Abstract
Long non-coding RNAs (lncRNAs) have emerged as integral regulators of pathophysiological processes, but their specific roles and mechanisms in adipose tissue development remain largely unknown. Here, through microarray analysis, co-expression, and tissue specific analysis of adipocyte tissues after fasting for 72 h, we found that Lnc-FR332443 expression was dramatically decreased, as well as the expression of Runx1. The UCSC database and Ensembl database indicated that Lnc-FR332443 is the antisense lncRNA of Runx1. Lnc-FR332443 and Runx1 are highly enriched in adipose tissue and downregulated during adipogenic differentiation. Adipose tissue-specific knockdown of Lnc-FR332443 increased fat mass in vivo, and specific knockdown of Lnc-FR332443 in 3T3-L1 preadipocytes promoted adipogenic differentiation. In this process, Runx1 expression was decreased when Lnc-FR332443 was downregulated in adipocytes or 3T3-L1 preadipocytes, and vice versa, when Lnc-FR332443 was upregulated, the expression of Runx1 was increased. However, overexpression of Runx1 decreased the expression of the adipocyte cell marker genes PPARγ, C/EBPα and FABP4 significantly, while not affected the expression of Lnc-FR332443. Mechanistically, Lnc-FR332443 positively regulates Runx1 expression in mouse adipocytes and suppresses adipocyte differentiation by attenuating the phosphorylation of MAPK-p38 and MAPK-ERK1/2 expression. Thus, this study indicated that Lnc-FR332443 inhibits adipogenesis and which might be a drug target for the prevention and treatment of obesity.
Highlights
Obesity is related to a series of metabolic abnormalities and has become an international public health issue that affects quality of life, increases the risk of diseases and shortens life expectancy
After C57BL/6J male mice were fasted for 72 h (F72h), mesenteric white adipose tissue (mWAT) mass showed the greatest consumption compared to other regions of adipose tissue (Tang et al, 2017)
To further identify Long non-coding RNAs (lncRNAs) selectively involved in adipocyte differentiation, we analyzed differential lncRNAs and mRNAs profiles in mWAT by microarrays, and found 677 downregulated lncRNAs and 513 upregulated lncRNAs (Figure 1A) among the total 54,030 LncRNAs (Supplementary Material 1) in the F72h mice compared to the control mice
Summary
Obesity is related to a series of metabolic abnormalities and has become an international public health issue that affects quality of life, increases the risk of diseases and shortens life expectancy. The specific mechanism of the occurrence and development of obesity is still unclear, and there are few effective drug targets. Long non-coding RNAs (lncRNAs) are a class of ncRNAs transcribed from the genome that do not encode proteins and are longer than 200 nt (Mercer et al, 2009). LncRNAs are widely involved in the occurrence and development of tumors (Huarte, 2015; Schmitt and Chang, 2016). LncRNAs have received increasing attention as new drug targets for obesity. Some studies have proven that non-coding RNAs play an important role in the occurrence and development of obesity (Ponting et al, 2009). To date, the specific regulatory mechanism of lncRNAs in adipogenic differentiation is still unclear, and there are few lncRNAs that can be used as targets of antiobesity drugs
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