Direct actions of Brain Natriuretic Peptide (BNP) on brown adipose tissue include stimulation of Monocyte Chemoattractant Protein-1 (MCP-1), angiotensin II, and leptin

Brain natriuretic peptide (BNP) regulates salt/water balance and vascular tone. Blood levels of this hormone are clinically used as a sensitive marker for cardiac failure, a major complication of the metabolic syndrome. Adipose tissue plays a key role in the pathogenesis of the metabolic syndrome. Brown adipose tissue has been implicated in the development of insulin resistance and obesity in humans and represents a potential therapeutic target tissue. We investigated direct effects of BNP on thermogenesis, differentiation, insulin sensitivity, and endocrine activity in SV40T-immortalized brown adipocytes. Thermogenic function and adipocyte differentiation were unchanged by BNP treatment as measured by UCP-1 mRNA as well as protein expression and Oil Red O staining, respectively. Furthermore, treatment of differentiated cells with BNP (1µM) from 1 to 24h did not change the insulin-induced glucose-uptake. Consistent with these findings, phosphorylation of signaling molecules mediating insulin's metabolic effects such as Akt, p70S6 or pGSK3 was not significantly altered by acute BNP treatment. However, BNP treatment from 1 to 40 minutes time- and dose-dependently resulted in activation of MAP kinase by maximally 400% after 5 minutes (p<0.01). Furthermore, expression of inflammatory and vasoregulatory adipokines was altered. Thus, monocyte chemoattractant protein-1 (MCP-1) was increased by 60% after 2h of BNP treatment (100 nM, p<0.05). BNP also increased mRNA expression of angiotensin II by 80% and leptin by 40% (p<0.05 and <0.01, respectively). In contrast, adiponectin mRNA levels remained unchanged. Taken together, our data suggest selective direct effects of BNP on the endocrine activity of adipose tissue. These direct actions include the stimulation of inflammatory adipokines such as MCP-1 which is involved in the development of insulin resistance. Thus, this may have implications for the pathogenesis of the metabolic syndrome and its associated cardiovascular complications.