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

Linh V. Nguyen, Quang V. Ta, Thao B. Dang, Phu H. Nguyen, Thach Nguyen, Thi Van Huyen Pham, Trang H.T. Nguyen, Stephen Baker, Trung Le Tran, Dong Joo Yang, Ki Woo Kim, Khanh V. Doan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere0224674
JournalPloS one
Volume14
Issue number11
DOIs
Publication statusPublished - 2019 Jan 1

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High Fat Diet
glucose tolerance
high fat diet
Nutrition
insulin resistance
Adrenergic Agents
Catecholamines
Insulin Resistance
obesity
Obesity
Fats
Insulin
Glucose
mice
Neurology
catecholamines
Leptin
Plasmas
Norepinephrine
metabolic diseases

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Nguyen, L. V., Ta, Q. V., Dang, T. B., Nguyen, P. H., Nguyen, T., Pham, T. V. H., ... Doan, K. V. (2019). Carvedilol improves glucose tolerance and insulin sensitivity in treatment of adrenergic overdrive in high fat diet-induced obesity in mice. PloS one, 14(11), [e0224674]. https://doi.org/10.1371/journal.pone.0224674
Nguyen, Linh V. ; Ta, Quang V. ; Dang, Thao B. ; Nguyen, Phu H. ; Nguyen, Thach ; Pham, Thi Van Huyen ; Nguyen, Trang H.T. ; Baker, Stephen ; Le Tran, Trung ; Yang, Dong Joo ; Kim, Ki Woo ; Doan, Khanh V. / Carvedilol improves glucose tolerance and insulin sensitivity in treatment of adrenergic overdrive in high fat diet-induced obesity in mice. In: PloS one. 2019 ; Vol. 14, No. 11.
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Nguyen, LV, Ta, QV, Dang, TB, Nguyen, PH, Nguyen, T, Pham, TVH, Nguyen, THT, Baker, S, Le Tran, T, Yang, DJ, Kim, KW & Doan, KV 2019, 'Carvedilol improves glucose tolerance and insulin sensitivity in treatment of adrenergic overdrive in high fat diet-induced obesity in mice', PloS one, vol. 14, no. 11, e0224674. https://doi.org/10.1371/journal.pone.0224674

Carvedilol improves glucose tolerance and insulin sensitivity in treatment of adrenergic overdrive in high fat diet-induced obesity in mice. / Nguyen, Linh V.; Ta, Quang V.; Dang, Thao B.; Nguyen, Phu H.; Nguyen, Thach; Pham, Thi Van Huyen; Nguyen, Trang H.T.; Baker, Stephen; Le Tran, Trung; Yang, Dong Joo; Kim, Ki Woo; Doan, Khanh V.

In: PloS one, Vol. 14, No. 11, e0224674, 01.01.2019.

Research output: Contribution to journalArticle

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T1 - Carvedilol improves glucose tolerance and insulin sensitivity in treatment of adrenergic overdrive in high fat diet-induced obesity in mice

AU - Nguyen, Linh V.

AU - Ta, Quang V.

AU - Dang, Thao B.

AU - Nguyen, Phu H.

AU - Nguyen, Thach

AU - Pham, Thi Van Huyen

AU - Nguyen, Trang H.T.

AU - Baker, Stephen

AU - Le Tran, Trung

AU - Yang, Dong Joo

AU - Kim, Ki Woo

AU - Doan, Khanh V.

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N2 - 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.

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