Tschimganidine reduces lipid accumulation through AMPK activation and alleviates high-fat diet-induced metabolic diseases
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Obesity increases the risk of mortality and morbidity becauseit results in hypertension, heart disease, and type 2 diabetes. Therefore, there is an urgent need for pharmacotherapeutic drugsto treat obesity. We performed a screening assay using naturalproducts with anti-adipogenic properties in 3T3-L1 cells anddetermined that tschimganidine, a terpenoid from the Umbelliferaefamily, inhibited adipogenesis. To evaluate the anti-obesityeffects of tschimganidine in vivo. Mice were fed either anormal chow diet (NFD) or a high-fat chow diet (HFD) with orwithout tschimganidine for 12 weeks. Treatment with tschimganidinedecreased lipid accumulation and adipogenesis, accompaniedby reduced expression of adipogenesis and lipid accumulation-related factors. Tschimganidine significantly increasedthe phosphorylation of AMP-activated protein kinase (AMPK)and decreased that of AKT. Depletion of AMPK relieved thereduction in lipid accumulation resulting from tschimganidinetreatment. Moreover, tschimganidine administration drasticallyreduced the weight and size of both gonadal white adiposetissue (WAT) and blood glucose levels in high-fat diet-inducedobese mice. We suggest that tschimganidine is a potent antiobesityagent, which impedes adipogenesis and improves glucosehomeostasis. Tschimganidine can then be evaluated forclinical application as a therapeutic agent.
Abstract
Obesity increases the risk of mortality and morbidity becauseit results in hypertension, heart disease, and type 2 diabetes. Therefore, there is an urgent need for pharmacotherapeutic drugsto treat obesity. We performed a screening assay using naturalproducts with anti-adipogenic properties in 3T3-L1 cells anddetermined that tschimganidine, a terpenoid from the Umbelliferaefamily, inhibited adipogenesis. To evaluate the anti-obesityeffects of tschimganidine in vivo. Mice were fed either anormal chow diet (NFD) or a high-fat chow diet (HFD) with orwithout tschimganidine for 12 weeks. Treatment with tschimganidinedecreased lipid accumulation and adipogenesis, accompaniedby reduced expression of adipogenesis and lipid accumulation-related factors. Tschimganidine significantly increasedthe phosphorylation of AMP-activated protein kinase (AMPK)and decreased that of AKT. Depletion of AMPK relieved thereduction in lipid accumulation resulting from tschimganidinetreatment. Moreover, tschimganidine administration drasticallyreduced the weight and size of both gonadal white adiposetissue (WAT) and blood glucose levels in high-fat diet-inducedobese mice. We suggest that tschimganidine is a potent antiobesityagent, which impedes adipogenesis and improves glucosehomeostasis. Tschimganidine can then be evaluated forclinical application as a therapeutic agent.
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