title: MicroRNA profiling links miR-378 to enhanced adipocyte lipolysis in human cancer cachexia.
abstract: Cancer cachexia is associated with pronounced adipose tissue loss due to, at least in part, increased fat cell lipolysis. MicroRNAs (miRNAs) have recently been implicated in controlling several aspects of adipocyte function. To gain insight into the possible impact of miRNAs on adipose lipolysis in cancer cachexia, global miRNA expression was explored in abdominal subcutaneous adipose tissue from gastrointestinal cancer patients with (n = 10) or without (n = 11) cachexia. Effects of miRNA overexpression or inhibition on lipolysis were determined in human in vitro differentiated adipocytes. Out of 116 miRNAs present in adipose tissue, five displayed distinct cachexia-associated expression according to both microarray and RT-qPCR. Four (miR-483-5p/-23a/-744/-99b) were downregulated, whereas one (miR-378) was significantly upregulated in cachexia. Adipose expression of miR-378 associated strongly and positively with catecholamine-stimulated lipolysis in adipocytes. This correlation is most probably causal because overexpression of miR-378 in human adipocytes increased catecholamine-stimulated lipolysis. In addition, inhibition of miR-378 expression attenuated stimulated lipolysis and reduced the expression of LIPE, PLIN1, and PNPLA2, a set of genes encoding key lipolytic regulators. Taken together, increased miR-378 expression could play an etiological role in cancer cachexia-associated adipose tissue loss via effects on adipocyte lipolysis.
authors: Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden;
authors: Agné
authors: A
authors: Kulyté
authors: Silvia
authors: S
authors: Lorente-Cebrián
authors: Hui
authors: H
authors: Gao
authors: Niklas
authors: N
authors: Mejhert
authors: Thorhallur
authors: T
authors: Agustsson
authors: Peter
authors: P
authors: Arner
authors: Mikael
authors: M
authors: Rydén
authors: Ingrid
authors: I
authors: Dahlman
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D000368:Aged; D002100:Cachexia / Q000209:etiology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008066:Lipolysis / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D046228:Microarray Analysis; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism
chemical_list: C526012:MIRN378 microRNA, human; D035683:MicroRNAs
keywords: adipocytes; cancer cachexia; lipolysis; miR-378; miRNA expression