Editors' ChoiceMetabolism

The Promise of C-Type Natriuretic Peptide for Weight Loss

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Science Translational Medicine  04 Aug 2010:
Vol. 2, Issue 43, pp. 43ec122
DOI: 10.1126/scitranslmed.3001524

What is the secret to slimming? The latest candidate is C-type natriuretic peptide (CNP), a brain hormone active in the nervous system of animals that also regulates the vascular and skeletal systems. The exact function of CNP is unclear, but it’s found in the hypothalamus, a brain center known to control food and energy intake. Inuzuka et al. investigated whether CNP regulates body weight and metabolism; however, they had to be creative in their approach.

These investigators have shown that mice that lack the gene for either CNP or its receptor exhibit skeletal deformities as well as low body weight and premature death. Rather than assuming that the low body weight was simply secondary to eating problems caused by poor tooth and jaw development, Inuzuka et al. engineered mice that expressed CNP only in the cells responsible for bone formation in order to examine the hormone’s effect on body weight and metabolism in isolation. When the mice were 20 weeks old, the author measured metabolic parameters: body fat; concentrations of blood glucose, insulin, and ghrelin; urinary noradrenalin; food intake; oxygen consumption and locomotor activity. Mice without CNP were 24% smaller and had 50% less body fat than their CNP-replete brethren. CNP-deficient mice were also more insulin sensitive, had lower blood leptin and higher blood ghrelin, and ate 21% less food than control mice. Without being more active, they also consumed more oxygen and excreted more urinary noradrenalin.

The striking metabolic effects of this hormone illustrate how the use of genetic engineering can lend insight into physiological processes otherwise not able to be examined due to the natural biological course of disease. These results now set the stage for examining CNP and its effects in humans.

M. Inuzuka et al., C-type natriuretic peptide as a new regulator of food intake and energy expenditure. Endocrinology 151, 3633–3642 (2010). [Abstract]

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