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Activation of NPRs and UCP1-independent pathway following CB1R antagonist treatment is associated with adipose tissue beiging in fat-fed male dogs.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2019 Sep 01; Vol. 317 (3), pp. E535-E547. Date of Electronic Publication: 2019 Jun 25. - Publication Year :
- 2019
-
Abstract
- CB1 receptor (CB1R) antagonism improves the deleterious effects of a high-fat diet (HFD) by reducing body fat mass and adipocyte cell size. Previous studies demonstrated that the beneficial effects of the CB1R antagonist rimonabant (RIM) in white adipose tissue (WAT) are partially due to an increase of mitochondria numbers and upregulation thermogenesis markers, suggesting an induction of WAT beiging. However, the molecular mechanism by which CB1R antagonism induces weight loss and WAT beiging is unclear. In this study, we probed for genes associated with beiging and explored longitudinal molecular mechanisms by which the beiging process occurs. HFD dogs received either RIM (HFD+RIM) or placebo (PL) (HFD+PL) for 16 wk. Several genes involved in beiging were increased in HFD+RIM compared with pre-fat, HFD, and HFD+PL. We evaluated lipolysis and its regulators including natriuretic peptide (NP) and its receptors ( NPRs ), β-1 and β-3 adrenergic receptor ( β1R , β3R ) genes. These genes were increased in WAT depots, accompanied by an increase in lipolysis in HFD+RIM. In addition, RIM decreased markers of inflammation and increased adiponectin receptors in WAT. We observed a small but significant increase in UCP1 ; therefore, we evaluated the newly discovered UCP1-independent thermogenesis pathway. We confirmed that SERCA2b and RYR2 , the two key genes involved in this pathway, were upregulated in the WAT. Our data suggest that the upregulation of NPRs , β-1R and β-3R , lipolysis, and SERCA2b and RYR2 may be one of the mechanisms by which RIM promotes beiging and overall the improvement of metabolic homeostasis induced by RIM.
- Subjects :
- Animals
Dogs
Gene Expression drug effects
Inflammation pathology
Inflammation prevention & control
Insulin Resistance
Male
Organelle Biogenesis
Receptors, Adrenergic, beta drug effects
Receptors, Adrenergic, beta metabolism
Rimonabant pharmacology
Thermogenesis drug effects
Thermogenesis genetics
Weight Loss drug effects
Adipose Tissue drug effects
Adipose Tissue, Brown drug effects
Adipose Tissue, White drug effects
Diet, High-Fat adverse effects
Receptor, Cannabinoid, CB1 antagonists & inhibitors
Receptors, Atrial Natriuretic Factor drug effects
Uncoupling Protein 1 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 317
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 31237449
- Full Text :
- https://doi.org/10.1152/ajpendo.00539.2018