Decreased Expression of Natriuretic Peptides Associated with Lipid Accumulation in Cardiac Ventricle of Obese Mice

Abstract

Plasma B-type natriuretic peptide (BNP) and proBNP are established markers of cardiac dysfunction. Even though obesity increases the risk of cardiovascular disease, obese individuals have reduced plasma concentrations of natriuretic peptides. The underlying mechanism is not established. We used cultured cardiomyocytes and three different mouse models to examine the impact of obesity and cardiac lipid accumulation on cardiac natriuretic peptide expression. The cardiac ventricular expression of atrial natriuretic peptide (ANP) and BNP mRNA and ANP peptide was decreased 36-72% in obese ob/ob, db/db, and fat-fed C57BL/6 mice as compared with their respective controls. The db/db and ob/ob mice displayed impaired cardiac function, whereas the fat-fed mice had almost normal cardiac function. Moreover, the ventricular expression of hypertrophic genes (α- and β-myosin heavy chain and α-actin) and natriuretic peptide receptor genes were not consistently altered by obesity across the three mouse models. In contrast, cardiac ventricular triglycerides were similarly increased by 60-115% in all three obese mouse models and incubation with oleic acid caused triglyceride accumulation and an approximately 35% (P < 0.005) depression of ANP mRNA expression in cultured HL-1 atrial myocytes. The data suggest that obesity and altered cardiac lipid metabolism are associated with reduced production of ANP and BNP in the cardiac ventricles in the setting of normal as well as impaired cardiac function.

A low-carbohydrate high-fat diet decreases lean mass and impairs cardiac function in pair-fed female C57BL/6J mice

“…When carbohydrate intake is reduced, energy must be supplied by other sources, like fatty acid oxidation, that require more oxygen [27, 28]. In our current study, mice fed a LCHF diet showed higher CD36 gene expression as well as higher levels of triglycerides in the myocardium [29, 30]. Similar cardiac alterations have been reported in obese mice fed a long-term high-fat diet [30].…”

“…In the present study the expression of the gene encoding natriuretic protein A (ANP) was significantly lower in the LCHF group. Increased ANP expression is traditionally used as a marker of heart failure [32, 33], but in recent years, decreases in ANP expression concomitantly with increases in the expression of its receptor, NPR-A, have been linked to metabolic dysfunction [29]. Abundant intake of dietary fat decreases ANP expression, and recent findings suggest that disturbances in the endogenous cardiac ANP/NPR-A system might induce cardiomyocyte hypertrophy [29, 32, 33].…”

“…Increased ANP expression is traditionally used as a marker of heart failure [32, 33], but in recent years, decreases in ANP expression concomitantly with increases in the expression of its receptor, NPR-A, have been linked to metabolic dysfunction [29]. Abundant intake of dietary fat decreases ANP expression, and recent findings suggest that disturbances in the endogenous cardiac ANP/NPR-A system might induce cardiomyocyte hypertrophy [29, 32, 33]. The lower expression of ANP and the higher expression of NPR-A relative to control found in the present study might therefore reflect one way for the myocardium to counteract imminent hypertrophy [30], even though echocardiography showed that hypertrophy was not established after 4 weeks on the LCHF diet [34].…”

“…In humans, there are fewer incidents of obesity-related metabolic disorders prior to menopause in women [47]. However, some obesity-related metabolic alterations are independent of sex, such as changes in ANP and NPR-A levels [29]. Thus, future studies are warranted to investigate possible sex-specific effects of a LCHF diet.…”

Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice

“…Several other studies have used cardiac imaging to evaluate cardiac structure and mechanical function in db/db model. It appears that no consensus is established as some reports show cardiac hypertrophy with systolic and diastolic dysfunction [46,47], whereas others reported no change in cardiac function [20]. Discrepancies between some reports may be due to the duration and the type of diabetes, background mouse strain, gender and anesthesia.…”