Inhibitory effects of caffeine and its metabolites on intracellular lipid accumulation in murine 3T3-L1 adipocytes.
To understand the mechanisms of the anti-obesity effects of dietary caffeine, the effects of caffeine and its metabolites on adipocyte differentiation and insulin-stimulated glucose uptake in murine 3T3-L1 adipocytes were investigated. Caffeine did not inhibit the differentiation of 3T3-L1 pre-adipocytes to mature adipocytes, but it did suppress the intracellular lipid accumulation after complete differentiation in a dose-dependent manner (0.125-1.0 mM). This effect was also observed in 1,3,7-trimethyluric acid- 3,7-dimethyluric acid- and 5-acetylamino-6-formylamino-3-methyluracil-treated cells. Caffeine also inhibited insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes in a dose-dependent manner. Treatment with theophylline, paraxanthine, 1-methylxanthine (MX), 3-MX, or 7-MX also inhibited glucose uptake in differentiated adipocytes. These results suggest that the anti-obesity activity of dietary caffeine is due to the additive and/or synergistic inhibitory effects of caffeine and its metabolites on intracellular lipid accumulation and that caffeine does not affect adipocyte differentiation.
Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo, Japan.
Hideo
H
Nakabayashi
Takashi
T
Hashimoto
Hitoshi
H
Ashida
Shin
S
Nishiumi
Kazuki
K
Kanazawa
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D013806:Theophylline / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology; D014527:Uric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D019440:Anti-Obesity Agents; D007328:Insulin; D014970:Xanthines; D014527:Uric Acid; C008514:methylxanthine; D002110:Caffeine; C039222:1,3,7-trimethyluric acid; D014498:Uracil; C055991:3-methyluracil; C053085:1-methylxanthine; C036692:5-acetylamino-6-formylamino-3-methyluracil; D013806:Theophylline; D005947:Glucose; C066065:3,7-dimethyluric acid