{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T10:52:48Z","timestamp":1769165568829,"version":"3.49.0"},"reference-count":93,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T00:00:00Z","timestamp":1582848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy metabolism and vascular function. The main objective of this study was to analyze the role of dietary fats on hepatic peptidases activities and metabolic disorders. Three diets: standard (S), HFD supplemented with virgin olive oil (VOO), and HFD supplemented with butter plus cholesterol (Bch), were administered over six months to male Wistar rats. Plasma and liver samples were collected for clinical biochemistry and aminopeptidase activities (AP) analysis. The expression of inducible nitric oxide synthase (iNOS) was also determined by Western blot in liver samples. The diet supplement with VOO did not induce obesity, in contrast to the Bch group. Though the VOO diet increased the time that was needed to return to the basal levels of plasma glucose, the fasting insulin\/glucose ratio and HOMA2-%B index (a homeostasis model index of insulin secretion and valuation of \u03b2-cell usefulness (% \u03b2-cell secretion)) were improved. An increase of hepatic membrane-bound dipeptidyl-peptidase 4 (DPP4) activity was found only in VOO rats, even if no differences in fasting plasma glucagon-like peptide 1 (GLP-1) were obtained. Both HFDs induced changes in hepatic pyroglutamyl-AP in the soluble fraction, but only the Bch diet increased the soluble tyrosyl-AP. Angiotensinase activities that are implicated in the metabolism of angiotensin II (AngII) to AngIV increased in the VOO diet, which was in agreement with the higher activity of insulin-regulated-AP (IRAP) in this group. Otherwise, the diet that was enriched with butter increased soluble gamma-glutamyl transferase (GGT) and Leucyl-AP, iNOS expression in the liver, and plasma NO. In summary, VOO increased the hepatic activity of AP that were related to glucose metabolism (DPP4, angiotensinases, and IRAP). However, the Bch diet increased activities that are implicated in the control of food intake (Tyrosine-AP), the index of hepatic damage (Leucine-AP and GGT), and the expression of hepatic iNOS and plasma NO. Taken together, these results support that the source of fat in the diet affects several peptidases activities in the liver, which could be related to alterations in feeding behavior and glucose metabolism.<\/jats:p>","DOI":"10.3390\/nu12030636","type":"journal-article","created":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T09:30:36Z","timestamp":1582882236000},"page":"636","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Role of High Fat Diets and Liver Peptidase Activity in the Development of Obesity and Insulin Resistance in Wistar Rats"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-9148","authenticated-orcid":false,"given":"Germ\u00e1n","family":"Dom\u00ednguez-V\u00edas","sequence":"first","affiliation":[{"name":"Unit of Physiology, Department of Health Sciences, University of Ja\u00e9n, Las Lagunillas, 23071 Ja\u00e9n, Spain"},{"name":"Department of Physiology, Faculty of Health Sciences, Ceuta, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9409-6052","authenticated-orcid":false,"given":"Ana Bel\u00e9n","family":"Segarra","sequence":"additional","affiliation":[{"name":"Unit of Physiology, Department of Health Sciences, University of Ja\u00e9n, Las Lagunillas, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Ram\u00edrez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Unit of Physiology, Department of Health Sciences, University of Ja\u00e9n, Las Lagunillas, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0624-9504","authenticated-orcid":false,"given":"Isabel","family":"Prieto","sequence":"additional","affiliation":[{"name":"Unit of Physiology, Department of Health Sciences, University of Ja\u00e9n, Las Lagunillas, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1210\/jc.2011-2525","article-title":"Regulation of Food Intake, Energy Balance, and Body Fat Mass: Implications for the Pathogenesis and Treatment of Obesity","volume":"97","author":"Guyenet","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/S0140-6736(05)66378-7","article-title":"The metabolic syndrome","volume":"365","author":"Eckel","year":"2005","journal-title":"Lancet"},{"key":"ref_3","first-page":"97S","article-title":"The Obesity Epidemic: Pathophysiology and Consequences of Obesity","volume":"10","year":"2002","journal-title":"Obes. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1017\/S0954422410000168","article-title":"High-fat diet-induced obesity in animal models","volume":"23","author":"Hariri","year":"2010","journal-title":"Nutr. Res. Rev."},{"key":"ref_5","first-page":"664","article-title":"Influence of Extra Virgin Olive Oil on Blood Pressure and Kidney Angiotensinase Activities in Spontaneously Hypertensive Rats","volume":"81","author":"Villarejo","year":"2015","journal-title":"Planta Medica"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gao, M., Ma, Y., and Liu, D. (2015). High-Fat Diet-Induced Adiposity, Adipose Inflammation, Hepatic Steatosis and Hyperinsulinemia in Outbred CD-1 Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119784"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1210\/en.2014-2037","article-title":"Vitamin D Deficiency Attenuates High-Fat Diet-Induced Hyperinsulinemia and Hepatic Lipid Accumulation in Male Mice","volume":"156","author":"Liu","year":"2015","journal-title":"Endocrinology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1210\/en.2015-1015","article-title":"The Flower Tea Coreopsis tinctoria Increases Insulin Sensitivity and Regulates Hepatic Metabolism in Rats Fed a High-Fat Diet","volume":"156","author":"Jiang","year":"2015","journal-title":"Endocrinology"},{"key":"ref_9","first-page":"1566","article-title":"Oleuropein, a component of extra virgin olive oil, lowers postprandial glycaemia in healthy subjects","volume":"84","author":"Carnevale","year":"2018","journal-title":"BJCP"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez-V\u00edas, G., Segarra, A., Mart\u00ednez-Ca\u00f1amero, M., Ram\u00edrez-S\u00e1nchez, M., and Prieto, I. (2017). Influence of a virgin olive oil versus butter plus cholesterol-enriched diet on testicular enzymatic activities in adult male rats. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081701"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez, N., Prieto, I., Hidalgo, M., Segarra, A.B., Mart\u00ednez-Rodr\u00edguez, A., Cobo, A., Ram\u00edrez, M., G\u00e1lvez, A., and Mart\u00ednez-Ca\u00f1amero, M. (2019). Refined versus Extra Virgin Olive Oil High-Fat Diet Impact on Intestinal Microbiota of Mice and Its Relation to Different Physiological Variables. Microorganisms, 7.","DOI":"10.3390\/microorganisms7020061"},{"key":"ref_12","first-page":"4","article-title":"Extra Virgin Olive Oil and Cardiovascular Diseases: Benefits for Human Health","volume":"18","author":"Nocella","year":"2017","journal-title":"Endocr. Metab. Immune"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Prieto, I., Hidalgo, M., Segarra, A.B., Mart\u00ednez-Rodr\u00edguez, A.M., Cobo, A., Ram\u00edrez, M., Abriouel, H., G\u00e1lvez, A., and Mart\u00ednez-Ca\u00f1amero, M. (2018). Influence of a diet enriched with virgin olive oil or butter on mouse gut microbiota and its correlation to physiological and biochemical parameters related to metabolic syndrome. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0190368"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Romani, A., Ieri, F., Urciuoli, S., Noce, A., Marrone, G., Nediani, C., and Bernini, R. (2019). Health Effects of Phenolic Compounds Found in Extra-Virgin Olive Oil, By-Products, and Leaf of Olea europaea L.. Nutrients, 11.","DOI":"10.3390\/nu11081776"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41430-018-0304-x","article-title":"Extra virgin olive oil: More than a healthy fat","volume":"72","year":"2019","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/978-3-319-48382-5_26","article-title":"Lipotoxicity in Obesity: Benefit of Olive Oil","volume":"960","author":"Elias","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1385\/ENDO:26:2:107","article-title":"Effects of an olive oil-enriched diet on plasma GLP-1 concentration and intestinal content, plasma insulin concentration, and glucose tolerance in normal rats","volume":"26","author":"Prieto","year":"2005","journal-title":"Endocrine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1210\/jcem-63-2-492","article-title":"Incretin Effects of Increasing Glucose Loads in Man Calculated from Venous Insulin and C-Peptide Responses*","volume":"63","author":"Nauck","year":"1986","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/BF02427280","article-title":"Reduced incretin effect in type 2 (non-insulin-dependent) diabetes","volume":"29","author":"Nauck","year":"1986","journal-title":"Diabetologia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nrendo.2009.48","article-title":"Incretin-based therapies for type 2 diabetes mellitus","volume":"5","author":"Lovshin","year":"2009","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.2337\/db09-1414","article-title":"The glucagonostatic and insulinotropic effects of glucagon-like peptide 1 contribute equally to its glucose-lowering action","volume":"59","author":"Hare","year":"2010","journal-title":"Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1111\/j.1432-1033.1993.tb17986.x","article-title":"Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum","volume":"214","author":"Mentlein","year":"1993","journal-title":"Eur. J. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1055\/s-2004-814222","article-title":"Glucagon-like Peptide 1 (GLP-1) Secretion and Plasma Dipeptidyl Peptidase IV (DPP-IV) Activity in Morbidly Obese Patients Undergoing Biliopancreatic Diversion","volume":"36","author":"Lugari","year":"2004","journal-title":"Horm. Metab. Res."},{"key":"ref_24","unstructured":"Barrett, A.J., Rawlings, N.D., and Woessner, J.F. (2004). Handbook of Proteolytic Enzymes, Elsevier Academic Press."},{"key":"ref_25","unstructured":"Pbmwm, T., and Wexler, R.R. (1994). Heterogeneity of Angiotensin Receptor Subtypes. Medicinal Chemistry of the Renin-Angiotensin System, Elsevier."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1677\/joe.0.1540133","article-title":"Characterization of the AT1 angiotensin II receptor expressed in guinea pig liver","volume":"154","year":"1997","journal-title":"J. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1007\/s00018-004-4246-1","article-title":"What\u2019s new in the renin-angiotensin system? The angiotensin IV\/AT4 receptor","volume":"61","author":"Chai","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0196-9781(97)00291-X","article-title":"Autoradiographic identification of kidney angiotensin IV binding sites and angiotensin IV-induced renal cortical blood flow changes in rats","volume":"19","author":"Coleman","year":"1998","journal-title":"Peptides"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1055\/s-2008-1046800","article-title":"Dietary Fat Influences Testosterone, Cholesterol, Aminopeptidase A, and Blood Pressure in Male Rats","volume":"40","author":"Segarra","year":"2008","journal-title":"Horm. Metab. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1055\/s-0030-1269855","article-title":"The Profile of Fatty Acids in Frontal Cortex of Rats Depends on the Type of Fat Used in the Diet and Correlates with Neuropeptidase Activities","volume":"43","author":"Segarra","year":"2011","journal-title":"Horm. Metab. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.peptides.2014.10.005","article-title":"The role of renin-angiotensin system modulation on treatment and prevention of liver diseases","volume":"62","author":"Feltenberger","year":"2014","journal-title":"Peptides"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"G691","DOI":"10.1152\/ajpgi.00116.2014","article-title":"Activation of the renin-angiotensin system stimulates biliary hyperplasia during cholestasis induced by extrahepatic bile duct ligation","volume":"308","author":"Afroze","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000329926","article-title":"Possible Mechanisms of Local Tissue Renin-Angiotensin System Activation in the Cardiorenal Metabolic Syndrome and Type 2 Diabetes Mellitus","volume":"1","author":"Hayden","year":"2011","journal-title":"Cardiorenal Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.ejphar.2007.11.016","article-title":"Cross talk of tumor necrosis factor-alpha and the renin-angiotensin system in tumor necrosis factor-alpha-induced plasminogen activator inhibitor-1 production from hepatocytes","volume":"579","author":"Takeshita","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00508-014-0661-y","article-title":"Nonalcoholic fatty liver disease and the renin-angiotensin system blockers in the patients with chronic kidney disease","volume":"127","author":"Orlic","year":"2015","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1194\/jlr.M093252","article-title":"Angiotensinogen in hepatocytes contributes to Western diet-induced liver steatosis","volume":"60","author":"Tao","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_37","first-page":"18","article-title":"Pathways of hepatic and renal damage through non-classical activation of the renin-angiotensin system in chronic liver disease","volume":"40","author":"Aragno","year":"2019","journal-title":"Liver Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biocel.2006.07.001","article-title":"Free radicals and antioxidants in normal physiological functions and human disease","volume":"39","author":"Valko","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s13105-013-0250-y","article-title":"Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet","volume":"69","author":"Abbas","year":"2013","journal-title":"J. Physiol. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1007\/s12020-014-0384-x","article-title":"Adipogenic changes of hepatocytes in a high-fat diet-induced fatty liver mice model and non-alcoholic fatty liver disease patients","volume":"48","author":"Pan","year":"2015","journal-title":"Endocrine"},{"key":"ref_41","first-page":"766","article-title":"Inducible nitric oxide synthase in the liver: Regulation and function","volume":"63","author":"Taylor","year":"1998","journal-title":"Biochemistry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0167-0115(91)90036-G","article-title":"Ontogeny of two topologically distinct TRH-degrading pyroglutamate aminopeptidase activities in the rat liver","volume":"32","author":"Scharfmann","year":"1991","journal-title":"Regul. Pept."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1007\/s12257-011-0618-1","article-title":"Hypoglycemic effects of Cyclo (His-Pro) in streptozotocin-induced diabetic rats","volume":"17","author":"Ra","year":"2012","journal-title":"Biotechnol. Bioproc. E"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1046\/j.1365-2605.2002.0334a.x","article-title":"Dietary fatty acid composition affects aminopeptidase activities in the testes of mice","volume":"25","author":"Arechaga","year":"2002","journal-title":"Int. J. Androl."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1038\/npp.2015.67","article-title":"Involvement of Endogenous Enkephalins and \u03b2-Endorphin in Feeding and Diet-Induced Obesity","volume":"40","author":"Mendez","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_46","first-page":"261","article-title":"Met-enkephalin in the liver as a marker of hepatocellular damage in chronic viral hepatitis type B and C","volume":"51","author":"Mach","year":"2006","journal-title":"Adv. Med. Sci. Poland"},{"key":"ref_47","first-page":"461","article-title":"Met-enkephalin plasma concentration and content in liver tissue in patients with primary biliary cirrhosis","volume":"60","author":"Owczarek","year":"2003","journal-title":"Przegl. Lek."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.brainres.2009.08.001","article-title":"Circulating triglycerides after a high-fat meal: Predictor of increased caloric intake, orexigenic peptide expression, and dietary obesity","volume":"1298","author":"Karatayev","year":"2009","journal-title":"Brain. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/10641960500468326","article-title":"The Effect of High Fat-Induced Obesity on Cardiovascular and Physical Activity and Opioid Responsiveness in Conscious Rats","volume":"28","author":"Dunbar","year":"2006","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0196-9781(01)00622-2","article-title":"Peptidase activities in human semen","volume":"23","author":"Valdivia","year":"2002","journal-title":"Peptides"},{"key":"ref_51","unstructured":"(2019, December 14). HOMA2 Calculator: Overview. The Oxford Centre for diabetes endocrinoly and metabolism. Diabetes Trials Unit, HOMA Calculator. (n.d.). Available online: https:\/\/www.dtu.ox.ac.uk\/homacalculator\/."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0196-9781(94)00186-3","article-title":"Properties of rat brain dipeptidyl aminopeptidases in the presence of detergents","volume":"16","author":"Alba","year":"1995","journal-title":"Peptides"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/978-1-61779-310-3_18","article-title":"Neuropeptidases","volume":"789","author":"Prieto","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/01485010252869333","article-title":"Effects of dietary supplementation with fish oil, lard, or coconut oil on oxytocinase activity in the testis of mice","volume":"48","author":"Segarra","year":"2002","journal-title":"Arch. Androl."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3390\/metabo5040733","article-title":"Bioactive Plant Metabolites in the Management of Non-Communicable Metabolic Diseases: Looking at Opportunities beyond the Horizon","volume":"5","author":"Prasad","year":"2015","journal-title":"Metabolites"},{"key":"ref_57","first-page":"84","article-title":"Thyroid status regulates particulate but not soluble TRH-degrading pyroglutamate aminopeptidase activity in the rat liver","volume":"123","author":"Scharfmann","year":"1990","journal-title":"Acta Endocrinol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E546","DOI":"10.1152\/ajpendo.1995.268.4.E546","article-title":"Dietary fat and adiposity: A dose-response relationship in adult male rats fed isocalorically","volume":"268","author":"Boozer","year":"1995","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/oby.2002.130","article-title":"Fat Intake Affects Adiposity, Comorbidity Factors, and Energy Metabolism of Sprague-Dawley Rats","volume":"10","author":"Ghibaudi","year":"2002","journal-title":"Obes. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S263","DOI":"10.1038\/oby.2001.129","article-title":"Control of Food Intake in the Obese","volume":"9","author":"Blundell","year":"2001","journal-title":"Obes. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1079\/BJN2003000968","article-title":"Effect of high-fat feeding on metabolic efficiency and mitochondrial oxidative capacity in adult rats","volume":"90","author":"Iossa","year":"2003","journal-title":"Br. J. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"769","DOI":"10.2174\/138161211795428948","article-title":"Mediterranean diet rich in olive oil and obesity, metabolic syndrome and diabetes mellitus","volume":"17","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/ejcn.2009.65","article-title":"Incidence of obesity is lower in persons who consume olive oil","volume":"63","author":"Soriguer","year":"2009","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1017\/S0007114518001332","article-title":"Metabolic responses to high-fat diets rich in MUFA v. PUFA","volume":"120","author":"Polley","year":"2018","journal-title":"Br. J. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Shin, S., and Ajuwon, K.M. (2018). Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets. Nutrients, 10.","DOI":"10.3390\/nu10020256"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.jnutbio.2006.11.009","article-title":"Extra virgin olive oil increases uncoupling protein 1 content in brown adipose tissue and enhances noradrenaline and adrenaline secretions in rats","volume":"18","author":"Kawada","year":"2007","journal-title":"J. Nutr. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Castro-Barquero, S., Lamuela-Ravent\u00f3s, R.M., Dom\u00e9nech, M., and Estruch, R. (2018). Relationship between Mediterranean Dietary Polyphenol Intake and Obesity. Nutrients, 10.","DOI":"10.3390\/nu10101523"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Durillo, F., Segarra, A.B., Villarejo, A., Ram\u00edrez-S\u00e1nchez, M., and Prieto, I. (2018). Influence of Diet and Gender on Plasma DPP4 Activity and GLP-1 in Patients with Metabolic Syndrome: An Experimental Pilot Study. Molecules, 23.","DOI":"10.3390\/molecules23071564"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1055\/s-2006-925126","article-title":"Effects of an olive oil-enriched diet on glucagon-like peptide 1 release and intestinal content, plasma insulin concentration, glucose tolerance and pancreatic insulin content in an animal model of type 2 diabetes","volume":"38","author":"Cancelas","year":"2006","journal-title":"Horm. Metab. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1210\/endo.142.3.8034","article-title":"Monounsaturated fatty acid diets improve glycemic tolerance through increased secretion of glucagon-like peptide-1","volume":"142","author":"Rocca","year":"2001","journal-title":"Endocrinology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.metabol.2005.05.014","article-title":"Raw vegetable food containing high cyclo (his-pro) improved insulin sensitivity and body weight control","volume":"54","author":"Song","year":"2005","journal-title":"Metabolism"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1046\/j.1463-1326.2003.00281.x","article-title":"Effects of cyclo (his-pro) plus zinc on glucose metabolism in genetically diabetic obese mice","volume":"5","author":"Hwang","year":"2003","journal-title":"Diabetes Obes. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.1210\/en.2010-0026","article-title":"High-Fat Diet Increases Thyrotropin and Oxygen Consumption without Altering Circulating 3,5,3\u2032-Triiodothyronine (T3) and Thyroxine in Rats: The Role of Iodothyronine Deiodinases, Reverse T3 Production, and Whole-Body Fat Oxidation","volume":"151","author":"Araujo","year":"2010","journal-title":"Endocrinology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.mehy.2007.06.022","article-title":"Liver derived endogenous opioids may interfere with the therapeutic effect of interferon in chronic hepatitis C","volume":"70","author":"Bergasa","year":"2008","journal-title":"Med. Hypotheses"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.taap.2018.09.015","article-title":"Met-enkephalin improves metabolic syndrome in high fat diet challenged mice through promotion of adipose tissue browning","volume":"359","author":"Suo","year":"2018","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"30731","DOI":"10.1074\/jbc.271.48.30731","article-title":"Molecular cloning and expression of rat liver aminopeptidase B","volume":"271","author":"Fukasawa","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1071\/R97055","article-title":"Immunohistochemical localization of placental leucine aminopeptidase\/oxytocinase in normal human placental, fetal and adult tissues","volume":"9","author":"Nagasaka","year":"1997","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3904\/kjim.2017.317","article-title":"Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension","volume":"33","author":"Shim","year":"2018","journal-title":"Korean J. Intern. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"van den Hoven, A.F., Smits, M.L.J., Rosenbaum, C.E.N.M., Verkooijen, H.M., van den Bosch, M.A.A.J., and Lam, M.G.E.H. (2014). The effect of intra-arterial angiotensin II on the hepatic tumor to non-tumor blood flow ratio for radioembolization: A systematic review. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086394"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"359","DOI":"10.4254\/wjh.v11.i4.359","article-title":"Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model","volume":"11","author":"Miranda","year":"2019","journal-title":"World J. Hepatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0167-0115(00)00162-2","article-title":"Effects of des-aspartate-angiotensin I on angiotensin II-induced incorporation of phenylalanine and thymidine in cultured rat cardiomyocytes and aortic smooth muscle cells","volume":"95","author":"Min","year":"2000","journal-title":"Regul. Pept."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"13415","DOI":"10.1073\/pnas.96.23.13415","article-title":"Aminopeptidase A inhibitors as potential central antihypertensive agents","volume":"96","author":"Reaux","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"731","DOI":"10.3389\/fendo.2018.00731","article-title":"Thyroid Disorders Change the Pattern of Response of Angiotensinase Activities in the Hypothalamus-Pituitary-Adrenal Axis of Male Rats","volume":"9","author":"Segarra","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1530\/JOE-13-0417","article-title":"Hypooxytocinaemia in obese Zucker rats relates to oxytocin degradation in liver and adipose tissue","volume":"220","author":"Gajdosechova","year":"2014","journal-title":"J. Endocrinol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.lfs.2017.11.022","article-title":"Divergent profile between hypothalamic and plasmatic aminopeptidase activities in WKY and SHR. Influence of beta-adrenergic blockade","volume":"192","author":"Prieto","year":"2018","journal-title":"Life Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1055\/s-0031-1299693","article-title":"Angiotensinase and vasopressinase activities in hypothalamus, plasma, and kidney after inhibition of angiotensin-converting enzyme: Basis for a new working hypothesis","volume":"44","author":"Villarejo","year":"2012","journal-title":"Horm. Metab. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.lfs.2015.04.023","article-title":"Tissue distribution of CysAP activity and its relationship to blood pressure and water balance","volume":"134","author":"Prieto","year":"2015","journal-title":"Life Sci"},{"key":"ref_88","first-page":"197","article-title":"Cystinyl and pyroglutamyl-beta-naphthylamide hydrolyzing activities are modified coordinately between hypothalamus, liver and plasma depending on the thyroid status of adult male rats","volume":"69","author":"Segarra","year":"2018","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1093\/ajcp\/82.6.700","article-title":"Evaluation of Cytosolic Aminopeptidase in Human Sera: Evaluation in Hepatic Disorders","volume":"82","author":"Kanno","year":"1984","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"557","DOI":"10.3109\/1354750X.2012.701331","article-title":"Relationships of hepatic and pancreatic biomarkers with the cholestatic syndrome and tumor stage in pancreatic cancer","volume":"17","author":"Porta","year":"2012","journal-title":"Biomarkers"},{"key":"ref_91","first-page":"94","article-title":"Hypocaloric high-protein diet improves clinical and biochemical markers in patients with nonalcoholic fatty liver disease (NAFLD)","volume":"29","author":"Faintuch","year":"2014","journal-title":"Nutr. Hosp."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/00005344-199704000-00004","article-title":"Comparative Vasoconstrictor Effects of Angiotensin II, III, and IV in Human Isolated Saphenous Vein","volume":"29","author":"Li","year":"1997","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.3892\/etm.2014.1963","article-title":"Heparin modulation on hepatic nitric oxide synthase in experimental steatohepatitis","volume":"8","author":"Hassanin","year":"2014","journal-title":"Exp. Ther. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/3\/636\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:02:23Z","timestamp":1760173343000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/3\/636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,28]]},"references-count":93,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["nu12030636"],"URL":"https:\/\/doi.org\/10.3390\/nu12030636","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,28]]}}}