Effects of arecoline on adipogenesis, lipolysis, and glucose uptake of adipocytes-A possible role of betel-quid chewing in metabolic syndrome.

Abstract

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.

• Authors: Hsin-Fen Hsu, Tsui-Chun Tsou, How-Ran Chao, Cherng-Gueih Shy, Ya-Ting Kuo, Feng-Yuan Tsai, Szu-Ching Yeh, Ying-Chin Ko
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 245 Issue 3 Pg. 370-7 (Jun 15 2010) ISSN: 1096-0333 [Electronic] United States
• PMID: 20406654 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Insulin
• Triglycerides
• Arecoline
• Adenylyl Cyclases
• Glucose
• Glycerol

Topics

• 3T3-L1 Cells
• Adenylyl Cyclases (metabolism)
• Adipocytes (drug effects, metabolism)
• Adipogenesis (drug effects, genetics)
• Adult
• Aged
• Animals
• Areca (adverse effects)
• Arecoline (toxicity)
• Biological Transport
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Female
• Gene Expression Regulation (drug effects)
• Glucose (metabolism)
• Glycerol (metabolism)
• Humans
• Hyperlipidemias (blood, etiology)
• Insulin (metabolism)
• Lipolysis (drug effects)
• Male
• Mastication
• Metabolic Syndrome (blood, etiology)
• Mice
• Middle Aged
• Nuts
• Time Factors
• Triglycerides (blood)