{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T19:12:42Z","timestamp":1768072362934,"version":"3.49.0"},"reference-count":91,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007064","name":"University of Ja\u00e9n","doi-asserted-by":"publisher","award":["ACCI\u00d3N 1 PAIUJA 2019 2020: BIO221."],"award-info":[{"award-number":["ACCI\u00d3N 1 PAIUJA 2019 2020: BIO221."]}],"id":[{"id":"10.13039\/501100007064","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>(1) Background: Prolonged feeding with a high-fat diet (HFD) acts as a stressor by activating the functions of the hypothalamic-pituitary-adrenal gland (HPA) stress axis, accompanied of hypertension by inducing the renin-angiotensin-aldosterone system. Angiotensinases enzymes are regulatory aminopeptidases of angiotensin metabolism, which together with the dipeptidyl peptidase IV (DPP-IV), pyroglutamyl- and tyrosyl-aminopeptidase (pGluAP, TyrAP), participate in cognitive, stress, metabolic and cardiovascular functions. These functions appear to be modulated by the type of fat used in the diet. (2) Methods: To analyze a possible coordinated response of aminopeptidases, their activities were simultaneously determined in the hypothalamus, adenohypophysis and adrenal gland of adult male rats fed diets enriched with monounsaturated (standard diet (S diet) supplemented with 20% virgin olive oil; VOO diet) or saturated fatty acids (diet S supplemented with 20% butter and 0.1% cholesterol; Bch diet). Aminopeptidase activities were measured by fluorimetry using 2-Naphthylamine as substrates. (3) Results: the hypothalamus did not show differences in any of the experimental diets. In the pituitary, the Bch diet stimulated the renin-angiotensin system (RAS) by increasing certain angiotensinase activities (alanyl-, arginyl- and cystinyl-aminopeptidase) with respect to the S and VOO diets. DPP-IV activity was increased with the Bch diet, and TyrAP activity decrease with the VOO diet, having both a crucial role on stress and eating behavior. In the adrenal gland, both HFDs showed an increase in angiotensinase aspartyl-aminopeptidase. The interrelation of angiotensinases activities in the tissues were depending on the type of diet. In addition, correlations were shown between angiotensinases and aminopeptidases that regulate stress and eating behavior. (4) Conclusions: Taken together, these results support that the source of fat in the diet affects several peptidases activities in the HPA axis, which could be related to alterations in RAS, stress and feeding behavior.<\/jats:p>","DOI":"10.3390\/nu13113939","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T22:25:54Z","timestamp":1636064754000},"page":"3939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Type of Fat in the Diet Influences Regulatory Aminopeptidases of the Renin-Angiotensin System and Stress in the Hypothalamic-Pituitary-Adrenal Axis in Adult Wistar Rats"],"prefix":"10.3390","volume":"13","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":[[2021,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3389\/fpsyt.2020.00443","article-title":"Pharmacological Treatment of Anxiety Disorders: The Role of the HPA Axis","volume":"11","author":"Tafet","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11360","DOI":"10.1038\/s41598-017-10815-y","article-title":"Dominance of the hypothalamus-pituitary-adrenal axis over the renin-angiotensin-aldosterone system is a risk factor for decreased insulin secretion","volume":"7","author":"Daimon","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.psyneuen.2018.12.003","article-title":"Maternal high fat diet programs hypothalamic-pituitary-adrenal function in adult rat offspring","volume":"102","author":"Niu","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1530\/JOE-12-0056","article-title":"The effects of high fat diet on the basal activity of the hypothalamus-pituitary-adrenal axis in mice","volume":"214","author":"Auvinen","year":"2012","journal-title":"J. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3892\/etm.2017.4498","article-title":"Hypothalamic-pituitary-adrenal axis hypersensitivity in female rats on a post-weaning high-fat diet after chronic mild stress","volume":"14","author":"Liu","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41387-019-0076-y","article-title":"Responsiveness of hypothalamo-pituitary-adrenal axis to leptin is impaired in diet-induced obese rats","volume":"9","author":"Shin","year":"2019","journal-title":"Nutr. Diabetes"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1038\/npp.2015.357","article-title":"High-Fat Diet Induced Anxiety and Anhedonia: Impact on Brain Homeostasis and Inflammation","volume":"41","author":"Dutheil","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35239","DOI":"10.1038\/srep35239","article-title":"The Effects of High-Fat-Diet Combined with Chronic Unpredictable Mild Stress on Depression-like Behavior and Leptin\/LepRb in Male Rats","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.bbr.2015.02.036","article-title":"Chronic high fat feeding increases anxiety-like behaviour and reduces transcript abundance of glucocorticoid signalling genes in the hippocampus of female rats","volume":"286","author":"Sivanathan","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1055\/s-0031-1291305","article-title":"Effects of high fat diet on the Basal activity of the hypothalamus-pituitary-adrenal axis in mice: A systematic review","volume":"43","author":"Auvinen","year":"2011","journal-title":"Horm. Metab. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/bs.vh.2018.10.002","article-title":"Inhibitors of Aldosterone Synthase","volume":"109","author":"Weldon","year":"2019","journal-title":"Vitam. Horm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/ajh\/hpw003","article-title":"The Role of Aldosterone in Obesity-Related Hypertension","volume":"29","author":"Kawarazaki","year":"2016","journal-title":"Am. J. Hypertens."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1161\/HYPERTENSIONAHA.118.12198","article-title":"Diet-Induced Obesity Promotes Kidney Endothelial Stiffening and Fibrosis Dependent on the Endothelial Mineralocorticoid Receptor","volume":"73","author":"Aroor","year":"2019","journal-title":"Hypertension"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1530\/JOE-18-0026","article-title":"Impact of MR on Mature Adipocytes in High-Fat\/High-Sucrose Diet-Induced Obesity","volume":"239","author":"Hayakawa","year":"2018","journal-title":"J. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1096\/fj.08-111914","article-title":"Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet","volume":"22","author":"Michailidou","year":"2008","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3317\/jraas.2006.003","article-title":"Role of angiotensin II in cardiovascular disease therapeutic implications of more than a century of research","volume":"7","author":"Ferrario","year":"2006","journal-title":"J. Renin Angiotensin Aldosterone Syst."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"848","DOI":"10.3389\/fphys.2018.00848","article-title":"Renal and Blood Pressure Response to a High-Salt Diet in Mice with Reduced Global Expression of the Glucocorticoid Receptor","volume":"9","author":"Ivy","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_18","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_19","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_20","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1210\/jc.2015-3568","article-title":"Association Between Pituitary-Adrenal Axis Dominance Over the Renin-Angiotensin-Aldosterone System and Hypertension","volume":"101","author":"Daimon","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22082","DOI":"10.1038\/s41598-020-79096-2","article-title":"Chronically infused angiotensin II induces depressive-like behavior via microglia activation","volume":"10","author":"Park","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez-V\u00edas, G., Segarra, A.B., Ram\u00edrez-S\u00e1nchez, M., and Prieto, I. (2021). Effects of Virgin Olive Oil on Blood Pressure and Renal Aminopeptidase Activities in Male Wistar Rats. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105388"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez-V\u00edas, G., Segarra, A.B., Ram\u00edrez-S\u00e1nchez, M., and Prieto, I. (2020). The Role of High Fat Diets and Liver Peptidase Activity in the Development of Obesity and Insulin Resistance in Wistar Rats. Nutrients, 12.","DOI":"10.3390\/nu12030636"},{"key":"ref_24","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_25","doi-asserted-by":"crossref","unstructured":"Segarra, A.B., Dom\u00ednguez-V\u00edas, G., Redondo, J., Mart\u00ednez-Ca\u00f1amero, M., Ram\u00edrez-S\u00e1nchez, M., and Prieto, I. (2021). Hypothalamic Renin\u2013Angiotensin System and Lipid Metabolism: Effects of Virgin Olive Oil versus Butter in the Diet. Nutrients, 13.","DOI":"10.3390\/nu13020480"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1080\/07420528.2017.1354871","article-title":"Diurnal opposite variation between angiotensinase activities in photo-neuro-endocrine tissues of rats","volume":"34","author":"Prieto","year":"2017","journal-title":"Chronobiol. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"H437","DOI":"10.1152\/ajpheart.00485.2016","article-title":"High aminopeptidase A activity contributes to blood pressure control in ob\/ob mice by AT2 receptor-dependent mechanism","volume":"312","author":"Morais","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fmolb.2020.00094","article-title":"The Type of Fat in the Diet Influences the Behavior and the Relationship Between Cystinyl and Alanyl Aminopeptidase Activities in Frontal Cortex, Liver, and Plasma","volume":"7","author":"Segarra","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_29","first-page":"1852","article-title":"Angiotensin-II mediates norepinephrine and neuropeptide-Y secretion in a human pheochromocytoma","volume":"79","author":"Grouzmann","year":"1994","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/B978-0-12-411512-5.00006-3","article-title":"Interactions of neuropeptide y, catecholamines, and angiotensin at the vascular neuroeffector junction","volume":"68","author":"Westfall","year":"2013","journal-title":"Adv. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"H2188","DOI":"10.1152\/ajpheart.00384.2008","article-title":"Nerve stimulation induced overflow of neuropeptide Y and modulation by angiotensin II in spontaneously hypertensive rats","volume":"295","author":"Byku","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1055\/s-2007-978900","article-title":"Neuropeptide-Y family of peptides in the autocrine-paracrine regulation of adrenocortical function","volume":"30","author":"Nussdorfer","year":"1998","journal-title":"Horm. Metab. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1365-2826.1995.tb00663.x","article-title":"Role of neuropeptide Y in the regulation of tyrosine hydroxylase messenger ribonucleic acid levels in the male rat arcuate nucleus as evaluated by in situ hybridization","volume":"7","author":"Hong","year":"1995","journal-title":"J. Neuroendocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1159\/000126816","article-title":"Role of Neuropeptide Y in the Regulation of Tyrosine Hydroxylase Gene Expression in Rat Adrenal Glands","volume":"61","author":"Hong","year":"1995","journal-title":"Neuroendocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0196-9781(01)00353-9","article-title":"Neuropeptide Y and the Adrenal Gland: A Review","volume":"22","author":"Renshaw","year":"2001","journal-title":"Peptides"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.yhbeh.2015.04.008","article-title":"Maternal high-fat diet programming of the neuroendocrine system and behavior","volume":"76","author":"Sullivan","year":"2015","journal-title":"Horm. Behav."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.psyneuen.2017.06.002","article-title":"Saturated high-fat feeding independent of obesity alters hypothalamus-pituitary-adrenal axis function but not anxiety-like behaviour","volume":"83","author":"Hryhorczuk","year":"2017","journal-title":"Psychoneuroendocrinology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/jne.12155","article-title":"Neuropeptide Y and leptin sensitivity is dependent on diet composition","volume":"26","author":"Eggels","year":"2014","journal-title":"J. Neuroendocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.bbr.2018.08.029","article-title":"Role of hypothalamus-pituitary-adrenal axis modulation in the stress-resilient phenotype of DPP4-deficient rats","volume":"356","author":"Golub","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.psyneuen.2015.01.007","article-title":"DPP4-Deficient Congenic Rats Display Blunted Stress, Improved Fear Extinction and Increased Central NPY","volume":"53","author":"Canneva","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13098-017-0226-0","article-title":"Dipeptidyl peptidase-4 levels are increased and partially related to body fat distribution in patients with familial partial lipodystrophy type 2","volume":"9","author":"Valerio","year":"2017","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez-V\u00edas, G., Segarra, A.B., Ram\u00edrez-S\u00e1nchez, M., and Prieto, I. (2021). High-Fat Diets Modify the Proteolytic Activities of Dipeptidyl-Peptidase IV and the Regulatory Enzymes of the Renin\u2013Angiotensin System in Cardiovascular Tissues of Adult Wistar Rats. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091149"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Durillo, F.T., Segarra, A.B., Villarejo, A.B., 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_44","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.npep.2016.02.007","article-title":"Identifying neuropeptide Y (NPY) as the main stress-related substrate of dipeptidyl peptidase 4 (DPP4) in blood circulation","volume":"57","author":"Wagner","year":"2016","journal-title":"Neuropeptides"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0006-8993(86)90845-0","article-title":"Metabolism of thyrotropin-releasing hormone in human cerebrospinal fluid. Isolation and characterization of pyroglutamate aminopeptidase activity","volume":"364","author":"Prasad","year":"1986","journal-title":"Brain Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1159\/000125075","article-title":"Modulation of plasma glucose levels by thyrotropin-releasing hormone administered intracerebroventricularly in the rat","volume":"48","author":"Marubashi","year":"1988","journal-title":"Neuroendocrinology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1016\/0024-3205(87)90667-9","article-title":"Thyrotropin-releasing hormone and cyclo (His-Pro)-like immunoreactivities in the cerebrospinal fluids of \u2018normal\u2019 infants and adults, and patients with various neuropsychiatric and neurologic disorders","volume":"41","author":"Iriuchijima","year":"1987","journal-title":"Life Sci."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3109\/00207459309003324","article-title":"Effect of swimming-to-exhaustion stress on the Tyr-aminopeptidase activity in different brain areas of the rat","volume":"69","author":"Irazusta","year":"1993","journal-title":"Int. J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1007\/s11064-007-9356-3","article-title":"Brain-specific aminopeptidase: From enkephalinase to protector against neurodegeneration","volume":"32","author":"Hui","year":"2007","journal-title":"Neurochem. Res."},{"key":"ref_51","first-page":"816","article-title":"Effect of lithium treatments on the tyrosine-aminopeptidase activities in the rat brain and the pituitary gland","volume":"49","author":"Astiazaran","year":"1999","journal-title":"Arzneimittelforschung"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1055\/s-2003-41302","article-title":"Angiotensinase activity in hypothalamus and pituitary of hypothyroid, euthyroid and hyperthyroid adult male rats","volume":"35","author":"Prieto","year":"2003","journal-title":"Horm. Metab. Res."},{"key":"ref_53","unstructured":"Paxinos, G., and Watson, C. (2007). The Rat Brain in Stereotaxic Coordinates, Academic Press. [6th ed.]."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/0006-291X(62)90029-3","article-title":"Fluorometric Measurement of Alkaline Phosphatase and Aminopeptidase Activities in the Order of 10-14 Mole","volume":"9","author":"Greenberg","year":"1962","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/0005-2744(71)90098-2","article-title":"A soluble aspartate aminopeptidase from dog kidney","volume":"242","author":"Cheung","year":"1971","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/0005-2744(80)90100-X","article-title":"Purification by affinity chromatography using amastatin and properties of aminopeptidase A from pig kidney","volume":"613","author":"Tobe","year":"1980","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1055\/s-2001-17207","article-title":"Effect of valsartan on angiotensin II- and vasopressin-degrading activities in the kidney of normotensive and hypertensive rats","volume":"33","author":"Prieto","year":"2001","journal-title":"Horm. Metab. Res."},{"key":"ref_58","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_59","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/0006-291X(91)91057-J","article-title":"Structural and immunological evidence for the identity of prolyl aminopeptidase with leucyl aminopeptidase","volume":"178","author":"Matsushima","year":"1991","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1432-1033.1990.tb15603.x","article-title":"Prolyl aminopeptidase from rat brain and kidney. Action on peptides and identification as leucyl aminopeptidase","volume":"190","author":"Turzynski","year":"1990","journal-title":"Eur. J. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1053\/meta.2002.28967","article-title":"Effect of acute and chronic alcohol treatment and their superimposition on lysosomal, cytoplasmic, and proteosomal protease activities in rat skeletal muscle in vivo","volume":"51","author":"Koll","year":"2002","journal-title":"Metabolism"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/0378-4347(91)80286-L","article-title":"Use of L-prolyl-L-leucylglycinamide (MIF-1) for the high-performance liquid chromatographic determination of proline iminopeptidase activity in rat liver","volume":"563","author":"Hiraoka","year":"1991","journal-title":"J. Chromatogr."},{"key":"ref_63","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_64","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2478\/enr-2019-0007","article-title":"Enkephalinase activity is modified and correlates with fatty acids in frontal cortex depending on fish, olive or coconut oil used in the diet","volume":"53","author":"Segarra","year":"2019","journal-title":"Endocr. Regul."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.psyneuen.2014.12.002","article-title":"High fat feeding is associated with stimulation of the hypothalamic-pituitary-adrenal axis and reduced anxiety in the rat","volume":"52","author":"McNeilly","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e1248","DOI":"10.4088\/JCP.15m10154","article-title":"Increased Dipeptidyl Peptidase-4 Activity Is Associated with High Prevalence of Depression in Middle-Aged and Older Adults: A Cross-Sectional Study","volume":"77","author":"Zheng","year":"2016","journal-title":"J. Clin. Psychiatry"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.2337\/dc16-0316","article-title":"Association of Plasma DPP4 Activity with Mild Cognitive Impairment in Elderly Patients with Type 2 Diabetes: Results from the GDMD Study in China","volume":"39","author":"Zheng","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.bbr.2010.09.024","article-title":"Dipeptidyl peptidase IV (DPP4)-deficiency attenuates diet-induced obesity in rats: Possible implications for the hypothalamic neuropeptidergic system","volume":"216","author":"Stephan","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0278-5846(94)00101-M","article-title":"Evidence for an immune response in major depression: A review and hypothesis","volume":"19","author":"Maes","year":"1995","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/ijo.2016.183","article-title":"High fat induces acute and chronic inflammation in the hypothalamus: Effect of high-fat diet, palmitate and TNF-\u03b1 on appetite-regulating NPY neurons","volume":"41","author":"Dalvi","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1080\/1028415X.2018.1465713","article-title":"High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome","volume":"22","author":"Hassan","year":"2019","journal-title":"Nutr. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0167-0115(02)00253-7","article-title":"Angiotensin II Mediates Catecholamine and Neuropeptide Y Secretion in Human Adrenal Chromaffin Cells through the AT1 Receptor","volume":"111","author":"Cavadas","year":"2003","journal-title":"Regul. Pept."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/hr.2009.129","article-title":"Effect of high-fat diet feeding on hypothalamic redox signaling and central blood pressure regulation","volume":"32","author":"Erdos","year":"2009","journal-title":"Hypertens. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1161\/01.HYP.37.2.365","article-title":"Antisense inhibition of thyrotropin-releasing hormone reduces arterial blood pressure in spontaneously hypertensive rats","volume":"37","author":"Alvarez","year":"2001","journal-title":"Hypertension"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1530\/eje.0.1480089","article-title":"Nitric oxide decreases the production of inositol phosphates stimulated by angiotensin II and thyrotropin-releasing hormone in anterior pituitary cells","volume":"148","author":"Velardez","year":"2003","journal-title":"Eur. J. Endocrinol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1152\/ajpendo.2001.280.3.E462","article-title":"Desensitization of angiotensin II: Effect on [Ca2+]i, inositol triphosphate, and prolactin in pituitary cells","volume":"280","author":"Iglesias","year":"2001","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_77","first-page":"E553","article-title":"Role of calcium in dopaminergic regulation of TRH- and angiotensin II-stimulated prolactin release","volume":"260","author":"Login","year":"1991","journal-title":"Am. J. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/BF00965728","article-title":"Developmental Changes in the Distribution of Rat Brain Pyroglutamate Aminopeptidase, a Possible Determinant of Endogenous Cyclo(His-Pro) Concentrations","volume":"8","author":"Prasad","year":"1983","journal-title":"Neurochem. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0149-7634(88)80069-1","article-title":"Cyclo(His-Pro): Its distribution, origin and function in the human","volume":"12","author":"Prasad","year":"1988","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"805","DOI":"10.2174\/1389203719666180430155112","article-title":"Potential Influence of Cyclo(His-Pro) on Proteostasis: Impact on Neurodegenerative Diseases","volume":"19","author":"Grottelli","year":"2018","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/BF00223538","article-title":"Histidyl-proline diketopiperazine: Its biological role as a regulatory peptide","volume":"42","author":"Peterkofsky","year":"1982","journal-title":"Mol. Cell. Biochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.neuint.2006.09.009","article-title":"The expression of TRH, its receptors and degrading enzyme is differentially modulated in the rat limbic system during training in the Morris water maze","volume":"50","year":"2007","journal-title":"Neurochem. Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1210\/endo.132.3.7679984","article-title":"Intraventricular administration of histidyl-proline-diketopiperazine [Cyclo(His-Pro)] suppresses prolactin secretion and synthesis: A possible role of Cyclo(His-Pro) as dopamine uptake blocker in rat hypothalamus","volume":"132","author":"Jikihara","year":"1993","journal-title":"Endocrinology"},{"key":"ref_84","first-page":"1226","article-title":"Effect of TRH and histidyl-proline diketopiperazine (cyclo(His-Pro)) on catecholamine secretion","volume":"65","author":"Miyamori","year":"1989","journal-title":"Nihon Naibunpi Gakkai Zasshi"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Grottelli, S., Ferrari, I., Pietrini, G., Peirce, M.J., Minelli, A., and Bellezza, I. (2016). The Role of Cyclo(His-Pro) in Neurodegeneration. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17081332"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.mcn.2018.11.002","article-title":"Cyclo(His-Pro) inhibits NLRP3 inflammasome cascade in ALS microglial cells","volume":"94","author":"Grottelli","year":"2019","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.neuroscience.2016.10.035","article-title":"Zinc plus cyclo-(His-Pro) promotes hippocampal neurogenesis in rats","volume":"339","author":"Choi","year":"2016","journal-title":"Neuroscience"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bbacli.2016.09.003","article-title":"Metabolic relationship between diabetes and Alzheimer\u2019s Disease affected by Cyclo(His-Pro) plus zinc treatment","volume":"7","author":"Song","year":"2016","journal-title":"BBA Clin."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0196-9781(83)90172-9","article-title":"Specific binding to adrenal particulate fraction of cyclo(histidyl-proline), a TRH metabolite","volume":"4","author":"Bataini","year":"1983","journal-title":"Peptides"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"104831","DOI":"10.1016\/j.psyneuen.2020.104831","article-title":"Are the thyroid and adrenal system alterations linked in depression?","volume":"122","author":"Mokrani","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"533872","DOI":"10.3389\/fpsyt.2020.533872","article-title":"Dopaminergic, Noradrenergic, Adrenal, and Thyroid Abnormalities in Psychotic and Affective Disorders","volume":"11","author":"Duval","year":"2020","journal-title":"Front. Psychiatry"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/3939\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:25:38Z","timestamp":1760167538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/3939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,4]]},"references-count":91,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["nu13113939"],"URL":"https:\/\/doi.org\/10.3390\/nu13113939","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,4]]}}}