CircMEF2C(2, 3) modulates proliferation and adipogenesis of porcine intramuscular preadipocytes by miR-383/671-3p/MEF2C axis.

Circular RNA is a special category of non-coding RNA that has emerged as epigenetic regulator of adipose tissue development. However, the mechanism governing intramuscular adipogenesis of circRNA remains largely uncharted. In this study, circMEF2C(2, 3), looped by MEF2C exons 2 and 3, was identified from the pig MEF2C gene. Expression of circMEF2C(2, 3) is upregulated in early stage of intramuscular adipogenesis and muscular tissue of lean pigs (DLY pig). Subsequently, overexpression or knockdown of circMEF2C(2, 3) reflected that it participates in promoting proliferation and inhibiting adipogenic differentiation in porcine intramuscular preadipocytes and murine C3H10T1/2 cells. Mechanically, circMEF2C(2, 3) competitively combined with miR-383 and miR-671-3p to the 3'-UTR of MEF2C, which maintains MEF2C expression in regulating proliferation and adipogenesis. In summary, circMEF2C(2, 3) is a key regulator in the proliferation and adipogenic differentiation of intramuscular adipogenesis, suggesting its potential as a multi-target strategy for adipose development and associated diseases.

The long non-coding RNA lncMYOZ2 mediates an AHCY/MYOZ2 axis to promote adipogenic differentiation in porcine preadipocytes.

Long non-coding RNAs (lncRNAs) play a vital role in regulating adipogenesis. However, the associated regulatory mechanisms have yet to be described in detail in pig. In this study, we demonstrate a critical role for lncMYOZ2 in adipogenesis from porcine preadipocytes. Specifically, lncMYOZ2 was more abundant in the adipose tissue of Mashen (fat-type) pigs than for Large White (lean-type) pigs, and knockdown of this lncRNA significantly inhibited the differentiation of porcine preadipocytes into adipocytes. Mechanistically, we used RNA pull-down and RIP assays to establish that lncMYOZ2 interacts with adenosylhomocysteinase (AHCY). Moreover, lncMYOZ2 knockdown increased promoter methylation of the target gene MYOZ2 and lowered its expression. Finally, we describe a positive regulatory role for MYOZ2 in adipogenesis. Collectively, these findings establish lncMYOZ2 as an important epigenetic regulator of adipogenesis via the aforementioned AHCY/MYOZ2 pathway, and provide insights into the role of lncRNAs in porcine adipose development.

HMG20A Inhibit Adipogenesis by Transcriptional and Epigenetic Regulation of MEF2C Expression.

Obesity and its associated metabolic disease do serious harm to human health. The transcriptional cascade network with transcription factors as the core is the focus of current research on adipogenesis and its mechanism. Previous studies have found that HMG domain protein 20A (HMG20A) is highly expressed in the early stage of adipogenic differentiation of porcine intramuscular fat (IMF), which may be involved in regulating adipogenesis. In this study, HMG20A was found to play a key negative regulatory role in adipogenesis. Gain- and loss-of-function studies revealed that HMG20A inhibited the differentiation of SVF cells and C3H10T1/2 cells into mature adipocytes. RNA-seq was used to screen differentially expressed genes after HMG20A knockdown. qRT-PCR and ChIP-PCR confirmed that MEF2C was the real target of HMG20A, and HMG20A played a negative regulatory role through MEF2C. HMG20A binding protein LSD1 was found to alleviate the inhibitory effect of HMG20A on adipogenesis. Further studies showed that HMG20A could cooperate with LSD1 to increase the H3K4me2 of the MEF2C promoter and then increase the expression of MEF2C. Collectively, these findings highlight a role for HMG20A-dependent transcriptional and epigenetic regulation in adipogenesis.

Naringenin Prevents Oxidative Stress and Inflammation in LPS-Induced Liver Injury through the Regulation of LncRNA-mRNA in Male Mice.

Inflammation accompanies hepatic dysfunction resulting from tissue oxidative damage. Naringenin (Nar), a natural flavanone, has known antioxidant and anti-inflammatory activities, but its mechanism of action in the regulation of liver dysfunction requires further investigation. In this study, the role of naringenin in lipopolysaccharide (LPS)-induced hepatic oxidative stress and inflammation was explored, as well as its mechanism by transcriptome sequencing. The results indicated that compared with the LPS group, Nar treatment caused a significant increase in the mRNA levels of antioxidant factors glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM), yet the expression of related inflammatory factors (MCP1, TNFα, IL-1ß and IL-6) showed less of an increase. RNA sequencing identified 36 differentially expressed lncRNAs and 603 differentially expressed mRNAs. KEGG enrichment analysis indicated that oxidative stress and inflammation pathways are meticulously linked with naringenin treatment. The Co-lncRNA-mRNA network was also constructed. Tissue expression profiles showed that lncRNA played a higher role in the liver. Subsequently, expression levels of inflammatory factors indicated that lncRNAs and target mRNAs were significantly reduced after naringenin treatment in mouse liver AML12 cells and obese mouse. These results suggest that naringenin helps to prevent liver dysfunction through the regulation of lncRNA-mRNA axis to reduce oxidative stress and inflammatory factors.