Natriuretic peptide control of energy balance and glucose homeostasis

• Natriuretic peptide plasma levels predict the risk of new onset type 2 diabetes.
• Natriuretic peptides enhance fat balance and energy expenditure.
• Natriuretic peptides improve blood glucose control in mouse models of obesity and type 2 diabetes.
• Targeting the natriuretic peptide system may have a therapeutic potential in obesity.

Cardiac natriuretic peptides (NP) have recently emerged as metabolic hormones. Physiological stimulation of cardiac NP release as during exercise may contribute to increase fatty acid mobilization from adipose tissue and their oxidation by skeletal muscles. Clinical studies have shown that although very high plasma NP level characterizes cardiac dysfunction and heart failure, a consistently reduced plasma NP level is observed in metabolic diseases such as obesity and type 2 diabetes. A low circulating NP level also predicts the risk of new onset type 2 diabetes. It is unclear at this stage if the “natriuretic handicap” observed in obesity is causally associated with the incidence of type 2 diabetes. Recent work indicates that NP can activate a thermogenic program in brown and white fat, increase energy expenditure and inhibit food intake. Mouse studies also argue for a key role of NP in the regulation of energy balance and glucose homeostasis. This review will focus on recent human and mouse studies to highlight the metabolic roles of NP and their potential relevance in the context of obesity and type 2 diabetes.