Combining a β3 adrenergic receptor agonist with alpha‐lipoic acid reduces inflammation in male mice with diet‐induced obesity

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.

Identification of cuproptosis-related subtypes, characterization of immune microenvironment infiltration, and development of a prognosis model for osteoarthritis

“…LIPT1 is a vital gene encoding the mitochondrial lipoic acid pathway (9). Abdul et al (18) reported that lipoic acid reduces obesity-induced inflammation in the body by modulating the immune system when chronic treatment with lipoic acid agonists is administered. In addition, the synthesis of mitochondrial fatty is inextricably linked to LIPT1 expression (19).…”

Rearing conditions impacted efficacy of α-lipoic acid to influence longevity in Drosophila melanogaster fed with a high fat diet

“…Discontinuous treatment of Sprague-Dawley rats with α-lipoic acid at 50 mg/kg body weight prevented gain in body weight and had a protective e cacy on the cardiovascular system by decreasing metabolic and cardiac perturbations (Pop et al, 2020). In another study, chronic treatment of diet induced obese mice with 250 mg/kg of α-lipoic acid in combination with β3-AR agonist CL 316,243 improved body mass composition, reduced body fat percentage by 9% and improved systemic and epididymal white adipose tissue in ammation (Abdul Sater et al, 2022). C57Bl/6J mice fed with a high fat diet and administered with α-lipoic acid at 2.5g/kg of food in conjunction with exercise on treadmill showed improved fatty acid oxidation and reduced visceral adipose tissue (Le Garf et al, 2021).…”