{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T18:57:27Z","timestamp":1775069847769,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012513","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Cardiovasculares","doi-asserted-by":"publisher","award":["CB16\/11\/00286"],"award-info":[{"award-number":["CB16\/11\/00286"]}],"id":[{"id":"10.13039\/501100012513","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["B2017\/BMD-3676"],"award-info":[{"award-number":["B2017\/BMD-3676"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Juan de la Cierva Program","award":["IJCI-2017-31399"],"award-info":[{"award-number":["IJCI-2017-31399"]}]},{"name":"Italfarmaco, S.A.","award":["L.O.U. 83; 0138\/2018"],"award-info":[{"award-number":["L.O.U. 83; 0138\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available Prodefen\u00ae Plus. MtS was induced by HFD (45%) in male Wistar rats. Half of the MtS animals received Prodefen\u00ae Plus for 4 weeks. At 12 weeks, we observed an increase in body weight, together with the presence of insulin resistance, liver steatosis, hypertriglyceridemia and hypertension in MtS rats. Prodefen\u00ae Plus supplementation did not affect the body weight gain but ameliorated all the MtS-related symptoms. Moreover, the hypertension induced by HFD is caused by a diminished both nitric oxide (NO) functional role and release probably due to a diminished neuronal nitric oxide synthase (nNOS) activation by protein kinase A (PKA) pathway. Prodefen\u00ae Plus supplementation for 4 weeks recovered the NO function and release and the systolic blood pressure was returned to normotensive values as a result. Overall, supplementation with Prodefen\u00ae Plus could be considered an interesting non-pharmacological approach in MtS.<\/jats:p>","DOI":"10.3390\/nu12010117","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T04:43:03Z","timestamp":1578026583000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Beneficial Effect of a Multistrain Synbiotic Prodefen\u00ae Plus on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats: The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase A"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1925-7204","authenticated-orcid":false,"given":"Pablo","family":"Ll\u00e9venes","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine, Universidad Aut\u00f3noma de Madrid, Calle de Arzobispo Morcillo 4, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6348-1505","authenticated-orcid":false,"given":"Raquel","family":"Rodrigues-D\u00edez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Medicine, Universidad Aut\u00f3noma de Madrid, Calle de Arzobispo Morcillo 4, 28029 Madrid, Spain"},{"name":"Center for Biomedical Research Network (CIBER) in Cardiovascular Diseases, Calle de Melchor Fern\u00e1ndez Almagro 3, 28029 Madrid, Spain"},{"name":"Research Institute University Hospital la Paz (IdIPaz), Calle de Pedro Rico 6, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laia","family":"Cros-Bruns\u00f3","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Universidad Aut\u00f3noma de Madrid, Calle de Arzobispo Morcillo 4, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u1d43 Isabel","family":"Prieto","sequence":"additional","affiliation":[{"name":"Research Institute University Hospital la Paz (IdIPaz), Calle de Pedro Rico 6, 28029 Madrid, Spain"},{"name":"Department of General and Digestive Surgery, Hospital Universitario la Paz, Paseo de la Castellana 261, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-4588","authenticated-orcid":false,"given":"Laura","family":"Casan\u00ed","sequence":"additional","affiliation":[{"name":"Research Institute of Santa Creu i Sant Pau Hospital, Carrer de Sant Quint\u00ed 77\u201379, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Balfag\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Universidad Aut\u00f3noma de Madrid, Calle de Arzobispo Morcillo 4, 28029 Madrid, Spain"},{"name":"Center for Biomedical Research Network (CIBER) in Cardiovascular Diseases, Calle de Melchor Fern\u00e1ndez Almagro 3, 28029 Madrid, Spain"},{"name":"Research Institute University Hospital la Paz (IdIPaz), Calle de Pedro Rico 6, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7232-2314","authenticated-orcid":false,"given":"Javier","family":"Blanco-Rivero","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Universidad Aut\u00f3noma de Madrid, Calle de Arzobispo Morcillo 4, 28029 Madrid, Spain"},{"name":"Center for Biomedical Research Network (CIBER) in Cardiovascular Diseases, Calle de Melchor Fern\u00e1ndez Almagro 3, 28029 Madrid, Spain"},{"name":"Research Institute University Hospital la Paz (IdIPaz), Calle de Pedro Rico 6, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0140-6736(18)32822-8","article-title":"The Global Syndemic of Obesity, Undernutrition, and Climate Change: The Lancet Commission report","volume":"393","author":"Swinburn","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1614362","article-title":"Health Effects of Overweight and Obesity in 195 Countries over 25 Years","volume":"377","author":"Collaborators","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.numecd.2012.11.009","article-title":"Factors involved in rosuvastatin induction of insulin sensitization in rats fed a high fat diet","volume":"23","author":"Ballesteros","year":"2013","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1046\/j.1440-1681.2003.t01-1-03808.x","article-title":"Diet-induced obesity and cardiovascular regulation in C57BL\/6J mice","volume":"30","author":"Williams","year":"2003","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00394-018-1790-2","article-title":"Adipose tissue inflammation and metabolic syndrome. The proactive role of probiotics","volume":"58","author":"Torres","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6993","DOI":"10.1038\/s41598-019-43513-y","article-title":"Acute-on-chronic liver disease enhances phenylephrine-induced endothelial nitric oxide release in rat mesenteric resistance arteries through enhanced PKA, PI3K\/AKT and cGMP signalling pathways","volume":"9","author":"Caracuel","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.ejphar.2011.01.007","article-title":"Aldosterone alters the participation of endothelial factors in noradrenaline vasoconstriction differently in resistance arteries from normotensive and hypertensive rats","volume":"654","author":"Xavier","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","first-page":"727","article-title":"Perivascular innervation of the superior mesenteric artery: Pathophysiological implications","volume":"50","author":"Sastre","year":"2010","journal-title":"Rev. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1476-5381.2010.01030.x","article-title":"Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats","volume":"162","author":"Heras","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1097\/HJH.0000000000000627","article-title":"Aerobic exercise training increases nitrergic innervation function and decreases sympathetic innervation function in mesenteric artery from rats fed a high-fat diet","volume":"33","author":"Sastre","year":"2015","journal-title":"J. Hypertens."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11070","DOI":"10.1073\/pnas.0504978102","article-title":"Obesity alters gut microbial ecology","volume":"102","author":"Ley","year":"2005","journal-title":"PNAS"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.bpg.2013.03.007","article-title":"Diabetes, obesity and gut microbiota","volume":"27","author":"Everard","year":"2013","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s13679-019-00352-2","article-title":"Understanding the Role of the Gut Microbiome and Microbial Metabolites in Obesity and Obesity-Associated Metabolic Disorders: Current Evidence and Perspectives","volume":"8","author":"Vallianou","year":"2019","journal-title":"Curr. Obes. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/oby.22175","article-title":"Gut Microbes and Health: A Focus on the Mechanisms Linking Microbes, Obesity, and Related Disorders","volume":"26","author":"Rastelli","year":"2018","journal-title":"Obesity"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3945\/ajcn.110.010132","article-title":"Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans","volume":"94","author":"Jumpertz","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1002\/mnfr.201500290","article-title":"Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats","volume":"59","author":"Toral","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ismej.2014.99","article-title":"Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice","volume":"9","author":"Wang","year":"2015","journal-title":"ISME J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ijfoodmicro.2004.05.012","article-title":"Monostrain, multistrain and multispecies probiotics\u2014A comparison of functionality and efficacy","volume":"96","author":"Timmerman","year":"2004","journal-title":"Int. J. Food Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1017\/S0007114599000471","article-title":"Scientific Concepts of functional Foods in Europe Consensus Document","volume":"81","author":"Diplock","year":"1999","journal-title":"Br. J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Menor, E., Garc\u00eda-Mar\u00edn, F., Vecino-L\u00f3pez, R., Horcajo-Mart\u00ednez, G., de Ibarrondo Guerrica-Echevarr\u00eda, M.J., G\u00f3mez-Gonz\u00e1lez, P., Velasco-Ortega, S., Su\u00e1rez-Almarza, J., and Nieto-Magro, C. (2016). A Multicenter, Prospective, Randomized Controlled Trial to Evaluate the Additional Benefit of a Multistrain Synbiotic (Prodefen\u00ae) in the Clinical Management of Acute Viral Diarrhea in Children. Glob. Pediatr. Health, 3.","DOI":"10.1177\/2333794X16679587"},{"key":"ref_21","first-page":"S298","article-title":"Efficacy of a 7-strain synbiotic mixture in combination with oral antibiotic treatment in preventing antibiotic-associated diarrhoea (AAD). PRODEGGIO study. World Congress of Gastroenterology, Istambul 2019","volume":"30","author":"Romeo","year":"2019","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_22","unstructured":"Blanco-Rivero, J., Ll\u00e9venes, P., and Balfag\u00f3n, G. (2018, January 19\u201321). Supplementation with a synbiotic (Prodefen\u00ae) increases neuronal nitric oxide bioavailability through an enhanced neuronal nitric oxide synthase activation and diminished oxidative stress in superior mesenteric artery from spontaneously hypertensive rats. Proceedings of the 2nd World Congress on Nutrition and Obesity Prevention Source 2018, Valencia, Spain."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4699","DOI":"10.1111\/bph.13244","article-title":"Alterations in perivascular innervation function in mesenteric arteries from offspring of diabetic rats","volume":"172","author":"Queiroz","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Amor, S., Gonz\u00e1lez-Hedstr\u00f6m, D., Mart\u00edn-Carro, B., Inarejos-Garc\u00eda, A.M., Almod\u00f3var, P., Prodanov, M., Garc\u00eda-Villal\u00f3n, A.L., and Granado, M. (2019). Beneficial Effects of an Aged Black Garlic Extract in the Metabolic and Vascular Alterations Induced by a High Fat\/Sucrose Diet in Male Rats. Nutrients, 11.","DOI":"10.3390\/nu11010153"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Knopfholz, J., Disserol, C.C.D., Pierin, A.J., Schirr, F.L., Streisky, L., Takito, L.L., Massucheto Ledesma, P., Faria-Neto, J.R., Olandoski, M., and da Cunha, C.L. (2014). Validation of the Friedewald Formula in Patients with Metabolic Syndrome. Cholesterol, 2014.","DOI":"10.1155\/2014\/261878"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0006-8993(71)90370-2","article-title":"Contractile response and amine receptor mechanisms in isolated middle cerebral artery of the cat","volume":"27","author":"Nielsen","year":"1971","journal-title":"Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.vph.2018.05.001","article-title":"Thyroid hormones affect nitrergic innervation function in rat mesenteric T artery: Role of the PI3K\/AKT pathway","volume":"108","year":"2018","journal-title":"Vascul. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Unger, A.L., Torres-Gonzalez, M., and Kraft, J. (2019). Dairy Fat Consumption and the Risk of Metabolic Syndrome: An Examination of the Saturated Fatty Acids in Dairy. Nutrients, 11.","DOI":"10.3390\/nu11092200"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"619","DOI":"10.4254\/wjh.v11.i8.619","article-title":"Prolonged high-fat-diet feeding promotes non-alcoholic fatty liver disease and alters gut microbiota in mice","volume":"11","author":"Enos","year":"2019","journal-title":"World J. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.5650\/jos.ess19183","article-title":"Dietary fat influences the expression of genes related to sterol metabolism and the composition of cecal microbiota and its metabolites in rats","volume":"68","author":"Hosomi","year":"2019","journal-title":"J. Oleo Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"110576","DOI":"10.1016\/j.nut.2019.110576","article-title":"Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet-induced obese condition","volume":"69","author":"Saiyasit","year":"2019","journal-title":"Nutrition"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1038\/nutd.2016.2","article-title":"A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or \u03b2-cell mass in NZO mice","volume":"6","author":"Lamont","year":"2016","journal-title":"Nutr. Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1039\/C7FO01095H","article-title":"Amentoflavone improves cardiovascular dysfunction and metabolic abnormalities in high fructose and fat diet-fed rats","volume":"9","author":"Qin","year":"2018","journal-title":"Food Funct."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jnutbio.2017.08.006","article-title":"Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice","volume":"50","author":"Bagarolli","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1111\/1462-2920.13181","article-title":"Beneficial metabolic effects of selected probiotics on diet-induced obesity and insulin resistance in mice are associated with improvement of dysbiotic gut microbiota","volume":"18","author":"Alard","year":"2016","journal-title":"Environ. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1042\/CS20130339","article-title":"The probiotic Lactobacillus coryniformis CECT5711 reduces the vascular pro-oxidant and pro-inflammatory status in obese mice","volume":"127","author":"Toral","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1042\/CS20180148","article-title":"Probiotic Lactobacillus paracasei HII01 protects rats against obese-insulin resistance-induced kidney injury and impaired renal organic anion transporter 3 function","volume":"132","author":"Wanchai","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.4158\/EP151157.RA","article-title":"Gut microbiota, prebiotics, probiotics, and synbiotics in management of obesity and prediabetes: Review of randomized controlled trials","volume":"22","author":"Barengolts","year":"2016","journal-title":"Endocr. Pract."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Tenorio-Jim\u00e9nez, C., Mart\u00ednez-Ram\u00edrez, M.J., Castillo-Codes, I.D., Arraiza-Irigoyen, C., Tercero-Lozano, M., Camacho, J., Chueca, N., Garc\u00eda, F., Olza, J., and Plaza-D\u00edaz, J. (2019). Lactobacillus reuteri V3401 Reduces Inflammatory Biomarkers and Modifies the Gastrointestinal Microbiome in Adults with Metabolic Syndrome: The PROSIR Study. Nutrients, 11.","DOI":"10.3390\/nu11081761"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Higarza, S.G., Arboleya, S., Gueimonde, M., G\u00f3mez-L\u00e1zaro, E., Arias, J.L., and Arias, N. (2019). Neurobehavioral dysfunction in non- alcoholic steatohepatitis is associated with hyperammonemia, gut dysbiosis, and metabolic and functional brain regional deficits. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223019"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jnutbio.2013.09.006","article-title":"Effects of a Lactobacillus paracasei B21060 based synbiotic on steatosis, insulin signaling and toll-like receptor expression in rats fed a high-fat diet","volume":"25","author":"Raso","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.5114\/aoms.2019.86611","article-title":"Effect of Lactobacillus paracasei N1115 and fructooligosaccharides in nonalcoholic fatty liver disease","volume":"15","author":"Yao","year":"2019","journal-title":"Arch. Med. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Choi, B.-R., Kwon, E.-Y., Kim, H.-J., and Choi, M.-S. (2018). Role of Synbiotics Containing d-Allulose in the Alteration of Body Fat and Hepatic Lipids in Diet-Induced Obese Mice. Nutrients, 10.","DOI":"10.3390\/nu10111797"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1038\/sj.ijo.0802053","article-title":"Skeletal muscle triglycerides lowering is associated with net improvement of insulin sensitivity, TNF-a reduction and GLUT4 expression enhancement","volume":"26","author":"Mingrone","year":"2002","journal-title":"Int. J. Obes."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1002\/oby.20358","article-title":"Structural and Functional Microvascular Alterations in a Rat Model of Metabolic Syndrome Induced by a High-Fat Diet","volume":"21","author":"Nascimento","year":"2012","journal-title":"Obesity"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrcardio.2017.120","article-title":"Beyond gut feelings: How the gut microbiota regulates blood pressure","volume":"15","author":"Marques","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1042\/CS20110072","article-title":"Chronic HgCl2 treatment increases vasoconstriction induced by electrical field stimulation: Role of adrenergic and nitrergic innervation","volume":"121","author":"Furieri","year":"2011","journal-title":"Clin. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1097\/01.hjh.0000358836.64052.43","article-title":"The protective effect of irbesartan in rats fed a high fat diet is associated with modification of leptin\u2013adiponectin imbalance","volume":"27","author":"Heras","year":"2009","journal-title":"J. Hypertens."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1097\/HJH.0b013e32832531e6","article-title":"Hypertension alters the function of nitrergic and sensory innervation in mesenteric arteries from female rats","volume":"27","author":"Campo","year":"2009","journal-title":"J. Hypertens."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sastre, E., Blanco-Rivero, J., Caracuel, L., Callejo, M.A., and Balfag\u00f3n, G. (2015). Alterations in Perivascular Sympathetic and Nitrergic Innervation Function Induced by Late Pregnancy in Rat Mesenteric Arteries. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126017"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1042\/cs0990277","article-title":"Role of protein kinase C in electrical-stimulation-induced neuronal nitric oxide release in mesenteric arteries from hypertensive rats","volume":"99","author":"Ferrer","year":"2000","journal-title":"Clin. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.1111\/j.1523-1755.2005.00747.x","article-title":"Effect of hereditary obesity on renal expressions of NO synthase, caveolin-1, AKt, guanylate cyclase, and calmodulin","volume":"68","author":"Li","year":"2005","journal-title":"Kidney Int."},{"key":"ref_53","first-page":"65","article-title":"Diet-induced obesity impairs AKT signalling in the retina and causes retinal degeneration","volume":"31","author":"Leonelli","year":"2012","journal-title":"Cell Biochem. Funct."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.bbrc.2005.10.039","article-title":"Altered expression of neuronal nitric oxide synthase in the duodenum longitudinal muscle\u2013myenteric plexus of obesity induced diabetes mouse: Implications on enteric neurodegeneration","volume":"338","author":"Surendran","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Rashid, S.K., Khodja, N.I., Auger, C., Alhosin, M., Boehm, N., Oswald-Mammosser, M., and Schini-Kerth, V.B. (2014). Probiotics (VSL#3) Prevent Endothelial Dysfunction in Rats with Portal Hypertension: Role of the Angiotensin System. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097458"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Suo, H., Zhao, X., Qian, Y., Sun, P., Zhu, K., Li, J., and Sun, B. (2016). Lactobacillus fermentum Suo Attenuates HCl\/Ethanol Induced Gastric Injury in Mice through Its Antioxidant Effects. Nutrients, 8.","DOI":"10.3390\/nu8030155"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/978-3-319-48382-5_5","article-title":"Human Protein Kinases and Obesity","volume":"960","author":"Engin","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s11011-017-9962-y","article-title":"Effects of obesity on protein kinase C, brain creatine kinase, transcription, and autophagy in cochlea","volume":"32","author":"Hwang","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41398-019-0470-1","article-title":"A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling","volume":"9","author":"Vagena","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.3748\/wjg.v18.i30.3977","article-title":"Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice","volume":"18","author":"Zhou","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3945\/jn.109.114553","article-title":"A Bifidobacterium Probiotic Strain and Its Soluble Factors Alleviate Chloride Secretion by Human Intestinal Epithelial Cells","volume":"140","author":"Heuvelin","year":"2009","journal-title":"J. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1017\/S0007114515002469","article-title":"Supplementary heat-killed Lactobacillus reuteri GMNL-263 ameliorates hyperlipidaemic and cardiac apoptosis in high-fat diet-fed hamsters to maintain cardiovascular function","volume":"114","author":"Ting","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3920\/BM2017.0107","article-title":"Lactobacillus fermentum L930BB and Bifidobacterium animalis subsp. animalis IM386 initiate signalling pathways involved in intestinal epithelial barrier protection","volume":"9","author":"Juvan","year":"2018","journal-title":"Benef. Microbes"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.molimm.2018.09.001","article-title":"Probiotics SOD inhibited food allergy via downregulation of STAT6-TIM4 T signaling on DCs","volume":"103","author":"Yang","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s13287-019-1324-8","article-title":"Lactobacillus reuteri extracts promoted wound healing via PI3K\/AKT\/\u03b2-catenin\/TGF\u03b21 pathway","volume":"10","author":"Han","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Kumar, R., Sharma, A., Gupta, M., Padwad, Y., and Sharma, R. (2019). Cell-Free Culture Supernatant of Probiotic Lactobacillus fermentum Protects Against H2O2-Induced Premature Senescence by Suppressing ROS-Akt-mTOR Axis in Murine Preadipocytes. Probiotics Antimicrob. Proteins, 1\u201314.","DOI":"10.1007\/s12602-019-09576-z"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ejphar.2004.01.030","article-title":"Protein kinase A increases electrical stimulation-induced neuronal nitric oxide release in rat mesenteric artery","volume":"487","author":"Ferrer","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1159\/000088342","article-title":"Male Castration Increases Neuronal Nitric Oxide Synthase Activity in the Rat Mesenteric Artery through Protein Kinase C Activation","volume":"42","author":"Ferrer","year":"2005","journal-title":"J. Vasc. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1203\/PDR.0b013e3181d4ff2b","article-title":"Effects of probiotics, prebiotics, and synbiotics on messenger RNA expression of caveolin-1, NOS, and genes regulating oxidative stress in the terminal ileum of formula-fed neonatal rats","volume":"67","author":"Fordjour","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1161\/01.RES.82.12.1298","article-title":"Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis","volume":"82","author":"Miller","year":"1998","journal-title":"Circ. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/01.RES.82.7.810","article-title":"Superoxide anion from the adventitia of the rat thoracic aorta inactivates nitric oxide","volume":"82","author":"Wang","year":"1998","journal-title":"Circ. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.atherosclerosis.2014.09.001","article-title":"Vascular oxidative stress, nitric oxide and atherosclerosis","volume":"237","author":"Li","year":"2014","journal-title":"Atherosclerosis"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/1\/117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:03:27Z","timestamp":1760364207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/1\/117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,1]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["nu12010117"],"URL":"https:\/\/doi.org\/10.3390\/nu12010117","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,1]]}}}