Multifaceted effects of guggulsterone as an anti-obesity agent.
Start Date
10-5-2016 1:00 PM
Description
Obesity is associated with pathological expansion of white adipose tissue (WAT) and is the leading cause of morbidity and mortality worldwide. In this study, we explored the multifaceted effects of guggulsterone (GS), a well-studied phytosterol for its cholesterol lowering effects, as an anti-obesity agent. We investigated the effects of GS on adipogenesis, lipolysis and beiging using 3T3-L1 murine adipocyte cell line. Identification of clusters of brown adipocyte-like cells in white adipose tissue depots indicate a mechanism by which WAT acquires brown adipose tissue (BAT)-like properties, generally referred to as 'beiging'. Beiging of WAT increases energy expenditure and is gaining attention as a novel therapeutic approach for obesity. We demonstrate the three-way anti-obesity effects of GS in our in vitro cell culture model. Firstly, GS inhibited the differentiation of preadipocytes to mature adipocytes contributing to the overall decrease in adipogenesis. Secondly, GS promoted lipolysis in mature adipocytes as evidenced by the increase in free glycerol release with GS treatment. Finally, we have demonstrated the effects of GS on upregulating beige specific markers in mature adipocytes like uncoupling protein 1 (UCP1) and T-box transcription factor 1 (Tbx1) and thermogenic markers like peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), peroxisome proliferator-activated receptor gamma (PPARγ), ZIC1 and SIRT1. GS is structurally similar to bile acids and we hypothesize that GS-induced effects on adipocytes are mediated through, TGR5, a bile acid receptor. Our preliminary results indicate that GS increases TGR5 and type 2 deiodinase (DIO2), a downstream marker of TGR5 activation, expression in mature adipocytes. Together, these data suggest that guggulsterone may exert anti-obesity effects not only by decreasing adipogenesis and promoting lipolysis in WAT, but also by inducing white to beige transdifferentiation thereby increasing thermogenesis and promoting weight loss.
Multifaceted effects of guggulsterone as an anti-obesity agent.
Obesity is associated with pathological expansion of white adipose tissue (WAT) and is the leading cause of morbidity and mortality worldwide. In this study, we explored the multifaceted effects of guggulsterone (GS), a well-studied phytosterol for its cholesterol lowering effects, as an anti-obesity agent. We investigated the effects of GS on adipogenesis, lipolysis and beiging using 3T3-L1 murine adipocyte cell line. Identification of clusters of brown adipocyte-like cells in white adipose tissue depots indicate a mechanism by which WAT acquires brown adipose tissue (BAT)-like properties, generally referred to as 'beiging'. Beiging of WAT increases energy expenditure and is gaining attention as a novel therapeutic approach for obesity. We demonstrate the three-way anti-obesity effects of GS in our in vitro cell culture model. Firstly, GS inhibited the differentiation of preadipocytes to mature adipocytes contributing to the overall decrease in adipogenesis. Secondly, GS promoted lipolysis in mature adipocytes as evidenced by the increase in free glycerol release with GS treatment. Finally, we have demonstrated the effects of GS on upregulating beige specific markers in mature adipocytes like uncoupling protein 1 (UCP1) and T-box transcription factor 1 (Tbx1) and thermogenic markers like peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), peroxisome proliferator-activated receptor gamma (PPARγ), ZIC1 and SIRT1. GS is structurally similar to bile acids and we hypothesize that GS-induced effects on adipocytes are mediated through, TGR5, a bile acid receptor. Our preliminary results indicate that GS increases TGR5 and type 2 deiodinase (DIO2), a downstream marker of TGR5 activation, expression in mature adipocytes. Together, these data suggest that guggulsterone may exert anti-obesity effects not only by decreasing adipogenesis and promoting lipolysis in WAT, but also by inducing white to beige transdifferentiation thereby increasing thermogenesis and promoting weight loss.