautonomia and hypoventilation. Previously, P4H-TM deficiency in mice was associated with reduced atherogenesis and lower serum triglyceride levels. Here, we characterized the glucose and lipid metabolism of P4h-tm-/- mice in physiological and tissue analyses. P4h-tm-/- mice showed variations in 24-h oscillations of energy expenditure, VO2 and VCO2 and locomotor activity compared to wild-type (WT) mice. Their rearing activity was reduced, and they showed significant muscle weakness and compromised coordination. Sedated P4h-tm-/- mice had better glucose tolerance, lower fasting insulin levels, higher fasting lactate levels and lower fasting free fatty acid levels compared to WT. These alterations were not present in conscious P4h-tm-/- mice. Fasted P4h-tm-/- mice presented with faster hepatic glycogenolysis. The respiratory rate of conscious P4h-tm-/- mice was significantly lower compared to the WT, the decrease being further exacerbated by sedation and associated with acidosis and a reduced ventilatory response to both hypoxia and hypercapnia. P4H-TM deficiency in mice is associated with alterations in whole-body energy metabolism, day-...
Source: Pflugers Archiv : European Journal of Physiology - Category: Physiology Authors: Tuulia Ala-Nisula Riikka Halmetoja Henri Leinonen Margareta Kurkela Henna-Riikka Lipponen Samuli Sakko Mikko Karpale Antti M Salo Niina Sissala Tapio R öning Ghulam S Raza Kari A M äkelä J érôme Thevenot Karl-Heinz Herzig Raisa Serpi Johanna Myllyhar Source Type: research
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