Abstract
BackgroundLong non-coding RNAs (lncRNAs) regulate adipose tissue metabolism, however, their function on testosterone deficiency related obesity in humans is less understood. For this research, intact and castrated male pigs are the best model animal because of their similar proportional organ sizes, cardiovascular systems and metabolic features.ResultsWe identified lncRNAs in subcutaneous adipose tissue by deep RNA-sequencing using the intact and castrated Huainan male pigs. The results showed that castration reduced serum testosterone but increased body fatness-related traits (serum triglyceride levels, backfat thickness, intramuscular fat content, and adipocyte size). Meanwhile, 343 lncRNAs from subcutaneous adipose tissue were identified, including 223 intergenic lncRNAs (lincRNAs), 68 anti-sense lncRNAs, and 52 intronic lncRNAs. It was predicted that there were 416 recognition sites for C/EBPα in the 303 lncRNA promoter region, and 13 adipogenesis-promoting miRNAs and five adipogenesis-depressing miRNAs target these lncRNAs. Eighteen lncRNAs, including nine up- and nine down-regulated had more than 2-fold differential expression between the castrated and intact male pigs (q-value < 0.05). Functional analysis indicated that these 18 lncRNAs and their target genes were involved in fatty acid, insulin, and the adipocytokine signaling pathway. We further analyzed the features of a conserved mouse lncRNA gene ENSMUST00000189966 and found it mainly expressed in the cell nucleus and target the Nuclear Receptor Subfamily 2 Group F Member 2 (NR2F2) gene. In 3 T3-L1 cells, differentiation down-regulated their expression, but dihydrotestosterone (DHT) significantly up-regulated their expression in a concentration-dependent manner (P < 0.05).ConclusionsThese results suggested that lncRNAs and their target genes might participated in the castration-induced fat deposition and provide a new therapeutic target for combatting testosterone deficiency-related obesity.
Highlights
Long non-coding RNAs regulate adipose tissue metabolism, their function on testosterone deficiency related obesity in humans is less understood
Castration resulted in a significant increase in intramuscular fat content in male pigs’ longissimus dorsi muscle (LDM, P < 0.01) and psoas major muscle (PMM, P < 0.05, Table 1)
We found that 73.5% of the total Long non-coding RNAs (lncRNAs) had target genes, containing 3.4 isoforms per lncRNA locus on average, respectively
Summary
Long non-coding RNAs (lncRNAs) regulate adipose tissue metabolism, their function on testosterone deficiency related obesity in humans is less understood. Intact and castrated male pigs are the best model animal because of their similar proportional organ sizes, cardiovascular systems and metabolic features. The castrated male pigs, with the similar organ size, metabolic features, cardiovascular systems, are the best animal model for researching human testosterone deficiency-related diseases [3,4,5]. PU. ( known as SPI1, spleen focus forming virus (SFFV) proviral integration oncogene) inhibited adipogenesis by the downregulation of adipogenic master gene PPARγ [11], and its antisense long non-coding RNAs promotes adipogenesis by preventing its mRNA translation [12]. LncRNA ADNCR (adipocyte differentiation-associated long noncoding RNA) suppressed adipocyte differentiation by function as a ceRNA for miR-204, whose target geneSIRT1 was known to repress PPARγ activity and inhibit adipocyte differentiation [13]
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