Functional polymorphism of IL-1 alpha and its potential role in obesity in humans and mice.
Proinflammatory cytokines secreted from adipose tissue contribute to the morbidity associated with obesity. IL-1α is one of the proinflammatory cytokines; however, it has not been clarified whether IL-1α may also cause obesity. In this study, we investigated whether polymorphisms in IL-1α contribute to human obesity. A total of 260 obese subjects were genotyped for IL-1α C-889T (rs1800587) and IL-1α G+4845T (rs17561). Analyses of genotype distributions revealed that both IL-1α polymorphisms C-889T (rs1800587) and G+4845T (rs17561) were associated with an increase in body mass index in obese healthy women. In addition, the effect of rs1800587 on the transcriptional activity of IL-1α was explored in pre-adipocyte 3T3-L1 cells. Significant difference was found between the rs1800587 polymorphism in the regulatory region of the IL-1α gene and transcriptional activity. We extended these observations in vivo to a high-fat diet-induced obese mouse model and in vitro to pre-adipocyte 3T3-L1 cells. IL-1α levels were dramatically augmented in obese mice, and triglyceride was increased 12 hours after IL-1α injection. Taken together, IL-1α treatment regulated the differentiation of preadipocytes. IL-1α C-889T (rs1800587) is a functional polymorphism of IL-1α associated with obesity. IL-1α may have a critical function in the development of obesity.
Department of Pharmacology, College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea. jyum@khu.ac.kr
Jae-Young
JY
Um
Hong-Kun
HK
Rim
Su-Jin
SJ
Kim
Hye-Lin
HL
Kim
Seung-Heon
SH
Hong
D041721:3T3-L1 Cells; D000818:Animals; D001483:Base Sequence; D015992:Body Mass Index; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology
D017931:DNA Primers; D053582:Interleukin-1alpha