ARS | Publication request: The Association of Snp276g>t at Adiponectin Gene with Circulating Adiponectin and Insulin Resistance in Response to Mild Weight Loss

Submitted to: International Journal of Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 27, 2006
Publication Date: April 11, 2006
Publisher's URL: http://www.nature.com/ijo/journal/v30/n12/abs/0803338a.html
Citation: Shin, M., Jang, Y., Koh, S., Chae, J., Kim, O., Lee, J., Ordovas, J.M., Lee, J. 2006. The association of SNP276G>T at adiponectin gene with circulating adiponectin and insulin resistance in response to mild weight loss. International Journal of Obesity. 30: 1702¿1708.

Interpretive Summary: Obesity has been identified ¿one of today¿s most blatantly visible ¿ yet most neglected ¿ public health problems.¿ This rising epidemic of overweight and obesity has been called by some as ¿globesity¿ to clearly reflect that is a global problem and that, unless action is taken, billions will suffer from debilitating conditions associated with this disorder. Overeating and sedentary lifestyle are major environmental factors determining the current globesity; however, genetic factors are also important to predispose some people to obesity. Moreover, genetic factors may also affect the development of obesity related disease such as the Type II diabetes. Therefore, it would be very important to identify genetic markers that could help to personalize diet therapies aimed to maintain or achieve ideal body weight and prevent obesity related diseases. We have examined the gene for adiponectin, a protein with insulin-sensitizing and anti-inflammatory functions, in relation to circulating adiponectin and insulin resistance in response to mild weight loss. One form of the gene showed significantly higher level of circulating adiponectin response and lower insulin resistance than the others during the mild weight loss process, suggesting that carriers of this gene form may benefit more from a weight loss program in terms of preventing certain obesity related diseases such as diabetes.

Technical Abstract: The purpose of this study was to determine whether common single nucleotide polymorphisms (SNPs) at the adiponectin (ADIPOQ) locus influence changes in circulating adiponectin and the features of insulin resistance in response to a weight loss intervention. 294 nondiabetic/overweight-obese Koreans participated in a clinical intervention study lasting 12 weeks involving a caloric reduction of -300kcal/day. Plasma adiponectin, blood lipids, glucose and insulin concentrations were measured at baseline and after weight loss. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR) derived from fasting glucose and insulin concentrations. We genotyped for 3 SNPs 45T>G, 276G>T and -11377C>G. At baseline, HOMA-IR was significantly higher in GG homozygotes than in carriers of the T allele at SNP 276G>T of the adiponectin gene (p<0.05). With regard to SNP45T>G and SNP-11377C>G, we did not find any genotype related differences in baseline levels of HOMA-IR and adiponectin. In the 45/276 haplotype test, homozygous for the TG haplotype had significantly lower concentrations of plasma adiponectin (p<0.05). After the 12-week weight loss intervention, the significant decreased in HOMA-IR (p<0.001) and increases in adiponectin (p<0.01) were observed in GG homozygotes at SNP276, which were not shown in carriers of the T allele. Furthermore, there was a significant difference in the decreases in HOMA-IR between the GG homozygotes and carriers of the T allele at SNP276 (p<0.05). Regarding SNP45T>G and SNP-11377C>G, there was no association between SNP45T>G and SNP-11377C>G and decreases in HOMA-IR. In the 45/276 haplotype test, there was a significant difference in changes of adiponectin levels among those with different haplotype combinations (p<0.05). The SNP276G>T of the ADIPOQ gene is associated with different responses of circulating adiponectin and insulin resistance to mild weight loss in overweight-obese subjects.