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Sci Signal. 2017 Jul 25;10(489). pii: eaam6870. doi: 10.1126/scisignal.aam6870.

Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle, protects against diet-induced obesity and insulin resistance.

Author information

1
Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, FL 32827, USA.
2
Division of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai 200040, China.
3
Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, FL 32827, USA.
4
Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, FL 32827, USA. scollins@sbpdiscovery.org.

Abstract

In addition to controlling blood pressure, cardiac natriuretic peptides (NPs) can stimulate lipolysis in adipocytes and promote the "browning" of white adipose tissue. NPs may also increase the oxidative capacity of skeletal muscle. To unravel the contribution of NP-stimulated metabolism in adipose tissue compared to that in muscle in vivo, we generated mice with tissue-specific deletion of the NP clearance receptor, NPRC, in adipose tissue (NprcAKO ) or in skeletal muscle (NprcMKO ). We showed that, similar to Nprc null mice, NprcAKO mice, but not NprcMKO mice, were resistant to obesity induced by a high-fat diet. NprcAKO mice exhibited increased energy expenditure, improved insulin sensitivity, and increased glucose uptake into brown fat. These mice were also protected from diet-induced hepatic steatosis and visceral fat inflammation. These findings support the conclusion that NPRC in adipose tissue is a critical regulator of energy metabolism and suggest that inhibiting this receptor may be an important avenue to explore for combating metabolic disease.

PMID:
28743802
DOI:
10.1126/scisignal.aam6870
[Indexed for MEDLINE]

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