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Hypertriglyceridaemia, commonly observed in these patients, compromises macrovascular function. However, the effects of high\u2010fat diet\u2010induced increases in circulating lipids on microvascular remodelling are not established. Here, we investigated if high\u2010fat diet would mimic the detrimental effect of type 2 diabetes on post\u2010ischaemia vascular remodelling and muscle regeneration, using a mouse model of hindlimb ischaemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male C57Bl6\/J mice were fed with normal or high\u2010fat diets for 8\u00a0weeks 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\u00a0at 4 or 14\u00a0days post\u2010ligation by histology and RNA analyses. Capillary\u2010level haemodynamics were assessed by intravital microscopy of control and regenerating muscles 14\u00a0days post\u2010ligation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High\u2010fat diet increased muscle succinate dehydrogenase activity and capillary\u2010level oxygen supply. At 4\u00a0days post\u2010ligation, no diet differences were detected in muscle damage, inflammatory infiltration or capillary activation. At 14\u00a0days post\u2010ligation, high fat\u2010fed mice displayed accelerated limb blood flow recovery, elevated capillary and arteriole densities as well as greater red blood cell supply rates and capillary\u2010level oxygen supply. Regenerating muscles from high fat\u2010fed mice displayed lower interstitial fat and collagen deposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The muscle\u2010level adaptations to high\u2010fat diet improved multiple aspects of muscle recovery in response to ischaemia and did not recapitulate the worse outcomes seen in diabetic CLI patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13449","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T20:21:01Z","timestamp":1580761261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["High\u2010fat diet pre\u2010conditioning improves microvascular remodelling during regeneration of ischaemic mouse skeletal muscle"],"prefix":"10.1111","volume":"229","author":[{"given":"Emmanuel","family":"Nwadozi","sequence":"first","affiliation":[{"name":"School of Kinesiology and Health Science Muscle Health 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