Vaicik Marcella K, Blagajcevic Alen, Ye Honggang, Morse Mallory C, Yang Feipeng, Goddi Anna, Brey Eric M, Cohen Ronald N
Research Service, Edward Hines Jr. VA Hospital, Hines, Illinois.
Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois.
Endocrinology. 2018 Jan 1;159(1):356-367. doi: 10.1210/en.2017-00186.
Laminin α4 (LAMA4) is located in the extracellular basement membrane that surrounds each individual adipocyte. Here we show that LAMA4 null (Lama4-/-) mice exhibit significantly higher energy expenditure (EE) relative to wild-type (WT) mice at room temperature and when exposed to a cold challenge, despite similar levels of food intake and locomotor activity. The Lama4-/- mice are resistant to age- and diet-induced obesity. Expression of uncoupling protein 1 is higher in subcutaneous white adipose tissue of Lama4-/- mice relative to WT animals on either a chow diet or a high-fat diet. In contrast, uncoupling protein 1 expression was not increased in brown adipose tissue. Lama4-/- mice exhibit significantly improved insulin sensitivity compared with WT mice, suggesting improved metabolic function. Overall, these data provide critical evidence for a role of the basement membrane in EE, weight gain, and systemic insulin sensitivity.
层粘连蛋白α4（LAMA4）位于围绕每个脂肪细胞的细胞外基底膜中。我们在此表明，层粘连蛋白α4基因敲除（Lama4-/-）小鼠在室温下以及受到冷刺激时，相对于野生型（WT）小鼠表现出显著更高的能量消耗（EE），尽管它们的食物摄入量和运动活动水平相似。Lama4-/-小鼠对年龄和饮食诱导的肥胖具有抗性。无论在正常饮食还是高脂饮食条件下，Lama4-/-小鼠皮下白色脂肪组织中解偶联蛋白1的表达均高于野生型动物。相比之下，棕色脂肪组织中解偶联蛋白1的表达并未增加。与WT小鼠相比，Lama4-/-小鼠表现出显著改善的胰岛素敏感性，提示代谢功能得到改善。总体而言，这些数据为基底膜在能量消耗、体重增加和全身胰岛素敏感性方面的作用提供了关键证据。
