Abstract

(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.

Highlights

  • The rats were randomly separated by dietary groups: (1) a control group, called the standard diet, which corresponded to a commercial feed for laboratory rodents (Panlab, Barcelona, Spain), with a composition nutritional consisting of proteins (16.5%), total fat (3%), carbohydrates (60%, nitrogen-free extract (NFE)), minerals (5%) and fiber (4%). (2) The other two groups corresponded to high-fat diets (HFD), based on diet S but supplemented with a predominantly high composition in monounsaturated fatty acid (MUFA) (20% virgin olive oil; VOO diet, n = 5) or saturated fatty acid (SAFA) (20% butter + 0.1% cholesterol; diet Bch, n = 5) to simulate the average cholesterol content of the western diet

  • (sol/mb), ArgAP, Cystinyl-aminopeptidase activity aminopeptidase activity (CysAP), in relation to the S and VOO diets. This central mechanism would explain in our experiments the increase in systolic blood pressure (BP) (SBP) together with the changes in the angiotensinase activities of the kidney that we recently described, being the GluAP and CysAP activities of the renal medulla very high with the

  • The greatest involvement of angiotensinase activities occurs in the pituitary, showing an activation of the renin-angiotensin system (RAS) pathway with the Bch diet; the VOO diet seems to go against the results with the Bch diet, presenting significantly lower values

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Summary

Introduction

HFDs influence the classical main components of the local and central RAS, as well as the behavior of other non-classical RAS elements such as Ang 2–10, Ang-III, Ang-IV These metabolites are regulated by angiotensinase enzymes (Figure 1), among them we find the activities: aspartyl-AP (AspAP; EC 3.4.11.21), hydrolyzes Ang-I to form Ang 2–10; glutamyl-AP (GluAP or AP-A; EC 3.4.11.7), hydrolyzes Ang-II to form Ang-III; alanyl-AP (AlaAP or AP-M; EC 3.4.11.2). Angiotensinases are known to be closely related to cognitive, metabolic and cardiovascular functions, but the type of fat in the diet can influence angiotensinases and, behavior [28]. Several studies consider that a diet high in saturated fat, regardless of obesity, alters the function of the HPA axis and contributes in different ways to behavior, stress and anxiety [36,37].

2-10: Angiotensin
Animals and Diets
Assay of Aminopeptidase Activities
Protein Measurement
Statistic Analysis
Results
Angiotensinase Activities
Aspartyl-Aminopeptidase Activity
Alanyl-Aminopeptidase and Arginyl-Aminopeptidase Activities
Cystinyl-Aminopeptidase Activity
Conclusions

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