Effects of arecoline on adipogenesis, lipolysis, and glucose uptake of adipocytes-A possible role of betel-quid chewing in metabolic syndrome.
To investigate the possible involvement of betel-quid chewing in adipocyte dysfunction, we determined the effects of arecoline, a major alkaloid in areca nuts, on adipogenic differentiation (adipogenesis), lipolysis, and glucose uptake by fat cells. Using mouse 3T3-L1 preadipocytes, we showed that arecoline inhibited adipogenesis as determined by oil droplet formation and adipogenic marker gene expression. The effects of arecoline on lipolysis of differentiated 3T3-L1 adipocytes were determined by the glycerol release assay, indicating that arecoline induced lipolysis in an adenylyl cyclase-dependent manner. The diabetogenic effects of arecoline on differentiated 3T3-L1 adipocytes were evaluated by the glucose uptake assay, revealing that > or = 300 microM arecoline significantly attenuated insulin-induced glucose uptake; however, no marked effect on basal glucose uptake was detected. Moreover, using 94 subjects that were randomly selected from a health check-up, we determined the association of betel-quid chewing with hyperlipidemia and its related risk factors. Hyperlipidemia frequency and serum triglyceride levels of betel-quid chewers were significantly higher than those of non-betel-quid chewers. In this study, we demonstrated that arecoline inhibits adipogenic differentiation, induces adenylyl cyclase-dependent lipolysis, and interferes with insulin-induced glucose uptake. Arecoline-induced fat cell dysfunction may lead to hyperlipidemia and hyperglycemia/insulin-resistance. These findings provide the first in vitro evidence of betel-quid chewing modulation of adipose cell metabolism that could contribute to the explanation of the association of this habit with metabolic syndrome disorders.
Hsu
Hsin-Fen
HF
Laboratory of Molecular Toxicology, Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Tsou
Tsui-Chun
TC
Chao
How-Ran
HR
Shy
Cherng-Gueih
CG
Kuo
Ya-Ting
YT
Tsai
Feng-Yuan
FY
Yeh
Szu-Ching
SC
Ko
Ying-Chin
YC
D041721:3T3-L1 Cells; D000262:Adenylyl Cyclases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000328:Adult; D000368:Aged; D000818:Animals; D001114:Areca / Q000009:adverse effects*; D001115:Arecoline / Q000633:toxicity*; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000209:etiology; D007328:Insulin / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008409:Mastication; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology*; D051379:Mice; D008875:Middle Aged; D009754:Nuts; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D007328:Insulin; D014280:Triglycerides; D001115:Arecoline; D000262:Adenylyl Cyclases; D005947:Glucose; D005990:Glycerol