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Metabolic Adaptations in the Liver of Born Long-Distance Running Mice

BRENMOEHL, JULIA1; WALZ, CHRISTINA1; RENNE, ULLA1; PONSUKSILI, SIRILUCK2; WOLF, CAROLA3; LANGHAMMER, MARTINA1; SCHWERIN, MANFRED2,4; HOEFLICH, ANDREAS1

Medicine & Science in Sports & Exercise: May 2013 - Volume 45 - Issue 5 - p 841–850
doi: 10.1249/MSS.0b013e31827e0fca
BASIC SCIENCES: Special Report

Purpose: Long-distance runners have increased needs of energy supply. To unravel genetically based mechanisms required for efficient energy supply, we have analyzed hepatic metabolism of mice characterized by the inborn capacity to perform as long-distance runners.

Methods: The mouse model had been established by phenotypic selection for high treadmill performance for 90 generations and was characterized by approximately 3.8-fold higher running capacities (Dummerstorf high Treadmill Performance mouse line [DUhTP]) compared with unselected and also untrained controls (Dummerstorf Control mouse line [DUC]). From 7-wk-old male mice, serum and liver samples were collected and analyzed for messenger RNA, protein, and metabolite levels, respectively.

Results: In livers from DUhTP mice, we identified significantly higher messenger RNA transcript levels of peroxisome proliferator–activated receptor delta and higher protein levels of sirtuin-1, acetyl-CoA-synthetase, acetyl-CoA-carboxylase, phosphoenolpyruvate carboxykinase, and glutamate-dehydrogenase, suggesting higher gluconeogenesis and lipogenesis in DUhTP mice. In fact, higher hepatic levels of glycogen and triglycerides as well as higher concentrations of carbohydrate, fatty acid, and cholesterol metabolites were found in DUhTP mice. In parallel, in DUhTP mice, which did not have access to running wheels, a marked hyperlipidemia (cholesterol = 160% ± 8%, triglycerides = 174% ± 14% of controls, respectively), and abdominal obesity (DUhTP = 0.396 ± 0.019 g, DUC = 0.291 ± 0.019 g) were found.

Conclusions: From our data, we conclude that the physiological basis of genetically fixed higher endurance-running performance in DUhTP marathon mouse is related to increased hepatic gluconeogenesis and lipogenesis. Expression of sirtuin 1 as well as of gluconeogenic and lipogenic key enzymes may be related to peroxisome proliferator–activated receptor delta. Metabolic adaptations presented in our study represent inborn features of superior endurance-running performance.

1Research Unit of Genetics and Biometry, Leibniz-Institute for Farm Animal Biology, Dummerstorf, GERMANY; 2Research Group Functional Genomics, Leibniz-Institute for Farm Animal Biology, Dummerstorf, GERMANY; 3State Offices for Agriculture, Food Safety and Fishery Mecklenburg–Vorpommern, Rostock, GERMANY; and 4Institute of Farm Animal Sciences and Technology, University of Rostock, Rostock, GERMANY

Address for correspondence: Prof. Dr. Manfred Schwerin, Leibniz-Institute for Farm Animal Biology, Dummerstorf Wilhelm-Stahl-Allee 2 18196, Dummerstorf, Germany; E-mail: schwerin@fbn-dummerstorf.de.

Submitted for publication February 2012.

Accepted for publication November 2012.

©2013The American College of Sports Medicine