β3‐Adrenergic Activation Improves Maternal and Offspring Perinatal Outcomes in Diet‐Induced Prepregnancy Obesity in Mice

Abstract

Objective Prepregnancy obesity is an epidemic disorder that seriously threatens both maternal and offspring health. This study investigated the effects of β3‐adrenergic receptor (β3‐AR) activation on the perinatal outcomes in a diet‐induced prepregnancy obese (PPO) murine model. Methods Four‐week‐old female C57BL/6 mice were fed high‐fat diet or chow diet for 16 weeks to yield PPO mice and chow‐fed (CF) lean mice, respectively. After successful mating with CF males, the PPO and CF mice were both randomly divided into vehicle control‐ or CL316,243 (a highly selective β3‐AR agonist)‐treated groups. On gestational day 7, subcutaneous infusion of CL316,243 or saline vehicle (1 mg/kg/d) was provided using osmotic pumps. The perinatal outcomes, adipose tissue morphology, and metabolic and inflammatory markers were examined. Results Chronic β3‐AR agonist infusion induced brown adipose tissue activation and white adipose tissue browning and countered obesity‐induced alterations in lipid profiles, insulin resistance, and systemic and local inflammatory states. Moreover, β3‐AR activation was associated with improved placental perfusion and offspring outcomes. Conclusions Our results provide proof‐of‐principle evidence that pharmacological β3‐AR activation may be of therapeutic potential in preventing prepregnancy‐obesity‐associated adverse maternal and offspring perinatal outcomes.

Sesamol promotes browning of white adipocytes to ameliorate obesity by inducing mitochondrial biogenesis and inhibition mitophagy via β3-AR/PKA signaling pathway

“…Therefore, if mitochondrial biogenesis got increased while mitophagy could be inhibited, it would be an ideal strategy for increasing beige adipocyte to promote energy consumption and treat obesity (16)(17)(18). Recent researches have shown that the β3-AR and its downstream PKA could drive the 'browning' effect in WAT, and some studies demonstrated that the activation of PKA would lead to promote mitochondrial biogenesis or inhibit mitophagy (19,20).…”