Loss of mtch2 function impairs early development of liver, intestine and visceral adipocytes in zebrafish larvae

Abstract

The mitochondrial carrier homologue 2 (MTCH2) has been shown to be essential for embryogenesis in mice, and variants in the MTCH2 locus have been linked to obesity in humans. Here, we investigated the importance of mtch2 for embryogenesis and adipocyte formation in zebrafish in vivo. We show that mtch2 is conserved in zebrafish and broadly expressed during embryogenesis. Knock-down of mtch2 results in impaired development of liver and intestine, and is associated with a reduced number of adipocytes and impaired postembryonic growth. The findings indicate an essential role for mtch2 during organ development and adipogenesis in vivo.

Computational analyses of obesity associated loci generated by genome-wide association studies

“…MTCH2 is a conserved regulator of lipid homeostasis. Knockdown of MTCH2/mtch2 reduced lipid accumulation (in adipocyte-like cells, C. elegans and mice) [ 15 ] and number of adipocytes (in zebrafish) [ 16 ], while overexpression of MTCH2 increased fat accumulation (in adipocyte-like cells, C. elegans and mice) [ 15 , 17 ]. Loss of muscle MTCH2 protected mice from diet-induced obesity and hyperinsulinemia and increased energy expenditure [ 18 ].…”

MTCH2 is a conserved regulator of lipid homeostasis

“…Studies modulating MTCH2 levels in mice, mammalian cells, and zebra fish have now described a functional role for this gene in adiposity . MTCH2 deletion in skeletal muscle is sufficient to protect mice from weight gain on a high‐fat diet and to increase mitochondrial mass and metabolism .…”

“…Conversely, whole‐body MTCH2 overexpression was found to cause fatty liver and fatty kidney . Knockout of the zebra fish MTCH2 homolog using morpholinos confirmed its role in the early development of liver, intestine, and visceral adipocytes . The exact molecular mechanism of MTCH2 action in lipid regulation, however, remains largely unknown.…”

Der Zebrafisch als in vivo-Modellsystem für Adipositas und assoziierte Erkrankungen

“…Dies stellt einen Unterschied zu anderen verwendeten Modellorganismen dar, im Speziellen Drosophila melanogaster und Caenorhabditis elegans dar, bei denen Lipide in sogenannten fat bodies, die nicht-spezialisierte Zellen mit unterschiedlichen Funktionen sind, gespeichert werden (17). (21). Darüber hinaus haben in den letzten Jahren mehrere weitere Studien den Zebrafisch aufgrund seiner Vorteile der einfachen Haltung und schnellen Entwicklung sowie Transparenz in frühen Entwicklungsstadien für in vivo-Analysen zur physiologischen Relevanz von neuen Regulatoren der Adipogenese genutzt.…”