Carvedilol improves glucose tolerance and insulin sensitivity in treatment of adrenergic overdrive in high fat diet-induced obesity in mice

Autoři: Linh V. Nguyen aff001;  Quang V. Ta aff002;  Thao B. Dang aff001;  Phu H. Nguyen aff003;  Thach Nguyen aff001;  Thi Van Huyen Pham aff001;  Trang HT. Nguyen aff004;  Stephen Baker aff004;  Trung Le Tran aff005;  Dong Joo Yang aff005;  Ki Woo Kim aff005;  Khanh V. Doan aff001
Působiště autorů: School of Medicine, Tan Tao University, Long An, Viet Nam aff001;  School of Biotechnology, Tan Tao University, Long An, Viet Nam aff002;  Binh Dan Hospital, Ho Chi Minh, Viet Nam aff003;  Oxford University Clinical Research Unit in Viet Nam, Ho Chi Minh, Viet Nam aff004;  Division of Physiology, Department of Oral Biology, BK21 PLUS, Yonsei University College of Dentistry, Seoul, South Korea aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224674


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.

Klíčová slova:

Blood plasma – Body weight – Catecholamines – Glucose metabolism – Insulin – leptin – Obesity – Norepinephrine


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