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Institutet","award":["2022-01146"],"award-info":[{"award-number":["2022-01146"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: The prevalence of cardiovascular-kidney-metabolic (CKM) syndrome is increasing rapidly, and cardiovascular complications pose significant risks in individuals with kidney disease and metabolic dysfunction. Understanding the mechanisms of CKM disorders is crucial, as is the discovery of novel preventive treatments. This study aimed to examine the therapeutic effects of a specially formulated nitric oxide-enhancing food additive in a mouse model of CKM syndrome induced by unilateral nephrectomy (UNX) in combination with chronic Western diet (WD) feeding. Methods: C57BL\/6J mice underwent UNX and were fed a WD high in salt, sugar, and fat for 12 weeks, compared to sham-operated mice on standard chow. One group of UNX+WD mice received Flexovital (FLX), a food additive containing extracts of Rhodiola rosea and beetroot, and the amino acids L-arginine and L-citrulline. CKM parameters were assessed both in vivo and ex vivo alongside histological and biochemical analyses. Results: The UNX+WD mice showed an increase in body fat mass, the fat\/lean mass ratio, and adipocyte area, of which most were significantly reduced by FLX. Elevated fasting glucose levels were also reduced by FLX, which tended towards improving glucose clearance. Elevated arterial blood pressure and endothelial dysfunction in UNX+WD mice were significantly reduced by FLX. FLX improved GFR and reduced glomerular and tubular injuries in UNX+WD mice. Additionally, FLX increased the P\/O ratios of oxidative phosphorylation in the isolated renal mitochondria of UNX+WD mice. Conclusions: In this model of CKM syndrome, FLX effectively prevented the onset and progression of CKM dysfunctions induced by UNX+WD, as well as the associated organ injuries. These promising results highlight the need for validation in upcoming human trials.<\/jats:p>","DOI":"10.3390\/nu16234105","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T05:19:39Z","timestamp":1732771179000},"page":"4105","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Protective Effects of the Food Supplement Flexovital in a Model of Cardiovascular-Kidney-Metabolic Syndrome in Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-8573","authenticated-orcid":false,"given":"Lucas","family":"Carvalho","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6887-610X","authenticated-orcid":false,"given":"Maria","family":"Tyd\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Nephrology, Uppsala University, 75236 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Shimari","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengbing","family":"Zhuge","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Schiffer","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7199-8053","authenticated-orcid":false,"given":"Matheus","family":"de Oliveira Monteiro","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Lundberg","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"Weitzberg","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4548-702X","authenticated-orcid":false,"given":"Daniel","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 17165 Solna, Sweden"},{"name":"Cardiology Unit, Theme for Heart, Vascular and Neuro, Karolinska University Hospital, 17164 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt","family":"Fellstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Nephrology, Uppsala University, 75236 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9923-8729","authenticated-orcid":false,"given":"Mattias","family":"Carlstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"ref_1","unstructured":"National Kidney Foundation (2002). 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