April 24th, 2013
Adiposity and Natriuretic Peptides: Where Does the Fat Go?
Ian Neeland, MD
In a study recently published online by JACC, investigators assess the association between natriuretic peptide levels and body-fat distribution. Ian Neeland, the lead author of the study, responds to John Ryan’s questions.
THE STUDY
The researchers used data from the Dallas Heart Study to conduct a cross-sectional analysis of BNP and NT-proBNP levels and various measures of body fat and adiposity (e.g., BMI, total body fat, lean mass, lower-body fat, visceral and subcutaneous fat, and liver fat) in 2619 participants without clinical heart failure. Both NT-proBNP and BNP levels were inversely associated with visceral fat and liver fat and positively associated with lower-body fat.
THE AUTHOR RESPONDS
Ryan: Why did you do this study?
Neeland: I’m interested in the relationship between body-fat distribution and cardiovascular health, especially with regard to obesity. Although it is fairly well established now that increased adipose tissue may have adverse cardiac effects, the scientific community is just starting to recognize that this is a bidirectional process — the heart can also exert effects on adipose tissue through secretion of natriuretic peptides. In animals, BNP can stimulate lipolysis, leading to dissolution of fat stores, and can also alter body-fat distribution. Since this work has not yet been translated to humans, we wanted to investigate the relationship between BNP and NT-proBNP levels and fat distribution (assessed by MRI and DEXA imaging) in adults without heart failure. We found that higher natriuretic peptide levels (still within the physiologic range) were associated with less visceral and liver fat (both linked to cardiometabolic disease) and with more lower-body subcutaneous fat, which is a “healthy” fat depot. This suggested to us that natriuretic peptides secreted by the heart may exert beneficial effects on fat metabolism in humans.
Ryan: In your study, a low BNP was associated with increased visceral adiposity. What is the proposed mechanism behind this?
Neeland: Visceral fat is probably much more sensitive than lower-body subcutaneous fat to the lipolytic effects of BNP. When BNP is relatively deficient (such as in obesity), visceral fat may begin to accumulate. This could cause both increased clearance of BNP from the bloodstream and lipotoxicity-induced suppression of BNP synthesis and release from the heart. Chronically low levels of BNP would then result in more visceral fat accumulation, and the cycle could go on and on.
Ryan: You have previously shown that excess adiposity in the lower body is associated with a lower prevalence of metabolic risk factors. Do you think that the interaction of BNP with fat plays a prognostic role in this association?
Neeland: The link between greater amounts of lower-body fat and metabolic health is an exciting area of research right now. It’s long been recognized that women have higher BNP levels than men. Women also have more lower-body fat and less visceral fat than men. It’s plausible that higher natriuretic peptide levels in women could positively influence fat distribution into the lower-body compartment rather than the abdomen, which may explain some of the difference in cardiovascular prognosis between the sexes.
Ryan: If a patient in overt heart failure who is also obese is found to have a low BNP, should we be screening for metabolic syndrome or diabetes?
Neeland: Although it’s certainly intriguing to speculate that low BNP levels in patients with obesity and heart failure reflect underlying metabolic disease, our study does not address the heart-failure population. BNP related to heart failure may be a totally different animal than physiologic BNP. In fact, patients with advanced heart failure with very high BNP levels tend to be lipodystrophic, with abnormal adipose tissue biology resulting in muscle and fat wasting, and don’t demonstrate favorable adiposity profiles at all.
Ryan: What therapeutic potential might energe from this work on BNP and fat distribution?
Neeland: First, if natriuretic peptides truly alter fat distribution in humans, we could potentially treat abdominal obesity by increasing BNP levels. Levels can be increased by administering recombinant BNP, stimulating BNP synthesis, or inhibiting the catabolism and clearance of BNP. This approach has failed to improve heart-failure outcomes in the past (e.g., omapatrilat and nesiritide) but may still hold promise for obesity. Also, our study may partially explain the beneficial effects of physical activity in treating the metabolic syndrome, since exercise both enhances natriuretic peptide release and preferentially reduces visceral fat mass.
2 Responses to “Adiposity and Natriuretic Peptides: Where Does the Fat Go?”
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BNP levels were previously known to be lower for a given LVEDP in obese patients. The intriguing new information suggests that it is visceral fat that is associated with this phenomenon rather than SC fat. Is there evidence that visceral fat clears BNP more than SC fat? Why should we infer that BNP has any causal role in fat distribution?
Great questions! To answer your first question: Yes, there is evidence of this – experimental models show that visceral fat expresses more NPR-C (clearance) receptors than SC fat so clearance of BNP is upregulated in visceral fat depots. To answer your second question, although not definitively shown to have a causal role in humans, animal models have consistently demonstrated that infusions of BNP or upregulation of BNP through genetic modification in rodents causes beneficial changes in fat metabolism and distribution. These interesting findings led us to perform this study, which he hope can generate some additional hypotheses going forward.