The Role of High Fat Diets and Liver Peptidase Activity in the Development of Obesity and Insulin Resistance in Wistar Rats

Abstract

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 β-cell usefulness (% β-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.Nutrients 2020, 12, 636 2 of 17 the past few decades, and it typically it is a part of a cluster of metabolic syndrome conditions that increase the chance of developing several related disorders, such as type 2 diabetes, dyslipidemia, abnormal cholesterol levels, hypertension, stroke, heart disease, and cancer [2,3]. Several studies have documented a positive relationship between a high-fat diet (HFD) intake and obesity [4]. The efficacy of the current strategies of treatment for diseases that are caused by obesity is still not entirely satisfactory, and new approaches must be considered. Several studies ha...

Hypothalamic Renin–Angiotensin System and Lipid Metabolism: Effects of Virgin Olive Oil versus Butter in the Diet

“…Our results indicated that only the animals fed the diet enriched with saturated fat (butter) showed significantly higher values of body weight and adiposity (total visceral fat) compared to control and EVOO diets, although the EVOO diet contained the same energy density, and that no marked differences were recorded in food intake although a significant reduction in food intake was established in the butter diet at the end of the experimental period, probably as a response to the increase in body weight. This beneficial effect of olive oil in the regulation of body weight has been described in previous works [ 19 , 20 , 21 , 22 ] and could be related to the minor components included in the unsaponifiable fraction of EVOO [ 23 ] and gut dysbiosis [ 24 , 25 ].…”

Effects of Virgin Olive Oil on Blood Pressure and Renal Aminopeptidase Activities in Male Wistar Rats

“…High-fat diets (HFDs) are related to factors that condition the metabolic syndrome, such as the development of obesity and various pathologies such as hypertension, heart disease, stroke, atherosclerosis, diabetes, dyslipidemia, cancer and infertility [1][2][3][4][5]. Hypertension is the most prevalent factor in overweight people as a result of several mechanisms including hyperinsulinemia, insulin resistance, and increased sympathetic activity [6,7].…”

“…Different local RASs could be affected by changes in the degree of saturation of fat consumed in the diet. Within these local systems, angiotensin peptides are metabolized by various enzymes of the aminopeptidase (AP) family, also called angiotensinases, and previous results of our research group have shown that the activities of these peptidases are affected by the type of fatty acids consumed with the diet [5,14,25,26]. These APs are relevant in the control of blood pressure (BP) and renal function, participating in the regulation of the systemic and local RAS, but also like predictive renal injury biomarkers on the luminal surface of the renal tubule [27,28].…”

“…Among them, aspartyl-AP activities (AspAP; EC 3.4.11.21), responsible for the metabolism of Ang I to Ang 2-10; glutamyl-AP (GluAP or aminopeptidase A, APA; EC 3.4.11.7), metabolizes Ang II into Ang III; alanyl-AP (AlaAP or aminopeptidase M, APM; EC 3.4.11.2) and/or arginyl-AP (ArgAP or aminopeptidase B, APB; EC 3.4.11.6), responsible for the metabolism of Ang III to Ang IV and Ang 4-8; insulin-regulated AP (IRAP; 3.4.11.3), also called placental AP-leucyl (LAP), cystinyl-AP (CysAP), oxytokinase or vasopressinase, which as mentioned above, was identified as the binding site for the AT4 receptor Ang IV [29][30][31][32]. It has been suggested that the metabolizing activity of Ang II (GluAP) may be influenced by the composition of fatty acids in the diet and by the cholesterol content [5,14,15,33] directly or indirectly, and with an important role in the development of cardiovascular and kidney disorders.…”

Beneficial Effects of Algerian Green Alga Ulva lactuca and Its Hydroethanolic Extract on Insulin Resistance and Cholesterol Reverse Transport in High-Fat/Streptozotocin Diabetic Rats

“…In a previous study, Lichtenstein and Schwab (2000) showed that a HFD containing high amount of saturated fatty acids decreases insulin sensitivity and, consequently, affects glucose homeostasis. This could involve inactivation of GLP-1, an incretin hormone with antidiabetic effects, by dipeptidyl peptidase-IV ( Tahara et al, 2009 ; Domínguez-Vías et al, 2020 ). Consumption of the HFD supplemented with whole alga or its extract increased serum insulin concentrations and HOMA-β indexes compared with the HFD.…”