Zahraa Abdul Sater1, Cheryl Cero1, Anne E Pierce1, Hannah J Lea1, Houssein Abdul Sater2, Kenneth Y Zhu1, Naili Liu3, Yinyan Ma3, Oksana Gavrilova3, Aaron M Cypess1. 1. Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. 2. Medical Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. 3. Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Abstract
OBJECTIVES: Beta-3 adrenergic receptors (β3-AR) stimulate lipolysis and thermogenesis in white and brown adipose tissue (WAT and BAT). Obesity increases oxidative stress and inflammation that attenuate AT β3-AR signaling. The objective of this study was to test the hypothesis that the combination of the β3-AR agonist CL-316,243 (CL) and the antioxidant alpha-lipoic acid (ALA) would lower inflammation in diet-induced obesity (DIO) and improve β3-AR function. METHODS: A total of 40 DIO mice were separated into four groups: Control (per os and intraperitoneal [IP] vehicle); CL alone (0.01 mg/kg IP daily); ALA alone (250 mg/kg in drinking water); or ALA+CL combination, all for 5 weeks. RESULTS: Food intake was similar in all groups; however, mice receiving ALA+CL showed improved body composition and inflammation as well as lower body weight (+1.7 g Control vs. -2.5 g ALA+CL [-7%]; p < 0.01) and percentage of body fat (-9%, p < 0.001). Systemic and epididymal WAT inflammation was lower with ALA+CL than all other groups, with enhanced recruitment of epididymal WAT anti-inflammatory CD206+ M2 macrophages. β3-AR signaling in WAT was enhanced in the combination-treatment group, with higher mRNA and protein levels of thermogenic uncoupling protein 1 and AT lipases. CONCLUSIONS: Chronic treatment with ALA and a β3-AR agonist reduces DIO-induced inflammation. AT immune modulation could be a therapeutic target in patients with obesity. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.
OBJECTIVES: Beta-3 adrenergic receptors (β3-AR) stimulate lipolysis and thermogenesis in white and brown adipose tissue (WAT and BAT). Obesity increases oxidative stress and inflammation that attenuate AT β3-AR signaling. The objective of this study was to test the hypothesis that the combination of the β3-AR agonist CL-316,243 (CL) and the antioxidant alpha-lipoic acid (ALA) would lower inflammation in diet-induced obesity (DIO) and improve β3-AR function. METHODS: A total of 40 DIO mice were separated into four groups: Control (per os and intraperitoneal [IP] vehicle); CL alone (0.01 mg/kg IP daily); ALA alone (250 mg/kg in drinking water); or ALA+CL combination, all for 5 weeks. RESULTS: Food intake was similar in all groups; however, mice receiving ALA+CL showed improved body composition and inflammation as well as lower body weight (+1.7 g Control vs. -2.5 g ALA+CL [-7%]; p < 0.01) and percentage of body fat (-9%, p < 0.001). Systemic and epididymal WAT inflammation was lower with ALA+CL than all other groups, with enhanced recruitment of epididymal WAT anti-inflammatory CD206+ M2 macrophages. β3-AR signaling in WAT was enhanced in the combination-treatment group, with higher mRNA and protein levels of thermogenic uncoupling protein 1 and AT lipases. CONCLUSIONS: Chronic treatment with ALA and a β3-AR agonist reduces DIO-induced inflammation. AT immune modulation could be a therapeutic target in patients with obesity. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.
Authors: Gerd Bobe; Alexander J Michels; Wei-Jian Zhang; Jonathan Q Purnell; Clive Woffendin; Cliff Pereira; Joseph A Vita; Nicholas O Thomas; Maret G Traber; Balz Frei; Tory M Hagen Journal: J Nutr Date: 2020-09-01 Impact factor: 4.798