miR-375 is cold exposure sensitive and drives thermogenesis in visceral adipose tissue derived stem cells

Seeliger, Claudine; Krauss, Tanja; Honecker, Julius; Mengel, Laura Aline; Buekens, Lise; Mesas-Fernández, Alberto; Skurk, Thomas; Claussnitzer, Melina; Hauner, Hans

doi:10.1038/s41598-022-13610-6

Cited by 10 publications

(9 citation statements)

References 73 publications

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“…Seeliger et al . 49 demonstrated that miR-375 knockdown during visceral preadipocyte differentiation upregulated the adipogenesis marker genes ADIPOQ and ADIPOR2 . Gezginci-Oktayoglu et al .…”

Section: Discussionmentioning

confidence: 99%

SNPs in microRNA seed region and impact of miR-375 in concurrent regulation of multiple lipid accumulation-related genes

Lee,

Hong,

Lee

et al. 2024

Sci Rep

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Bovine intramuscular fat (IMF), commonly referred to as marbling, is regulated by lipid metabolism, which includes adipogenesis, lipogenesis, glycerolipid synthesis, and lipolysis. In recent years, breeding researchers have identified single nucleotide polymorphisms (SNPs) as useful marker-assisted selection tools for improving marbling scores in national breeding programs. These included causal SNPs that induce phenotypic variation. MicroRNAs (miRNAs) are small highly conserved non-coding RNA molecules that bind to multiple non-coding regions. They are involved in post-transcriptional regulation. Multiple miRNAs may regulate a given target. Previously, three SNPs in the GPAM 3ʹ UTR and four miRNAs were identified through in silico assays. The aim of this study is to verify the binding ability of the four miRNAs to the SNPs within the 3ʹUTR of GPAM, and to identify the regulatory function of miR-375 in the expression of genes related to lipid metabolism in mammalian adipocytes. It was verified that the four miRNAs bind to the GPAM 3ʹUTR, and identified that the miR-375 sequence is highly conserved. Furthermore, it was founded that miR-375 upregulated the GPAM gene, C/EBPα, PPARγ and lipid metabolism-related genes and promoted lipid droplet accumulation in 3T3-L1 cells. In conclusion, these results suggest that miR-375 is a multifunctional regulator of multiple lipid metabolism-related genes and may aid in obesity research as a biomarker.

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Section: Discussionmentioning

confidence: 99%

SNPs in microRNA seed region and impact of miR-375 in concurrent regulation of multiple lipid accumulation-related genes

Lee,

Hong,

Lee

et al. 2024

Sci Rep

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“…Thereby, miR‐375, which has an anti‐oncogene activity, was suggested as a candidate tumour suppressor 43 . Recently, our group could identify a connection between circulating miR‐375 levels and response to cold exposure 44 . Furthermore, miR‐375 may drive thermogenesis in visceral adipose tissue derived stem cells.…”

Section: Discussionmentioning

confidence: 99%

“…43 Recently, our group could identify a connection between circulating miR-375 levels and response to cold exposure. 44 Furthermore, miR-375 may drive thermogenesis in visceral adipose tissue derived stem cells.…”

Section: Discussionmentioning

confidence: 99%

Specific miRNAs are associated with human cancer cachexia in an organ‐specific manner

Krauss

Heisz

Honecker

et al. 2023

J cachexia sarcopenia muscle

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Background Cancer cachexia (CCx) is a complex and multi-organ wasting syndrome characterized by substantial weight loss and poor prognosis. An improved understanding of the mechanisms involved in the onset and progression of cancer cachexia is essential. How microRNAs contribute to the clinical manifestation and progression of CCx remains elusive. The aim of this study was to identify specific miRNAs related to organ-specific CCx and explore their functional role in humans. Methods miRNA patterns in serum and in cachexia target organs (liver, muscle and adipose tissue) from weight stable (N ≤ 12) and cachectic patients (N ≤ 23) with gastrointestinal cancer were analysed. As a first step, a miRNA array (158 miRNAs) was performed in pooled serum samples. Identified miRNAs were validated in serum and corresponding tissue samples. Using in silico prediction, related genes were identified and evaluated. The findings were confirmed in vitro by siRNA knock-down experiments in human visceral preadipocytes and C2C12 myoblast cells and consecutive gene expression analyses. Results Validating the results of the array, a 2-fold down-regulation of miR-122-5p (P = 0.0396) and a 4.5-fold down-regulation of miR-194-5p (P < 0.0001) in serum of CCx patients in comparison with healthy controls were detected. Only miR-122-5p correlated with weight loss and CCx status (P = 0.0367). Analysing corresponding tissues six muscle and eight visceral adipose tissue (VAT) cachexia-associated miRNAs were identified. miR-27b-3p, miR-375 and miR-424-5p were the most consistently affected miRNAs in tissues of CCx patients correlating negatively with the severity of body weight loss (P = 0.0386, P = 0.0112 and P = 0.0075, respectively). We identified numerous putative target genes of the miRNAs in association with muscle atrophy and lipolysis pathways. Knock-down experiments in C2C12 myoblast cells revealed an association of miR-27b-3p and the in silico predicted atrophy-related target genes IL-15 and TRIM63. Both were up-regulated in miR-27b-3p knock-down cells (P < 0.05). Concordantly, in muscle tissue of CCx individuals, significant higher expression levels of IL-15 (P = 0.0237) and TRIM63 (P = 0.0442) were detected. miR-424-5p was identified to regulate the expression of lipase genes. Knock-down experiments in human visceral preadipocytes revealed an inverse association of miR-424-5p with its predicted target genes LIPE, PNPLA2, MGLL and LPL (P < 0.01). Conclusions The identified miRNAs, in particular miR-122-5p, miR-27b-3p, miR-375 and miR-424-5p, represent features of human CCx and may contribute to tissue wasting and skeletal muscle atrophy through the regulation of catabolic signals. Further studies are needed to explore the potential of the identified miRNAs as a screening tool for early detection of cancer cachexia.

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“…Overexpression of miR-375 in 3T3-L1 cells enhanced adipocyte differentiation by reducing ERK1/2 phosphorylation and increased the mRNA expression of key differentiation transcription factors (CEBPα and PPARγ) and aP2, which results in triglyceride accumulation. Seeliger et al [31] demonstrated that miR-375 knockdown during visceral preadipocyte differentiation upregulated the adipogenesis marker genes ADIPOQ and ADIPOR2. Gezginci-Oktayoglu et al ( 2020) reported that reducing miR-375 expression improved Erk1 expression in ARIP cells, and suppression of miR-375 suppressed the expression of the adipogenesis markers PPAR2, LPL, GLUT4, and leptin.…”

Section: Discussionmentioning

confidence: 99%

“…Species Target Regulation Function of Gene Mus musculus [30] CEBPα Up Transcription factor that directly promotes expression of the adipogenic genes PPARγ Up Cooperative induction of adipogenesis with CEBPα FABP4 Up Fatty acid uptake and transport for storage as triglycerides in lipid droplets Homo sapiens [31,32] ADIPOQ Down Adiponectin hormone, regulates blood glucose levels and promotes the degradation of fatty acids…”

Section: Table 2 Regulation Of Gene Expression By Mir-375 In Differen...mentioning

confidence: 99%

SNPs in microRNA Seed Region and Impact of miR-375 in Concurrent Regulation of Multiple Lipid Accumulation-related Genes

Lee,

Hong,

Lee

et al. 2024

Preprint

View full text Add to dashboard Cite

Bovine intramuscular fat (IMF), commonly referred to as marbling, is regulated by lipid metabolism, which includes adipogenesis, lipogenesis, glycerolipid synthesis, and lipolysis. In recent years, breeding researchers have identified single nucleotide polymorphisms (SNPs) as useful marker-assisted selection tools for improving marbling scores in national breeding programs. These included causal SNPs that induce phenotypic variation. MicroRNAs (miRNAs) are small highly conserved non-coding RNA molecules that bind to multiple non-coding regions. They are involved in post-transcriptional regulation. Multiple miRNAs may regulate a given target. Previously, three SNPs in the GPAM 3' UTR and four miRNAs were identified through in silico assays. This study aimed to verify the binding ability of the four miRNAs to the 3' UTR of the GPAM gene and identify their multifunctional role in adipocytes. We verified that the four miRNAs bound to the GPAM 3'UTR and identified that the miR-375 sequence is highly conserved. Furthermore, we found that miR-375 upregulated the GPAM gene and other lipid metabolism-related genes and promoted lipid droplet accumulation in 3T3-L1 cells. In conclusion, these results suggest that miR-375 is a multifunctional regulator of multiple lipid metabolism-related genes and may aid in obesity research as a biomarker.

show abstract

miR-375 is cold exposure sensitive and drives thermogenesis in visceral adipose tissue derived stem cells

Cited by 10 publications

References 73 publications

SNPs in microRNA seed region and impact of miR-375 in concurrent regulation of multiple lipid accumulation-related genes

SNPs in microRNA seed region and impact of miR-375 in concurrent regulation of multiple lipid accumulation-related genes

Specific miRNAs are associated with human cancer cachexia in an organ‐specific manner

SNPs in microRNA Seed Region and Impact of miR-375 in Concurrent Regulation of Multiple Lipid Accumulation-related Genes

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