Catecholamine excess reflecting an adrenergic overdrive of the sympathetic nervous system (SNS) has been proposed to link to hyperleptinemia in obesity and may contribute to the development of metabolic disorders. However, relationship between the catecholamine level and plasma leptin in obesity has not yet been investigated. Moreover, whether pharmacological blockade of the adrenergic overdrive in obesity by the third-generation beta-blocker agents such as carvedilol could help to prevent metabolic disorders is controversial and remains to be determined. Using the high fat diet (HFD)-induced obese mouse model, we found that basal plasma norepinephrine, the principal catecholamine as an index of SNS activity, was persistently elevated and highly correlated with plasma leptin concentration during obesity development. Targeting the adrenergic overdrive from this chronic norepinephrine excess in HFD-induced obesity with carvedilol, a third-generation beta-blocker with vasodilating action, blunted the HFD-induced hepatic glucose over-production by suppressing the induction of gluconeogenic enzymes, and enhanced the muscular insulin signaling pathway. Furthermore, carvedilol treatment in HFD-induced obese mice decreased the enlargement of white adipose tissue and improved the glucose tolerance and insulin sensitivity without affecting body weight and blood glucose levels. Our results suggested that catecholamine excess in obesity might directly link to the hyperleptinemic condition and the therapeutic targeting of chronic adrenergic overdrive in obesity with carvedilol might be helpful to attenuate obesity-related metabolic disorders.
Bibliographical noteFunding Information:
This research was funded by the Viet Nam National Foundation for Science and Technology (NAFOSTED 108.05-2017.01 to KVD), URL: https://nafosted.gov.vn/en/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Mr. Nguyen Huu Dung (Pharmacist, R&D Boston Pharmaceutical Co., Viet Nam) for his generous providing of carvedilol active pharmaceutical ingredient. We are grateful to Mr. Isaac Smith (M.A, School of Humanities and Languages, Tan Tao University, Viet Nam) for his language editing of the manuscript.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)