Viguerie N, Poitou C, Cancello R, Stich V, Clément K, Langin D
Unité de Recherches sur les Obésités Inserm UPS U586, Institut Louis Bugnard, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France.
Biochimie. 2005 Jan;87(1):117-23. doi: 10.1016/j.biochi.2004.12.011.
Caloric restriction still remains the most efficient way to promote weight loss. Deciphering the molecular basis of adaptation to energy restriction is critical for the tailoring of new therapeutic strategies. This review focuses on the recent input of gene profiling on adipose tissue in obesity pathogenesis and on the new insights on adaptations occurring during very low caloric diet (VLCD) in humans. Hypocaloric diets improve a wide range of metabolic parameters including lipolytic efficiency, insulin sensitivity, and inflammatory profile. In the subcutaneous white adipose tissue (scWAT) the VLCD induced a decrease in the mRNA levels for the antilipolytic alpha2-adrenergic receptor associated with changes in catecholamine-induced adipocyte lipolytic capacity. The improvement in insulin sensitivity was not associated with a change in subcutaneous adipose tissue adiponectin gene expression or in its plasma level, suggesting that adiponectin is not involved in the regulation of VLCD-induced improvement of insulin sensitivity and that there is a small contribution of subcutaneous adipose tissue to plasma adiponectin levels. Pangenomic microarray studies in human scWAT revealed that a panel of inflammatory markers and acute phase reactants were over expressed in obese compared to lean subjects. Caloric restriction improved the inflammatory profile of obese subjects through a decrease of pro-inflammatory factors and an increase of anti-inflammatory molecules. These genes were mostly expressed in the stroma vascular fraction of the adipose tissue. Specific cell-type isolation and immunohistochemistry demonstrated that monocyte/macrophage lineage cells were responsible for the expression of both mRNA and protein inflammatory markers. The acute phase proteins serum amyloid A was highly expressed in mature adipocytes from obese subjects. Caloric restriction decreased both serum amyloid mRNA and circulating levels. Obesity now clearly appears as chronic low-grade inflammation state. Modulation of the inflammatory pathways may represent new therapeutic targets for the treatment of obesity-related complications.
热量限制仍然是促进体重减轻的最有效方法。解读能量限制适应的分子基础对于制定新的治疗策略至关重要。本综述重点关注基因谱分析在肥胖发病机制中对脂肪组织的最新研究成果，以及人类极低热量饮食（VLCD）期间发生的适应性变化的新见解。低热量饮食可改善广泛的代谢参数，包括脂肪分解效率、胰岛素敏感性和炎症特征。在皮下白色脂肪组织（scWAT）中，VLCD导致抗脂肪分解的α2-肾上腺素能受体mRNA水平降低，这与儿茶酚胺诱导的脂肪细胞脂肪分解能力的变化有关。胰岛素敏感性的改善与皮下脂肪组织脂联素基因表达或其血浆水平的变化无关，这表明脂联素不参与VLCD诱导的胰岛素敏感性改善的调节，且皮下脂肪组织对血浆脂联素水平的贡献较小。对人类scWAT的全基因组微阵列研究表明，与瘦人相比，一组炎症标志物和急性期反应物在肥胖者中过度表达。热量限制通过降低促炎因子和增加抗炎分子来改善肥胖者的炎症特征。这些基因大多在脂肪组织的基质血管部分表达。特定细胞类型的分离和免疫组织化学表明，单核细胞/巨噬细胞谱系细胞负责mRNA和蛋白质炎症标志物的表达。急性期蛋白血清淀粉样蛋白A在肥胖受试者的成熟脂肪细胞中高度表达。热量限制降低了血清淀粉样蛋白mRNA和循环水平。肥胖现在显然表现为慢性低度炎症状态。调节炎症途径可能代表治疗肥胖相关并发症的新治疗靶点。
