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Brown adipose tissue (BAT) plays a critical role in maintaining the body temperature in newborn lamb due to its unique non-shivering thermogenesis. Previous studies have found that BAT thermogenesis is regulated by several long non-coding RNAs (lncRNAs). Here, we identified a novel lncRNA, MSTRG.310246.1, which was enriched in BAT. MSTRG.310246.1 was localized in both the nuclear and cytoplasmic compartments. In addition, MSTRG.310246.1 expression was upregulated during brown adipocyte differentiation. Overexpression of MSTRG.310246.1 increased the differentiation and thermogenesis of goat brown adipocytes. On the contrary, the knockdown of MSTRG.310246.1 inhibited the differentiation and thermogenesis of goat brown adipocytes. However, MSTRG.310246.1 had no effect on goat white adipocyte differentiation and thermogenesis. Our results show that MSTRG.310246.1 is a BAT-enriched LncRNA that improves the differentiation and thermogenesis of goat brown adipocytes. [ABSTRACT FROM AUTHOR]

Simple Summary: In our study, we launched RNA-seq in order to investigate the potential functions of circRNA during brown adipose tissue (BAT) to white adipose tissue (WAT) transformation. As a result, 6610 circRNAs and 61 differentially expressed circRNAs (DEcircRNAs) were identified. Moreover, 65 miRNAs were detected that could potentially interact with DEcircRNAs. The present study provides a detailed circRNA expression landscape and evidence for circRNA functions in the transformation from BAT to WAT. Adipose tissues are mainly divided into brown adipose tissue (BAT) and white adipose tissue (WAT). WAT mainly functions to buffer excess calories, whereas BAT plays a role in the non-shivering thermogenesis to maintain body temperature and energy balance. Moreover, circRNAs play important roles in various biological processes. However, knowledge of the expression profile and function of circRNAs from BAT to WAT remains largely unknown. In this study, a total of 6610 unique circRNAs were identified in the perirenal adipose tissues of 1-day, 30-days, and 1-year goats. Functional annotation revealed that host genes of circRNAs were involved in some BAT-related pathways, such as the thyroid hormone signaling pathway, MAPK signaling pathway, and VEGF signaling pathway. Furthermore, a total of 61 DEcircRNAs were detected across three stages. Additionally, five selected circRNAs were validated by RNase R assay, qPCR, and Sanger sequencing. Finally, the circRNA–miRNA network was constructed between the DEcircRNAs and their miRNA binding sites. [ABSTRACT FROM AUTHOR]

Simple Summary: Brown adipose tissue (BAT) plays important roles in unique non-shivering thermogenesis. It is necessary to select reference genes during the transition process from brown (BAT) to white adipose tissue (WAT) for Quantitative PCR (qPCR) analysis. In this study, CTNNB, PFDN5 and EIF3M, selected from RNA sequencing data, were the most suitable reference genes. The present study provides a detailed analysis of the expression stability of reference genes for the study of gene expression profiling during the transition process from BAT to WAT. Brown adipose tissues have unique non-shivering thermogenesis functions, can be found in newborn ruminate animals, and then are gradually replaced by white adipose tissues in adulthood. For the purpose of exploring the intrinsic mechanism underlying the conversion process from brown (BAT) to white adipose tissue (WAT), it is necessary to utilize Quantitative PCR (qPCR) to study gene expression profiling. In this study, we identified reference genes that were consistently expressed during the transformation from goat BAT to WAT using RNA-seq data. Then, twelve genes were evaluated as candidate reference genes for qPCR in goat perirenal adipose tissue using three tools (geNorm, Normfinder, and BestKeeper). In addition, the selected reference genes were used to normalize the gene expression of PGC-1α and GPAT4. It was found that traditional reference genes, such as GAPDH, RPLP0, HPRT1, and PPIA were not suitable for target gene normalization. In contrast, CTNNB, PFDN5, and EIF3M, selected from RNA sequencing data, showed the least variation and were recommended as the best reference genes during the transformation from BAT to WAT. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) play an important role in the thermogenesis and energy storage of brown adipose tissue (BAT). However, knowledge of the cellular transition from BAT to white adipose tissue (WAT) and the potential role of lncRNAs in goat adipose tissue remains largely unknown. In this study, we analyzed the transformation from BAT to WAT using histological and uncoupling protein 1 (UCP1) gene analyses. Brown adipose tissue mainly existed within the goat perirenal fat at 1 day and there was obviously a transition from BAT to WAT from 1 day to 1 year. The RNA libraries constructed from the perirenal adipose tissues of 1 day, 30 days, and 1 year goats were sequenced. A total number of 21,232 lncRNAs from perirenal fat were identified, including 5393 intronic-lncRNAs and 3546 antisense-lncRNAs. Furthermore, a total of 548 differentially expressed lncRNAs were detected across three stages (fold change ≥ 2.0, false discovery rate (FDR) < 0.05), and six lncRNAs were validated by qPCR. Furthermore, trans analysis found lncRNAs that were transcribed close to 890 protein-coding genes. Additionally, a coexpression network suggested that 4519 lncRNAs and 5212 mRNAs were potentially in trans-regulatory relationships (r > 0.95 or r < −0.95). In addition, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that the targeted genes were involved in the biosynthesis of unsaturated fatty acids, fatty acid elongation and metabolism, the citrate cycle, oxidative phosphorylation, the mitochondrial respiratory chain complex, and AMP-activated protein kinase (AMPK) signaling pathways. The present study provides a comprehensive catalog of lncRNAs involved in the transformation from BAT to WAT and provides insight into understanding the role of lncRNAs in goat brown adipogenesis. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) plays an important role on no shivering thermogenesis during cold exposure to maintain animal body temperature and energy homeostasis. However, knowledge of the cellular transition from white adipose tissue (WAT) to BAT is still limited. In this study, we provided a comprehensive metabolomics and transcriptional signatures of goat BAT and WAT. A total of 157 metabolites were significantly changed, including 81 upregulated and 76 downregulated metabolites. In addition, we identified the citric acid cycle, fatty acid elongation, and degradation pathways as coordinately activated in BAT. Interestingly, five unsaturated fatty acids (Eicosadienoic Acid, C20:2; γ‐Linolenic acid, C20:3; Arachidonic Acid, C20:4; Adrenic acid, C22:4; Docosahexaenoic acid, C22:6), Succinate, L‐carnitine, and L‐palmitoyl‐carnitine were found to be abundant in BAT. Furthermore, L‐carnitine, an intermediate of fatty acid degradation, is required for goat brown adipocyte differentiation and thermogenesis through activating AMPK pathway. However, L‐carnitine decreased lipid accumulation through inducing lipolysis and thermogenesis in white adipocytes. These results revealed that there are the significant alterations in transcriptomic and metabolomic profiles between goat WAT and BAT, which may contribute to better understanding the roles of metabolites in BAT thermogenesis process. [ABSTRACT FROM AUTHOR]

Brown and beige adipose thermogenesis are important for newborn mammals to maintain their body temperature. In addition, these thermogenic fats are regulated by multiple molecular interactions. How the long non-coding RNAs (lncRNAs) regulate adipose thermogenesis in newborn mammals upon cold exposure remains unexplored. Here, we identified lncRNAs induced by cold exposure in brown adipose tissue (BAT) of newborn goats and found that lncDGAT2 was enriched in BAT after cold exposure. Functional studies revealed that lncDGAT2 promoted brown and white adipocyte differentiation as well as thermogenic gene expression. Additionally, PRDM4 directly bound the lncDGAT2 promoter to activate the transcription of lncDGAT2 and the PRDM4-lncDGAT2 axis was essential for the brown adipocyte thermogenic gene program. These findings provide evidence for lncRNA and transcription factor regulatory functions in controlling adipose thermogenesis and energy metabolism of newborn goats. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) is involved in various biological processes. However, the regulatory roles of circRNA on brown adipose tissue (BAT) thermogenesis still remain to be elucidated. In this study, we characterized circZEB1, which was enriched in BAT and derived from exon 2 and exon 3 of goat ZEB1 gene. Sanger sequencing and RNase R assay demonstrated that circZEB1 was a head-to-tail structure with a length of 298 bp. Besides, the expression levels of circZEB1 were upregulated during brown adipocytes differentiation and circZEB1 was mainly located in cytoplasm. Furthermore, circZEB1 promoted brown adipocytes differentiation and thermogenesis. Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay indicated that circZEB1 could bind to miR-326–3p in brown adipocytes. In addition, miR-326–3p reduced the lipid accumulation of brown adipocytes, whereas overexpression of circZEB1 reversed the inhibition effects of miR-326–3p on lipid deposition. The results demonstrated that circZEB1 regulated brown adipocytes differentiation and thermogenesis through circZEB1/miR-326–3p pathway. • We characterized circZEB1, which was enriched in BAT and derived from exon 2 and exon 3 of goat ZEB1 gene. • CircZEB1 promoted brown adipocytes differentiation and thermogenesis. • CircZEB1 regulated brown adipocytes differentiation and thermogenesis through circZEB1/miR-326–3p pathway. [ABSTRACT FROM AUTHOR]