title: Running performance at high running velocities is impaired but V'O(₂max) and peripheral endothelial function are preserved in IL-6⁻/⁻ mice.
abstract: It has been reported that IL-6 knockout mice (IL-6⁻/⁻) possess lower endurance capacity than wild type mice (WT), however the underlying mechanism is poorly understood. The aim of the present work was to examine whether reduced endurance running capacity in IL-6⁻/⁻ mice is linked to impaired maximal oxygen uptake (V'O(₂max)), decreased glucose tolerance, endothelial dysfunction or other mechanisms. Maximal running velocity during incremental running to exhaustion was significantly lower in IL-6⁻/⁻ mice than in WT mice (13.00±0.97 m·min⁻¹ vs. 16.89±1.15 m·min⁻¹, P<0.02, respectively). Moreover, the time to exhaustion during running at 12 m·min⁻¹ in IL-6⁻/⁻ mice was significantly shorter (P<0.05) than in WT mice. V'O(₂max) in IL-6⁻/⁻ (n = 20) amounting to 108.3±2.8 ml·kg⁻¹·min⁻¹ was similar as in WT mice (n = 22) amounting to 113.0±1.8 ml·kg⁻¹·min⁻¹, (P = 0.16). No difference in maximal COX activity between the IL-6⁻/⁻ and WT mice in m. soleus and m. gastrocnemius was found. Moreover, no impairment of peripheral endothelial function or glucose tolerance was found in IL-6⁻/⁻ mice. Surprisingly, plasma lactate concentration during running at 8 m·min⁻¹ as well at maximal running velocity in IL-6⁻/⁻ mice was significantly lower (P<0.01) than in WT mice. Interestingly, IL-6⁻/⁻ mice displayed important adaptive mechanisms including significantly lower oxygen cost of running at a given speed accompanied by lower expression of sarcoplasmic reticulum Ca²⁺-ATPase and lower plasma lactate concentrations during running at submaximal and maximal running velocities. In conclusion, impaired endurance running capacity in IL-6⁻/⁻ mice could not be explained by reduced V'O(₂max), endothelial dysfunction or impaired muscle oxidative capacity. Therefore, our results indicate that IL-6 cannot be regarded as a major regulator of exercise capacity but rather as a modulator of endurance performance. Furthermore, we identified important compensatory mechanism limiting reduced exercise performance in IL-6⁻/⁻ mice.
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Wojewoda
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kmiecik
authors.affiliation: U-769, INSERM, Université Paris-Sud, Châtenay-Malabry, France.
authors.forename: Renée
authors.initials: R
authors.lastname: Ventura-Clapier
authors.affiliation: U-769, INSERM, Université Paris-Sud, Châtenay-Malabry, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Fortin
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Onopiuk
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Jakubczyk
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fedorowicz
authors.affiliation: Department of Muscle Physiology, University School of Physical Education, Krakow, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Majerczak
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Kaminski
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
authors.affiliation: Department of Muscle Physiology, University School of Physical Education, Krakow, Poland.
authors.forename: Jerzy Andrzej
authors.initials: JA
authors.lastname: Zoladz
mesh_terms: D000818:Animals; D001831:Body Temperature; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004727:Endothelium / Q000502:physiology*; D017079:Exercise Tolerance; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D015850:Interleukin-6 / Q000235:genetics*; D007473:Ion Channels / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption; D010805:Physical Conditioning, Animal; D010807:Physical Endurance / Q000235:genetics*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D000071247:Uncoupling Protein 3
chemical_list: D015850:Interleukin-6; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071247:Uncoupling Protein 3; C577686:interleukin-6, mouse; D019344:Lactic Acid; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D005947:Glucose