title: MicroRNA-192* impairs adipocyte triglyceride storage.
abstract: We investigated the expression of miR-192* (miR-192-3p) in the visceral adipose tissue (VAT) of obese subjects and its function in cultured human adipocytes. This miRNA is a 3' arm derived from the same pre-miRNA as miR-192 (miR-192-5p) implicated in type 2 diabetes, liver disease and cancers, and is predicted to target key genes in lipid metabolism. In morbidly obese subjects undergoing bariatric surgery preceded by a very low calorie diet, miR-192* in VAT correlated negatively (r=-0.387; p=0.046) with serum triglyceride (TG) and positively with high-density lipoprotein (HDL) concentration (r=0.396; p=0.041). In a less obese patient cohort, the miRNA correlated negatively with the body mass index (r=-0.537; p=0.026). To characterize the function of miR-192*, we overexpressed it in cultured adipocytes and analyzed the expression of adipogenic differentiation markers as well as cellular TG content. Reduced TG and expression of the adipocyte marker proteins aP2 (adipocyte protein 2) and perilipin 1 were observed. The function of miR-192* was further investigated by transcriptomic profiling of adipocytes expressing this miRNA, revealing impacts on key lipogenic genes. A number of the mRNA alterations were validated by qPCR. Western analysis confirmed a marked reduction of the lipogenic enzyme SCD (stearoyl coenzyme A desaturase-1), the fatty aldehyde dehydrogenase ALDH3A2 (aldehyde dehydrogenase 3 family member A2) and the high-density lipoprotein receptor SCARB1 (scavenger receptor B, type I). SCD and ALDH3A2 were demonstrated to be direct targets of miR-192*. To conclude, the present data identify miR-192* as a novel controller of adipocyte differentiation and lipid homeostasis.
authors.affiliation: Minerva Foundation Institute for Medical Research, Biomedicum 2U, FI-00290 Helsinki, Finland.
authors.forename: Raghavendra
authors.initials: R
authors.lastname: Mysore
authors.affiliation: Minerva Foundation Institute for Medical Research, Biomedicum 2U, FI-00290 Helsinki, Finland.
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Minerva Foundation Institute for Medical Research, Biomedicum 2U, FI-00290 Helsinki, Finland; Department of Medicine, University of Helsinki, FI-00014 Finland.
authors.forename: Sanja
authors.initials: S
authors.lastname: Sädevirta
authors.affiliation: University of Helsinki and Helsinki University Hospital, Obstetrics and Gynecology, FI-00029 HUS, Helsinki, Finland; Folkhälsan Research Center, FI-00290 Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Savolainen-Peltonen
authors.affiliation: Minerva Foundation Institute for Medical Research, Biomedicum 2U, FI-00290 Helsinki, Finland.
authors.forename: P A
authors.initials: PA
authors.lastname: Nidhina Haridas
authors.affiliation: Minerva Foundation Institute for Medical Research, Biomedicum 2U, FI-00290 Helsinki, Finland; National Institute for Health and Welfare/Public Health Genomics Unit, Biomedicum, FI-00290 Helsinki, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Soronen
authors.affiliation: Department of Surgery, Helsinki University Central Hospital, FI-000290 HUS, Helsinki, Finland.
authors.forename: Marja
authors.initials: M
authors.lastname: Leivonen
authors.affiliation: National Institute for Health and Welfare/Public Health Genomics Unit, Biomedicum, FI-00290 Helsinki, Finland; Institute for Molecular Medicine Finland FIMM, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Antti-Pekka
authors.initials: AP
authors.lastname: Sarin
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D-89075 Ulm, Germany.
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D-89075 Ulm, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.affiliation: Minerva Foundation Institute for Medical Research, Biomedicum 2U, FI-00290 Helsinki, Finland; Department of Medicine, University of Helsinki, FI-00014 Finland.
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
authors.affiliation: Minerva Foundation Institute for Medical Research, Biomedicum 2U, FI-00290 Helsinki, Finland; Department of Anatomy, Faculty of Medicine, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: vesa.olkkonen@helsinki.fi.
authors.forename: Vesa M
authors.initials: VM
authors.lastname: Olkkonen
mesh_terms: D052438:Adipocytes, White / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics; D000328:Adult; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D008075:Lipoproteins, HDL; C546783:MIRN192 microRNA, human; D035683:MicroRNAs; C000602978:PLIN1 protein, human; D000070778:Perilipin-1; D010750:Phosphoproteins; D012333:RNA, Messenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase
keywords: Adipogenesis; Obesity; SGBS; Transcriptome; miR-192-3p