High-fat diet pre-conditioning improves microvascular remodelling during regeneration of ischaemic mouse skeletal muscle.

Autor: Nwadozi E; School of Kinesiology and Health Science, Muscle Health Research Centre, Angiogenesis Research Group, York University, Toronto, ON, Canada., Rudnicki M; School of Kinesiology and Health Science, Muscle Health Research Centre, Angiogenesis Research Group, York University, Toronto, ON, Canada., De Ciantis M; School of Kinesiology and Health Science, Muscle Health Research Centre, Angiogenesis Research Group, York University, Toronto, ON, Canada., Milkovich S; Department of Medical Biophysics, University of Western Ontario, London, ON, Canada., Pulbere A; School of Kinesiology and Health Science, Muscle Health Research Centre, Angiogenesis Research Group, York University, Toronto, ON, Canada., Roudier E; School of Kinesiology and Health Science, Muscle Health Research Centre, Angiogenesis Research Group, York University, Toronto, ON, Canada., Birot O; School of Kinesiology and Health Science, Muscle Health Research Centre, Angiogenesis Research Group, York University, Toronto, ON, Canada., Gustafsson T; Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.; Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden., Ellis CG; Department of Medical Biophysics, University of Western Ontario, London, ON, Canada., Haas TL; School of Kinesiology and Health Science, Muscle Health Research Centre, Angiogenesis Research Group, York University, Toronto, ON, Canada.
Jazyk: angličtina
Zdroj: Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2020 May; Vol. 229 (1), pp. e13449. Date of Electronic Publication: 2020 Feb 23.
DOI: 10.1111/apha.13449
Abstrakt: Aim: Critical limb ischaemia (CLI) is characterized by inadequate angiogenesis, arteriolar remodelling and chronic myopathy, which are most severe in type 2 diabetic patients. Hypertriglyceridaemia, commonly observed in these patients, compromises macrovascular function. However, the effects of high-fat diet-induced increases in circulating lipids on microvascular remodelling are not established. Here, we investigated if high-fat diet would mimic the detrimental effect of type 2 diabetes on post-ischaemia vascular remodelling and muscle regeneration, using a mouse model of hindlimb ischaemia.
Methods: Male C57Bl6/J mice were fed with normal or high-fat diets for 8 weeks prior to unilateral femoral artery ligation. Laser doppler imaging was used to assess limb perfusion recovery. Vascular recovery, inflammation, myofibre regeneration and fibrosis were assessed at 4 or 14 days post-ligation by histology and RNA analyses. Capillary-level haemodynamics were assessed by intravital microscopy of control and regenerating muscles 14 days post-ligation.
Results: High-fat diet increased muscle succinate dehydrogenase activity and capillary-level oxygen supply. At 4 days post-ligation, no diet differences were detected in muscle damage, inflammatory infiltration or capillary activation. At 14 days post-ligation, high fat-fed mice displayed accelerated limb blood flow recovery, elevated capillary and arteriole densities as well as greater red blood cell supply rates and capillary-level oxygen supply. Regenerating muscles from high fat-fed mice displayed lower interstitial fat and collagen deposition.
Conclusion: The muscle-level adaptations to high-fat diet improved multiple aspects of muscle recovery in response to ischaemia and did not recapitulate the worse outcomes seen in diabetic CLI patients.
(© 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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