Decreased Plasma Octanoylated Ghrelin Levels in Mice by Oleanolic Acid

Abstract

INTRODUCTION Ghrelin is a 28-amino-acid peptide hormone initially identified in the rat stomach that acts as an endogenous ligand for the growth hormone secretagogue receptor 1. Ghrelin circulates in the blood as two main isoforms: octanoylated ghrelin and des-acyl ghrelin 2. Octanoylated ghrelin, the active form, stimulates appetite and induces body weight gain, whereas des-acyl ghrelin, which has no acyl modification, does not have these activities 3. Furthermore, octanoylated ghrelin decreases energy expenditure by decreasing oxygen consumption and suppressing thermogenesis in brown adipose tissue 4 6. Therefore, lowering plasma octanoylated ghrelin levels may be an important strategy for the prevention and treatment of obesity. The conversion of the proghrelin precursor to octanoylated ghrelin involves two steps, i.e., octanoylation at the serine-3 residue, which is catalyzed by ghrelin O-acyl transferase GOAT 7 9 , and cleavage by prohormone convertases PC , such as furin, PC1/3, or PC2 10, 11. In ghrelin octanoylation, octanoyl-CoA is a substrate for GOAT. Oc

Oleanolic Acid: Extraction, Characterization and Biological Activity

“…Similarly, Gamede et al [ 96 ] have shown that OA significantly decreased body weight, TG, and LDL in plasma of prediabetic rats and significant rise of HDL. Further, OA administration lowers saturated FFA and increases mono/polyunsaturated FFA in neonatal rats fed with an HF diet [ 97 ], and significantly diminishes the plasma levels of octanoylated ghrelin and the body weight gain in comparison to non-OA-fed rats [ 98 ]. In the liver of spontaneously hypertensive rats (SHR) treated with OA (1.08 mg/kg) for 4 weeks, Zhang et al [ 99 ] observed a decrease in TG levels; however, they also found increased plasma LDL-C levels, with no significant effects on HDL-C and total cholesterol.…”

Oleanolic Acid Improves Obesity-Related Inflammation and Insulin Resistance by Regulating Macrophages Activation

“…Then the obese mice were intragastric administrated with vehicle, 25 mg/kg or 50 mg/kg OA for 4 weeks. The tested OA concentration was adapted from previous studies that used doses of 20, 40, 250 mg/kg/day, or 50 mg/kg/3 days in mice (Wang et al, 2015;Su et al, 2018;Nakajima et al, 2019), and 5-100 mg/kg/day in rats (Ying et al, 2014;Lee et al, 2016;Matumba et al, 2019).…”

Potential Protective Effect of Oleanolic Acid on the Components of Metabolic Syndrome: A Systematic Review

“…In this line, the literature supports that OA increases insulin biosynthesis and secretion [10], which is in accordance with the increased insulin levels and HOMA-β index [37], as well as the reduced FSI levels [35,36,38,43]. In addition, Li et al [33], Wang et al [35], Su et al [37], and Nyakudya et al [40] reported an improvement in the HOMA-IR index, whereas Gamede et al [41] reported an improvement of the HOMA-2 IR index. These findings might be explained by the availability of OA to modulate insulin signaling pathways such as glycogen synthase (GS)/glycogen phosphorylase (GP) signaling pathway [61,62] or the insulin receptor substrate 1 (IRS1)-glucose transporter 4 (GLUT4) pathway via NF-κB [17].…”

“…Molepo et al [12] administered OA to neonatal rats fed with a HF diet and observed a decrease of saturated FFA, and an increase of mono/polyunsaturated FFA. OA administration by Nakajima et al [41] significantly reduced the plasma levels of octanoylated ghrelin levels and the body weight gain in comparison to non-OA-fed rats.…”

“…This result of OA in leptin serum levels might be due to an impairing leptin signaling in hyperlipidemic conditions [58]. Although the mechanism by which OA reduces body weight is not yet clear, two of the studies that reported a decrease in body weight also observed a reduction of ghrelin levels (Gamede et al [39] and Nakajima et al [41]). Ghrelin has been shown to induce body weight gain through increasing food intake [59].…”