2月20日，日本和英国科研人员的一项新研究显示，实验动物细胞内存在一种与肥胖有关的基因，如果该基因发生变异，会进一步提高摄取高脂肪食物所面临的肥胖风险。
日本京都大学和英国伦敦帝国学院等机构组成的联合研究小组20日在英国学术期刊《自然》网络版上报告说，他们发现基因GPR120编码合成的蛋白质能察觉进入机体的脂肪，进而抑制食欲。如果这种基因出现变异，肌体燃烧脂肪的能力就会降低。
研究人员培养出上述基因不发挥作用的小鼠，喂它们吃脂肪比例达到60％的高脂肪食物，如此饲养16周后，将它们与吃同样高脂肪食物的正常小鼠进行比较。结果显示，前者体重增加了15％，包括内脏脂肪在内的脂肪总量增长了约1倍，并且出现脂肪肝和糖尿病症状。而对照组的正常小鼠体重增加不到4％。
此外，如果喂食脂肪比例只有约10％的食物，则GPR120基因不发挥作用的小鼠和正常小鼠的体重变化几乎没有差别。研究小组认为，这说明这种基因与食物原因导致的肥胖具有密切关系。
研究小组还分析了英国、法国等欧洲国家经常进食高脂肪食物的约6900名肥胖者和7650名健康者的GPR120基因。结果发现，肥胖者中GPR120基因出现变异导致该基因功能下降的比例是2.4％，而健康者当中该基因发生变异的比例约为1.3％。
研究小组成员、京都大学教授辻本豪三指出：“西方高脂肪饮食习惯和基因功能下降的叠加效应将提高肥胖和糖尿病风险，今后有望依靠诊断GPR120基因，对代谢综合征进行预防和治疗。”(生物谷Bioon.com)
doi:10.1038/nature10798
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Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human
Atsuhiko Ichimura,Akira Hirasawa, Odile Poulain-Godefroy,Amélie Bonnefond, Takafumi Hara,Loc Yengo Ikuo Kimura,Audrey Leloire, Ning Liu, Keiko Iida,1 Hélène Choquet, Philippe Besnard, Cécile Lecoeur,Sidonie Vivequin,Kumiko Ayukawa Masato Takeuchi,Kentaro Ozawa,1 Maithé Tauber, Claudio Maffeis, Anita Morandi,Raffaella Buzzetti,Paul Elliott,Anneli Pouta, Marjo-Riitta Jarvelin, Antje Krner,Wieland Kiess, Marie Pigeyre,Roberto Caiazzo,Wim Van Hul, Luc Van Gaal,Fritz Horber,Beverley Balkau，Claire Lévy-Marchal, Konstantinos Rouskas,Anastasia Kouvatsi,Johannes Hebebrand,Anke Hinney, Andre Scherag, Fran?ois Pattou, David Meyre, Taka-aki Koshimizu,Isabelle Wolowczuk,Gozoh Tsujimoto1 & Philippe Frogue et al.
Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes1, 2, 3, 4. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases3, 5, 6, 7, 8, 9, 10, 11, 12, 13. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference5, 6, 14, 15, 16. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.
