apelin-13-peptide and Body-Weight

Dobutamine is the currently recommended β-adrenergic inotropic drug for supporting sepsis-induced myocardial dysfunction when cardiac output index remains low after preload correction. Better and safer therapies are nonetheless mandatory because responsiveness to dobutamine is limited with numerous side effects. Apelin-13 is a powerful inotropic candidate that could be considered as an alternative noncatecholaminergic support in the setting of inflammatory cardiovascular dysfunction.. Interventional controlled experimental animal study.. Tertiary care university-based research institute.. One hundred ninety-eight adult male rats.. Using a rat model of "systemic inflammation-induced cardiac dysfunction" induced by intraperitoneal lipopolysaccharide injection (10 mg/kg), hemodynamic efficacy, cardioprotection, and biomechanics were assessed under IV osmotic pump infusions of apelin-13 (0.25 μg/kg/min) or dobutamine (7.5 μg/kg/min).. In this model and in both in vivo and ex vivo studies, apelin-13 compared with dobutamine provoked distinctive effects on cardiac function: 1) optimized cardiac energy-dependent workload with improved cardiac index and lower vascular resistance, 2) upgraded hearts' apelinergic responsiveness, and 3) consecutive downstream advantages, including increased urine output, enhanced plasma volume, reduced weight loss, and substantially improved overall outcomes. In vitro studies confirmed that these apelin-13-driven processes encompassed a significant and rapid reduction in systemic cytokine release with dampening of myocardial inflammation, injury, and apoptosis and resolution of associated molecular pathways.. In this inflammatory cardiovascular dysfunction, apelin-13 infusion delivers distinct and optimized hemodynamic support (including positive fluid balance), along with cardioprotective effects, modulation of circulatory inflammation and extended survival.

Topics: Animals; Body Weight; Cardiac Output; Cardiomyopathies; Cardiotonic Agents; Cytokines; Disease Models, Animal; Dobutamine; Intercellular Signaling Peptides and Proteins; Lipopolysaccharides; Male; Mitogen-Activated Protein Kinases; Myocardium; Nitric Oxide Synthase Type II; Peroxidase; Phosphorylation; Plasma Volume; Rats; Survival Rate; Vascular Resistance; Water-Electrolyte Balance

Apelin is a recently discovered peptide produced by several tissues in the various vertebrates and fish. Apelin has been suggested to have role in regulation of many diverse physiological functions including food intake, energy homoeostasis, immunity, osmoregulation and reproduction. In this study, apelin-13 levels in the blood serum of Cyprinus carpio and Capoetta trutta were determined. Then the results were compared between two species and sexes of each species. Apelin-13 level was analysed using the enzyme-linked immunoassay (ELISA) kit (Rat apelin-13 ELISA kit, catalog no: CSB-E14367r). Apelin-13 level in the blood serum of C. trutta was significantly higher than those of the C. carpio (p < 0.05). However, its levels were observed to be no significant difference (p > 0.05) that compared to between sexes of each species. There was a significant negative correlation (r = -0.829, p = 0.0001) between the apelin-13 level and body weight of C. carpio. However, no significant correlation (r = -0.022, p = 0.924) between the apelin-13 level and weight of C. trutta observed.

Topics: Animals; Body Weight; Cyprinidae; Female; Gene Expression Regulation; Intercellular Signaling Peptides and Proteins; Male; Sex Characteristics; Species Specificity

Apelin is the endogenous ligand of APJ, which belongs to the family of G protein‑coupled receptors. Apelin and APJ are highly expressed in various cardiovascular tissues, including the heart, kidney and vascular endothelial and smooth muscle cells. Although apelin exerts hypotensive effects via activation of endothelial nitric oxide synthase (eNOS), the ability of apelin to regulate blood pressure under pathological conditions is poorly understood. In the current study, NG‑nitro‑L‑arginine methyl ester (L‑NAME), a potent NOS inhibitor, was administered chronically, to induce peripheral vascular damage in mice. L‑NAME‑treated mice exhibited hypertension, increased vascular cell adhesion molecule‑1 and plasminogen activator inhibitor‑1 mRNA levels in the aorta and impaired vasodilatation associated with decreased aortic eNOS expression, consistent with endothelial damage. Three days following withdrawal of L‑NAME treatment, the blood pressure response to apelin stimulation was assessed. Although apelin reduced blood pressure in non‑treated mice, it was found to transiently elevate blood pressure in L‑NAME‑treated mice. These results indicate that apelin functions as a vasopressor peptide under pathological conditions, including vascular endothelial dysfunction in mice.

Topics: Animals; Aorta; Blood Pressure; Body Weight; Endothelium, Vascular; Gene Expression Regulation; Hypertension; Intercellular Signaling Peptides and Proteins; Mice; Mice, Inbred ICR; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type III; Systole; Vasoconstrictor Agents; Vasodilation

The central administration of apelin, a recently identified adipokine, has been shown to affect food and water intake. The present study investigated whether body weight could affect an animal's response to apelin. The effects of centrally-administered apelin-13 on food and water intake, activity and metabolic rate were investigated in adult male diet-induced obese (DIO) rats fed either a high fat (32%) or control diet. Rats were administered i.c.v. apelin-13, 15-30 min prior to lights out, and food and water intake, activity and metabolic rate were assessed. Intracerebroventricular administration of apelin-13 decreased food and water intake and respiratory exchange ratio in DIO rats on the control diet, but had no effect in DIO rats on the high-fat diet. In an effort to identify potential central mechanisms explaining the observed physiological responses, the mRNA level of the apelin receptor, APJ, was examined in the hypothalamus. A high-fat diet induced an up-regulation of the expression of the receptor. Apelin induced a down-regulation of the receptor, but only in the DIO animals on the high-fat diet. In conclusion, we have demonstrated a diminished central nervous system response to apelin that is coincident with obesity.

Topics: Animals; Apelin Receptors; Body Weight; Cytokines; Diet; Dietary Fats; Drinking; Eating; Energy Metabolism; Hypothalamus; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Obesity; Plasminogen Activator Inhibitor 1; Rats; Receptors, G-Protein-Coupled

The peptide apelin has been located in a wide range of tissues, including the gastrointestinal tract, stomach and adipose tissue. Apelin and its receptor has also been detected in the arcuate and paraventricular nuclei of the hypothalamus, which are involved in the control of feeding behaviour and energy expenditure. This distribution suggests apelin may play a role in energy homeostasis, but previous attempts to discern the effects of apelin by acute injection into the brain have yielded conflicting results. We examined the effect of a chronic 10-day intracerebroventricular (i.c.v.) infusion of apelin-13 into the third ventricle on food intake, body temperature and locomotor activity in C57BL/6 mice. Apelin-13 (1 microg/day) increased food intake significantly on days 3-7 of infusion; thereafter, food intake of treated and control individuals converged. This convergence was potentially because of progressive conversion of apelin-13 to [Pyr(1)]apelin-13 which has a four-fold lower receptor binding affinity at the orphan G protein-coupled receptor, APJ. Locomotor activity was also higher in the apelin-treated mice, especially during the nocturnal peak, when most feeding occurs, and the first hours of the light phase. Body temperature was also elevated during this increased period of activity, but was otherwise unaffected. Apelin-13-infused animals gained more weight than the saline-infused controls, suggesting the elevated locomotor activity did not offset the increased food intake. Elevated locomotion and the consequent increases in body temperature were probably secondary effects to the increased food intake. These results suggest that apelin-13 may play a central role in the control of feeding behaviour and is one of only two peripheral ligands known to stimulate rather than inhibit intake. As apelin production is elevated during obesity, this may provide an important feed-forward mechanism exacerbating the problem. Antagonists of the apelin receptor may therefore be useful pharmaceuticals in the treatment of obesity.

Topics: Animals; Body Temperature; Body Weight; Drug Administration Schedule; Drug Stability; Eating; Feeding Behavior; Female; Injections, Intraventricular; Intercellular Signaling Peptides and Proteins; Mice; Mice, Inbred C57BL; Motor Activity; Photoperiod; Time Factors

Apelin, the endogenous ligand of the APJ receptor, has been identified in a variety of tissues, including stomach, heart, skeletal muscle, and white adipose tissue. We sought to clarify the effects of apelin on body adiposity and the expression of uncoupling proteins (UCPs) in C57BL/6 mice. Treatment with ip apelin at a dose of 0.1 mumol/kg.d for 14 d decreased the weight of white adipose tissue and serum levels of insulin and triglycerides, compared with controls, without influencing food intake. Apelin treatment also decreased body adiposity and serum levels of insulin and triglycerides in obese mice fed a high-fat diet. Apelin increased the serum adiponectin level and decreased that of leptin. Additionally, apelin treatment increased mRNA expression of UCP1, a marker of peripheral energy expenditure, in brown adipose tissue (BAT) and of UCP3, a regulator of fatty acid export, in skeletal muscle. In addition, immunoblot bands and relative densities of UCP1 content in BAT were also higher in the apelin group than controls. Furthermore, apelin treatment increased body temperature and O(2) consumption and decreased the respiratory quotient. In conclusion, apelin appears to regulate adiposity and lipid metabolism in both lean and obese mice. In addition, apelin regulates insulin resistance by influencing the circulating adiponectin level, the expression of BAT UCP1, and energy expenditure in mice.

Topics: Adiponectin; Adipose Tissue, White; Adiposity; Animals; Body Weight; Dose-Response Relationship, Drug; Eating; Gene Expression Regulation; Glucose Tolerance Test; Intercellular Signaling Peptides and Proteins; Ion Channels; Leptin; Mice; Mice, Inbred C57BL; Mitochondrial Proteins; Organ Size; RNA, Messenger; Time Factors; Triglycerides; Uncoupling Protein 1; Uncoupling Protein 2; Uncoupling Protein 3