生物
安普克
细胞生物学
PRDM16
内分泌学
白色脂肪组织
内科学
脂肪细胞
下调和上调
脂肪组织
脂肪生成
蛋白激酶A
激酶
生物化学
医学
基因
作者
Anna Goddi,Alanis Carmona,Soo Young Park,Gökhan Dalgin,Maria A. Gonzalez Porras,Eric M. Brey,Ronald N. Cohen
出处
期刊:Endocrinology
[The Endocrine Society]
日期:2022-09-19
卷期号:163 (11)
被引量:1
标识
DOI:10.1210/endocr/bqac154
摘要
Abstract Laminin-α4 (LAMA4) is an extracellular matrix protein implicated in the regulation of adipocyte differentiation and function. Prior research describes a role for LAMA4 in modulating adipocyte thermogenesis and uncoupling protein-1 (UCP1) expression in white adipose; however, the mechanisms involved are poorly understood. Here, we describe that Lama4 knockout mice (Lama4−/−) exhibit heightened mitochondrial biogenesis and peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) expression in subcutaneous white adipose tissue (sWAT). Furthermore, the acute silencing of LAMA4 with small interfering RNA in primary murine adipocytes was sufficient to upregulate the expression of thermogenic markers UCP1 and PR domain containing 16 (PRDM16). Silencing also resulted in an upregulation of PGC1-α and adenosine 5′-monophosphate–activated protein kinase (AMPK)-α expression. Subsequently, we show that integrin-linked kinase (ILK) is downregulated in the sWAT of Lama4−/− mice, and its silencing in adipocytes similarly resulted in elevated expression of UCP1 and AMPKα. Last, we demonstrate that treatment of human induced pluripotent stem cell–derived thermogenic adipocytes with LAMA4 (LN411) inhibited the expression of thermogenic markers and AMPKα. Overall, our results indicate that LAMA4 negatively regulates a thermogenic phenotype and pathways involving mitochondrial biogenesis in adipocytes through the suppression of AMPKα.
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