Alisol A 24-acetate stimulates lipolysis in 3 T3-L1 adipocytes

Abstract

Background Alisol A 24-acetate (AA-24-a), one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., exhibits multiple biological activities including hypolipidemic activity. However, its effect on lipid metabolism in adipocytes remains unclear. The present study aimed to clarify the effect of AA-24-a on adipocyte lipolysis and to determine its potential mechanism of action using 3 T3-L1 cells. Methods We assayed the release of glycerol into culture medium of 3 T3-L1 cells under treatment with AA-24-a. Protein and mRNA expression and phosphorylation levels of the main lipases and kinases involved in lipolysis regulation were determined by quantitative polymerase chain reaction and western blotting. Specific inhibitors of protein kinase A (PKA; H89) and extracellular signal-regulated kinase (ERK; PD98059), which are key enzymes in relevant signaling pathways, were used to examine their roles in AA-24-a-stimulated lipolysis. Results AA-24-a significantly stimulated neutral lipolysis in fully differentiated adipocytes. To determine the underlying mechanism, we assessed the changes in mRNA and protein levels of key lipolysis-related genes in the presence or absence of H89 and PD98059. Both inhibitors reduced AA-24-a-induced lipolysis. Moreover, pretreatment with H89 attenuated AA-24-a-induced phosphorylation of hormone-sensitive lipase at Ser660, while pretreatment with PD98059 attenuated AA-24-a-induced downregulation of peroxisome proliferator-activated receptor-γ and perilipin A. Conclusions Our results indicate that AA-24-a promoted neutral lipolysis in 3 T3-L1 adipocytes by activating PKA-mediated phosphorylation of hormone-sensitive lipase and ERK- mediated downregulation of expression of perilipin A.

Potential lipolytic regulators derived from natural products as effective approaches to treat obesity

“…Terpenoids comprise five-carbon isoprene units and have diverse effects on obesity and its associated metabolic diseases. Triterpenoids include 18β-glycyrrhetinic acid (18β-GA) ( 88 ), ursolic acid ( 89 ), acetyl-keto-β-boswellic acid (AKBA) ( 90 ), alisol A 24-acetate (AA-24-a) ( 91 ), celastrol ( 92 ), and betulinic acid ( 93 ). All of these reduce neutral lipids in the cytosol and increase FFA release.…”

Pharmacological Properties and Molecular Targets of Alisol Triterpenoids from Alismatis Rhizoma

“…The related compound, Ali-A 24-acetate, is also able to reduce liver lipid deposition in hyperlipidemic mice via a blockade of AMPK activation to promote glucose metabolism and by promoting expression of ATP binding cassette transporters ABCG1 and ABCA1 [ 60 , 61 ]. The compound stimulates lipolysis of adipocytes by activating protein kinase A (PKA)-mediated phosphorylation of hormone-sensitive lipase [ 62 ]. These observations make Ali-A 24-acetate and Ali-B 23-acetate good candidates for the treatment of nonalcoholic fatty liver disease and its comorbidities [ 63 ].…”

Application of herbs and active ingredients ameliorate non-alcoholic fatty liver disease under the guidance of traditional Chinese medicine

“…[Alismataceae]. AA-24-a can improve the abnormal accumulation of lipids in the liver by regulating a variety of molecular mechanisms, such as improving liver lipid deposition through ABCA1/ABCG1 pathway in Apoe−/− mice model ( 53 ), binding to HMG-COA reductase ( 54 ), activating PKA-mediated hormone-sensitive lipase phosphorylation and down-regulating perilipin A in vivo and in vitro ( 55 ). Alisol B 23-acetate (AB-23-a), a natural triterpenoid, can induce mobilization of internally stored calcium, leading to autophagy by activating the CAMKK-AMPK- pathway in vitro ( 56 ), to improve abnormal lipid metabolism and reduce cytotoxicity.…”

“…UDCA treatment suppressed the activation of AKT, mTOR, and CRTC2 and the expression of nSREBP-1 in vitro ( 76 ). Additionally, it has been reported that UDCA administration promotes autophagy by activating the AMPK pathway to inhibit apoptosis ( 55 ).…”