Vila et al. (1) reported that brain natriuretic peptide (BNP) infusions reduce total and acylated-ghrelin levels while increasing satiety. Since ghrelin acts orexigenic, the authors conclude that BNP might indirectly regulate food intake in conditions associated with excessive BNP levels, such as in heart failure. The hypothesis is provocative but ignores the complex metabolic actions of natriuretic peptides.

Because ghrelin stimulates hypothalamic AMP-activated protein kinase (AMPK) activity, reduced ghrelin promotes satiety, attenuating food intake. However, other factors could be involved as well. Insulin, glucose, and specific fatty acids inhibit central AMPK activity, also promoting satiety. Atrial natriuretic peptide and BNP potently stimulate human adipose tissue lipolysis (24). Resulting fatty acid release is associated with increased circulating insulin concentrations (57). Furthermore, natriuretic peptides induce lipid oxidation and energy expenditure in mice (8,9) and men (5). Increased hepatic lipid oxidation generates β-hydroxybutyrate (5), which also affects food intake. Thus, natriuretic peptides affect several important mechanisms involved in the regulation of food intake independently of ghrelin. Moreover, natriuretic peptide–induced changes in insulin could indirectly regulate ghrelin (10).

Besides, the hypothesis that BNP has a crucial role in the regulation of food intake is challenged by observations in mice transgenically overexpressing BNP. These animals show chronically elevated BNP plasma concentrations comparable to levels attained with BNP infusions in clinical studies. Yet, feeding behavior and food intake are completely normal (8). Therefore, it is premature to conclude that natriuretic peptides regulate satiety and food intake through ghrelin. Integrative human studies are required that take into account the wide spectrum of metabolic actions elicited by natriuretic peptides.

A.L.B. is supported by a grant from the German Research Foundation (BI1292/4-1).

No potential conflicts of interest relevant to this article were reported.

1.
Vila
G
,
Grimm
G
,
Resl
M
, et al
.
B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men
.
Diabetes
2012
;
61
:
2592
2596
2.
Lafontan
M
,
Moro
C
,
Berlan
M
,
Crampes
F
,
Sengenes
C
,
Galitzky
J
.
Control of lipolysis by natriuretic peptides and cyclic GMP
.
Trends Endocrinol Metab
2008
;
19
:
130
137
3.
Polak
J
,
Kotrc
M
,
Wedellova
Z
, et al
.
Lipolytic effects of B-type natriuretic peptide 1-32 in adipose tissue of heart failure patients compared with healthy controls
.
J Am Coll Cardiol
2011
;
58
:
1119
1125
4.
Birkenfeld
AL
,
Boschmann
M
,
Moro
C
, et al
.
Lipid mobilization with physiological atrial natriuretic peptide concentrations in humans
.
J Clin Endocrinol Metab
2005
;
90
:
3622
3628
5.
Birkenfeld
AL
,
Budziarek
P
,
Boschmann
M
, et al
.
Atrial natriuretic peptide induces postprandial lipid oxidation in humans
.
Diabetes
2008
;
57
:
3199
3204
6.
Birkenfeld
AL
,
Boschmann
M
,
Moro
C
, et al
.
Beta-adrenergic and atrial natriuretic peptide interactions on human cardiovascular and metabolic regulation
.
J Clin Endocrinol Metab
2006
;
91
:
5069
5075
7.
Uehlinger
DE
,
Weidmann
P
,
Gnädinger
MP
, et al
.
Increase in circulating insulin induced by atrial natriuretic peptide in normal humans
.
J Cardiovasc Pharmacol
1986
;
8
:
1122
1129
8.
Miyashita
K
,
Itoh
H
,
Tsujimoto
H
, et al
.
Natriuretic peptides/cGMP/cGMP-dependent protein kinase cascades promote muscle mitochondrial biogenesis and prevent obesity
.
Diabetes
2009
;
58
:
2880
2892
9.
Bordicchia
M
,
Liu
D
,
Amri
EZ
, et al
.
Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes
.
J Clin Invest
2012
;
122
:
1022
1036
10.
Möhlig
M
,
Spranger
J
,
Otto
B
,
Ristow
M
,
Tschöp
M
,
Pfeiffer
AF
.
Euglycemic hyperinsulinemia, but not lipid infusion, decreases circulating ghrelin levels in humans
.
J Endocrinol Invest
2002
;
25
:
RC36
RC38
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