Hyperleptinemia results in systemic inflammation and the exacerbation of ischemia-reperfusion myocardial injury

Abstract

Aim Hyperleptinemia potentiates the effects of many atherogenic factors, such as inflammation, platelet aggregation, migration, hypertrophy, proliferation of vascular smooth muscle cells, and endothelial cell dysfunction. The present study analysed the effects of long-term hyperleptinemia in an in vivo myocardial ischemia-reperfusion model to demonstrate whether the in vivo deleterious effect also affects cardiac structure and function. Main methods Rats were subcutaneously administered leptin for 8 days to estimate the involvement of the JAK/STAT pathway. Data from 58 male Wistar rats were included in the final analysis. Myocardial infarction (MI) was modelled by the 30-minute ligation of the main left coronary artery followed by 120-minute reperfusion. Hemodynamic measurements, electrocardiography monitoring, echocardiography, myocardial infarct size and area at risk, blood biochemical parameters, leptin, IL-6, TNF-alpha, FGF-21, and cardiomyocyte morphology were measured. The expression of JAK2, p-JAK2, STAT3, p-STAT3 was assessed by Western Blot analysis. Statistical analyses were performed using IBM SPSS Statistics v.26. Key findings Eight-day hyperleptinemia in rats leads to an increase in blood pressure and heart rate, myocardial hypertrophy, impaired LV function, the frequency of ischemic arrhythmias, dyslipidemia, systemic inflammation, and the size of induced myocardial infarction. Significance: The blockade of the JAK/STAT signalling pathway effectively reverses the negative effects of leptin, including increased blood pressure and total cholesterol.

The Acute Effects of Leptin on the Contractility of Isolated Rat Atrial and Ventricular Cardiomyocytes

“…It is known that hyperleptinemia in human and animals, including rats, leads to an increase in blood pressure, myocardial hypertrophy, impaired left ventricular function, and arrhythmias [ 12 , 39 , 40 , 41 ]. Previous studies showed that leptin directly depresses ventricular cardiomyocyte contraction through mechanisms related to NO-, JAK-STAT-, and MAPK-signaling pathways [ 13 , 22 , 23 , 42 ].…”

“…Low nanomolar levels of leptin below 10 ng/mL (<1 nM) in rat blood plasma are considered as the physiological range [ 57 ]. Previously, we showed that leptin plasma concentrations in intact male Wistar rats aged 11–12 weeks was 3.0–4.0 ng/mL [ 41 ]. A recent study demonstrated that plasma leptin levels do not reflect cardiac leptin synthesis in the myocardium and may not predict leptin-related cardiovascular morbidity [ 5 ].…”

Leptin and risk factors for atherosclerosis: A review

“…[43] The relationship between leptin and cholesterol was also demonstrated in an animal study where rats had significantly higher total cholesterol levels after being injected subcutaneously with leptin for 8 days. [44] Triglycerides (TG) are another important component of blood lipids, and increased TG levels have been an independent risk factor for AS. [45] Leptin stimulates hepatic secretion of TG via the brain-vagus-hepatic axis.…”

An Overview of Obesity, Cholesterol, and Systemic Inflammation in Preeclampsia

“…Studies in pregnant rodents have elegantly demonstrated the relationship between leptin and other atherogenic factors that are thought to promote inflammation, ischemia, and endothelial dysfunction, all of which are key features of PE [ 34 ]. The subcutaneous administration of leptin to pregnant rats resulted in adverse outcomes such as increased blood pressure, dyslipidemia, endothelial cell dysfunction, and overall increased markers of systemic inflammation [ 34 ].…”