An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Abstract

Abstract-In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. (ATP III). The NCEP definition of the metabolic syndrome includes 3 or more of the following: abdominal obesity, defined as waist circumference Ն102 cm in men and Ͼ88 cm in women; elevated triglyceride concentration Ն150 mg/dL, low HDL cholesterol (Ͻ40 mg/dL in men and Ͻ50 mg/dL in women); elevated fasting plasma glucose level (Ն110 mg/dL); and elevated blood pressure (Ն130/85 mm Hg). 1 The presence of abdominal obesity is more closely associated with the metabolic risk factors than body mass index. The prevalence of the metabolic syndrome increases with age. Obesity interferes with many metabolic pathways which underlie numerous potential risk factors. It is very difficult to differentiate between the major and minor factors, and some remain to be discovered. 2 This complexity leaves the area open and challenges basic and clinical researchers to uncover novel metabolic pathways. The discovery that cardiac natriuretic peptides (NPs) control human fat cell function is a provocative observation which reveals an unsuspected link between heart and adipose tissue. NPs exert potent lipolytic effects (eg, stimulation of hydrolysis of triacylglycerols stored in adipocytes) in isolated human fat cells. 3 When administered intravenously, they potently increase plasma glycerol and nonesterified fatty acid (NEFA) levels; in other words they stimulate lipid mobilization. 4 Before the discovery of the NP pathway, catecholamines and insulin were considered to be the major acute regulators of lipid mobilization in humans: they both act through a cAMP-dependent regulation of lipolysis. In contrast, NPs activate a 3Ј, 5Ј-cyclic guanosine monophosphate (cGMP)-dependent pathway that is completely independent from the cAMP-dependent pathway. 5 The NPs may represent a promising new pathway contributing to the control of lipid mobilization in humans in physiological and pathological conditions. The introductory section

Relationship between N-terminal pro-B-type natriuretic peptide levels and metabolic syndrome

“…Consistent with prior experimental observations [12], we found that there is a strong relationship between serum NT-proBNP and plasma triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol levels, suggesting a strong relationship between NT-proBNP and lipid metabolism. An inverse relationship between serum NT-proBNP and cholesterol has been described previously and has been hypothesized to be a potential link impairing the natural blood pressure regulation [6].…”

Development and Validation of Risk Prediction Models for Cardiovascular Events in Black Adults

“…37 The natriuretic peptide system also influences lipid and glucose metabolism and homeostasis, further potentially contributing to the prognostic value of BNP. 38–41 …”

Obesity and natriuretic peptides, BNP and NT-proBNP: Mechanisms and diagnostic implications for heart failure

“…In this context, it is of interest to note that calorie restriction promotes muscle mitochondrial biogenesis in rodents [106] as well as humans [107] by increasing the levels of nitric oxide, the upstream activator of cGMP/cGK1 pathway. Emerging evidence suggests that natriuretic peptides control lipolysis and lipid mobilization in physiological and pathological conditions [108]. Further supporting the protective effect of natriuretic peptides against obesity, Sengenés et al [92] reported that cardiac natriuretic peptides induce strong lipolysis in isolated human fat cells by producing cGMP via the NPR-A receptor.…”