Viguerie N, Vidal H, Arner P, Holst C, Verdich C, Avizou S, Astrup A, Saris W H M, Macdonald I A, Klimcakova E, Clément K, Martinez A, Hoffstedt J, Sørensen T I A, Langin D
Obesity Research Unit of the French Institute of Health and Medical Research U586, Louis Bugnard Institute and Clinical Investigation Centre, Toulouse University Hospitals, Paul Sabatier University, Toulouse, France.
Diabetologia. 2005 Jan;48(1):123-31. doi: 10.1007/s00125-004-1618-x. Epub 2004 Dec 29.
AIMS/HYPOTHESIS: Adaptation to energy restriction is associated with changes in gene expression in adipose tissue. However, it is unknown to what extent these changes are dependent on the energy restriction as such or on the macronutrient composition of the diet.
We determined the levels of transcripts for 38 genes that are expressed in adipose tissue and encode transcription factors, enzymes, transporters and receptors known to play critical roles in the regulation of adipogenesis, mitochondrial respiration, and lipid and carbohydrate metabolism. Two groups of 25 obese subjects following 10-week hypocaloric diet programmes with either 20-25 or 40-45% of total energy derived from fat were investigated. Levels of mRNA were measured by performing real-time RT-PCR on subcutaneous fat samples obtained from the subjects before and after the diets.
The two groups of subjects lost 7 kg over the duration of the diets. Ten genes were regulated by energy restriction; however, none of the genes showed a significantly different response to the diets. Levels of peroxisome proliferator-activated receptor gamma co-activator 1alpha mRNA were increased, while the expression of the genes encoding leptin, osteonectin, phosphodiesterase 3B, hormone-sensitive lipase, receptor A for natriuretic peptide, fatty acid translocase, lipoprotein lipase, uncoupling protein 2 and peroxisome proliferator-activated receptor gamma was decreased. Clustering analysis revealed new potential coregulation of genes. For example, the expression of the genes encoding the adiponectin receptors may be regulated by liver X receptor alpha.
CONCLUSIONS/INTERPRETATION: In accordance with the comparable loss of fat mass produced by the two diets, this study shows that energy restriction and/or weight loss rather than the ratio of fat: carbohydrate in a low-energy diet is of importance in modifying the expression of genes in the human adipose tissue.
目的/假设：能量限制适应与脂肪组织中的基因表达变化相关。然而，这些变化在多大程度上依赖于能量限制本身或饮食中的常量营养素组成尚不清楚。
我们测定了38个在脂肪组织中表达的基因的转录本水平，这些基因编码已知在脂肪生成、线粒体呼吸以及脂质和碳水化合物代谢调节中起关键作用的转录因子、酶、转运蛋白和受体。对两组各25名肥胖受试者进行了研究，他们遵循为期10周的低热量饮食计划，饮食中脂肪提供的能量分别占总能量的20 - 25%或40 - 45%。通过对受试者饮食前后获取的皮下脂肪样本进行实时逆转录聚合酶链反应来测量mRNA水平。
两组受试者在饮食期间体重减轻了7千克。10个基因受能量限制调节；然而，没有一个基因对两种饮食表现出显著不同的反应。过氧化物酶体增殖物激活受体γ共激活因子1α mRNA水平升高，而编码瘦素、骨连接蛋白、磷酸二酯酶3B、激素敏感性脂肪酶、利钠肽受体A、脂肪酸转运蛋白、脂蛋白脂肪酶、解偶联蛋白2和过氧化物酶体增殖物激活受体γ的基因表达降低。聚类分析揭示了基因新的潜在共调节作用。例如，编码脂联素受体的基因表达可能受肝X受体α调节。
结论/解读：鉴于两种饮食导致的脂肪量减少相当，本研究表明，在改变人体脂肪组织中的基因表达方面，能量限制和/或体重减轻而非低能量饮食中脂肪与碳水化合物的比例更为重要。
