Phan Jack, Reue Karen
Department of Human Genetics, David Geffen School of Medicine and Molecular Biology Institute, University of California, Los Angeles 90073, USA.
Cell Metab. 2005 Jan;1(1):73-83. doi: 10.1016/j.cmet.2004.12.002.
Lipodystrophy and obesity represent extreme and opposite ends of the adiposity spectrum and have typically been attributed to alterations in the expression or function of distinct sets of genes. We previously demonstrated that lipin deficiency impairs adipocyte differentiation and causes lipodystrophy in the mouse. Using two different tissue-specific lipin transgenic mouse strains, we now demonstrate that enhanced lipin expression in either adipose tissue or skeletal muscle promotes obesity. This occurs through diverse mechanisms in the two tissues, with lipin levels in adipose tissue influencing the fat storage capacity of the adipocyte, and lipin levels in skeletal muscle acting as a determinant of whole-body energy expenditure and fat utilization. Thus, variations in lipin levels alone are sufficient to induce extreme states of adiposity and may represent a mechanism by which adipose tissue and skeletal muscle modulate fat mass and energy balance.
脂肪营养不良和肥胖代表了肥胖谱系的两个极端且相反的端点，通常被认为是由不同基因集的表达或功能改变所致。我们之前证明，脂素缺乏会损害脂肪细胞分化，并在小鼠中导致脂肪营养不良。现在，我们利用两种不同的组织特异性脂素转基因小鼠品系证明，脂肪组织或骨骼肌中脂素表达增强会促进肥胖。这在两种组织中通过不同机制发生，脂肪组织中的脂素水平影响脂肪细胞的脂肪储存能力，而骨骼肌中的脂素水平则作为全身能量消耗和脂肪利用的决定因素。因此，仅脂素水平的变化就足以诱发肥胖的极端状态，并且可能代表了脂肪组织和骨骼肌调节脂肪量和能量平衡的一种机制。
