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Natriuretic peptides/cGMP/cGMP-dependent protein kinase cascades promote muscle mitochondrial biogenesis and prevent obesity.
- Source :
-
Diabetes [Diabetes] 2009 Dec; Vol. 58 (12), pp. 2880-92. Date of Electronic Publication: 2009 Aug 18. - Publication Year :
- 2009
-
Abstract
- Objective: Natriuretic peptides (NPs) have been characterized as vascular hormones that regulate vascular tone via guanylyl cyclase (GC), cyclic GMP (cGMP), and cGMP-dependent protein kinase (cGK). Recent clinical studies have shown that plasma NP levels were lower in subjects with the metabolic syndrome. The present study was conducted to elucidate the roles for NP/cGK cascades in energy metabolism.<br />Research Design and Methods: We used three types of genetically engineered mice: brain NP (BNP) transgenic (BNP-Tg), cGK-Tg, and guanylyl cyclase-A (GCA) heterozygous knockout (GCA(+/-)) mice and analyzed the metabolic consequences of chronic activation of NP/cGK cascades in vivo. We also examined the effect of NPs in cultured myocytes.<br />Results: BNP-Tg mice fed on high-fat diet were protected against diet-induced obesity and insulin resistance, and cGK-Tg mice had reduced body weight even on standard diet; surprisingly, giant mitochondria were densely packed in the skeletal muscle. Both mice showed an increase in muscle mitochondrial content and fat oxidation through upregulation of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1alpha and PPARdelta. The functional NP receptors, GCA and guanylyl cyclase-B, were downregulated by feeding a high-fat diet, while GCA(+/-) mice showed increases in body weight and glucose intolerance when fed a high-fat diet. NPs directly increased the expression of PGC-1alpha and PPARdelta and mitochondrial content in cultured myocytes.<br />Conclusions: The findings together suggest that NP/cGK cascades can promote muscle mitochondrial biogenesis and fat oxidation, as to prevent obesity and glucose intolerance. The vascular hormone, NP, would contribute to coordinated regulation of oxygen supply and consumption.
- Subjects :
- Animals
Blood Glucose metabolism
Cells, Cultured
Dietary Fats administration & dosage
Dietary Fats adverse effects
Down-Regulation
Genetic Engineering
Glucose Intolerance etiology
Lipid Peroxidation
Mice
Mice, Knockout
Molecular Sequence Data
Muscle Cells metabolism
Natriuretic Peptide, Brain metabolism
Obesity etiology
Obesity metabolism
Oxygen Consumption
PPAR delta metabolism
PPAR gamma metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Receptors, Atrial Natriuretic Factor metabolism
Trans-Activators metabolism
Transcription Factors
Up-Regulation
Cyclic GMP metabolism
Dietary Fats metabolism
Glucose Intolerance metabolism
Insulin Resistance
Mitochondria metabolism
Muscle, Skeletal metabolism
Natriuretic Peptides metabolism
Obesity prevention & control
Protein Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 58
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 19690065
- Full Text :
- https://doi.org/10.2337/db09-0393