Long Noncoding RNAs: Novel Important Players in Adipocyte Lipid Metabolism and Derivative Diseases

Obesity, a global public health issue, is characterized by excessive adiposity and is strongly related to some chronic diseases including cardiovascular diseases and diabetes. Extra energy intake-induced adipogenesis involves various transcription factors and long noncoding RNAs (lncRNAs) that control lipogenic mRNA expression. Currently, lncRNAs draw much attention for their contribution to adipogenesis and adipose tissue function. Increasing evidence also manifests the pivotal role of lncRNAs in modulating white, brown, and beige adipose tissue development and affecting the progression of the diseases induced by adipose dysfunction. The aim of this review is to summarize the roles of lncRNAs in adipose tissue development and obesity-caused diseases to provide novel drug targets for the treatment of obesity and metabolic diseases.

Characteristics and expression profiles of circRNAs during abdominal adipose tissue development in Chinese Gushi chickens

Circular RNAs (circRNAs) play important roles in adipogenesis. However, studies on circRNA expression profiles associated with the development of abdominal adipose tissue are lacking in chickens. In this study, 12 cDNA libraries were constructed from the abdominal adipose tissue of Chinese domestic Gushi chickens at 6, 14, 22, and 30 weeks. A total of 1,766 circRNAs were identified by Illumina HiSeq 2500 sequencing. These circRNAs were primarily distributed on chr1 through chr10 and sex chromosomes, and 84.95% of the circRNAs were from gene exons. Bioinformatic analysis showed that each circRNA has 35 miRNA binding sites on average, and 62.71% have internal ribosome entry site (IRES) elements. Meanwhile, these circRNAs were primarily concentrated in TPM < 0.1 and TPM > 60, and their numbers accounted for 18.90% and 80.51%, respectively, exhibiting specific expression patterns in chicken abdominal adipose tissue. In addition, 275 differentially expressed (DE) circRNAs were identified by comparison analysis. Functional enrichment analysis showed that the parental genes of DE circRNAs were primarily involved in biological processes and pathways related to lipid metabolism, such as regulation of fat cell differentiation, fatty acid homeostasis, and triglyceride homeostasis, as well as fatty acid biosynthesis, fatty acid metabolism, and glycerolipid metabolism. Furthermore, ceRNA regulatory networks related to abdominal adipose development were constructed. The results of this study indicated that circRNAs can regulate lipid metabolism, adipocyte proliferation and differentiation, and cell junctions during abdominal adipose tissue development in chickens through complex ceRNA networks between circRNAs, miRNAs, genes, and pathways. The results of this study may help to expand the number of known circRNAs in abdominal adipose tissue and provide a valuable resource for further research on the function of circRNAs in chicken abdominal adipose tissue.

Human Milk Drives the Intimate Interplay Between Gut Immunity and Adipose Tissue for Healthy Growth

As the physiological food for the developing child, human milk is expected to be the diet that is best adapted for infant growth needs. There is also accumulating evidence that breastfeeding influences long-term metabolic outcomes. This review covers the potential mechanisms by which human milk could regulate healthy growth. We focus on how human milk may act on adipose tissue development and its metabolic homeostasis. We also explore how specific human milk components may influence the interplay between the gut microbiota, gut mucosa immunity and adipose tissue. A deeper understanding of these interactions may lead to new preventative and therapeutic strategies for both undernutrition and other metabolic diseases and deserves further exploration.

PPA1 Regulates Systemic Insulin Sensitivity by Maintaining Adipocyte Mitochondria Function as a Novel PPARγ Target Gene

<a>Downregulation of mitochondrial function in adipose tissue is considered as one important driver for the development of obesity-associated metabolic disorders. Inorganic Pyrophosphatase 1 (PPA1) is an enzyme catalyzes the hydrolysis of PPi to Pi, and is required for anabolism to take place in cells. Although alternation of PPA1 has been related to some diseases, the importance of PPA1 in metabolic syndromes has never been discussed before. In this study, we found that global PPA1 knockout mice (PPA1^+/-) showed impaired glucose tolerance and severe insulin resistance under HFD feeding. In addition, impaired adipose tissue development and ectopic lipid accumulation were also observed. Conversely, overexpression of PPA1 in adipose tissue by AAV injection can partly reverse the metabolic disorders in PPA1^+/- mice, suggesting that impaired adipose tissue function is responsible for the metabolic disorders observed in PPA1^+/-mice. Mechanistic studies revealed that PPA1 acted as a PPARγ target gene to maintain mitochondrial function in adipocytes. Furthermore, specific knockdown of PPA1 in fat body of <i>Drosophila</i> led to impaired mitochondria morphology, decreased lipid storage, and made <i>Drosophila</i> more sensitive to starvation. In conclusion, for the first time, our findings demonstrated the importance of PPA1 in maintaining adipose tissue function and whole body metabolic homeostasis.</a>

PPA1 Regulates Systemic Insulin Sensitivity by Maintaining Adipocyte Mitochondria Function as a Novel PPARγ Target Gene

<a>Downregulation of mitochondrial function in adipose tissue is considered as one important driver for the development of obesity-associated metabolic disorders. Inorganic Pyrophosphatase 1 (PPA1) is an enzyme catalyzes the hydrolysis of PPi to Pi, and is required for anabolism to take place in cells. Although alternation of PPA1 has been related to some diseases, the importance of PPA1 in metabolic syndromes has never been discussed before. In this study, we found that global PPA1 knockout mice (PPA1^+/-) showed impaired glucose tolerance and severe insulin resistance under HFD feeding. In addition, impaired adipose tissue development and ectopic lipid accumulation were also observed. Conversely, overexpression of PPA1 in adipose tissue by AAV injection can partly reverse the metabolic disorders in PPA1^+/- mice, suggesting that impaired adipose tissue function is responsible for the metabolic disorders observed in PPA1^+/-mice. Mechanistic studies revealed that PPA1 acted as a PPARγ target gene to maintain mitochondrial function in adipocytes. Furthermore, specific knockdown of PPA1 in fat body of <i>Drosophila</i> led to impaired mitochondria morphology, decreased lipid storage, and made <i>Drosophila</i> more sensitive to starvation. In conclusion, for the first time, our findings demonstrated the importance of PPA1 in maintaining adipose tissue function and whole body metabolic homeostasis.</a>

Transcriptome analysis of ciliary-dependent MCH signaling in differentiating 3T3-L1 pre-adipocytes

An understanding of adipocyte responsiveness to G-protein-coupled receptor-(GPCR) derived signals must take into consideration the role of membrane microenvironments; that individual sub-populations of proteins may vary significantly across different regions of the cell, and that cell differentiation alters those microenvironments. 3T3-L1 pre-adipocytes undergo a dramatic phenotypic transformation during differentiation into adipocytes, requiring the development of a transient primary cilium. We demonstrate that melanin-concentrating hormone (MCH) receptor 1, a GPCR that stimulates appetite, translocates to the transient primary cilium during early 3T3-L1 cell adipogenesis. Furthermore, we used RNA-Seq to investigate whether MCH signaling is influenced by its receptor localization and whether MCH can influence the transcriptome of early adipocyte development. We found that MCH signaling is sensitive to receptor localization to cilia, and this alters the adipogenic transcriptional program. Also, novel MCH signaling pathways in 3T3-L1 cells are identified, including those for circadian rhythm, the inflammatory response, and ciliary biogenesis. The presence of active MCH-signaling pathways in pre-adipocytes and the discovery that these pathways intersect with the early adipogenic program, among other newly-identified signaling pathways, suggests that the use of MCH receptor 1 antagonists for clinical interventions may have unintended consequences on adipose tissue development.

Lycopene supplementation of maternal and weanling high-fat diets influences adipose tissue development and metabolic outcomes of Sprague-Dawley offspring

Dietary patterns high in fat contribute to the onset of cardiometabolic disease through the accrual of adipose tissue (AT). Lycopene, a carotenoid shown to exert multiple health benefits, may disrupt these metabolic perturbations. The purpose of the present study was to evaluate AT development and obesity-associated metabolic outcomes in the neonate and weanling offspring of Sprague-Dawley mothers fed a high-fat diet (HFD = 50 % fat) with and without lycopene supplementation. Sprague-Dawley rats consumed either a normal fat diet (NFD; 25 % fat) or HFD throughout gestation. Upon delivery, half of HFD mothers were transitioned to an HFD supplemented with 1 % lycopene (HFDL). At postnatal day 14 (P14), P25, and P35, pups were euthanised, body weight was recorded, and visceral white AT (WAT) and brown AT (BAT) mass were determined. Serum redox status, adipokines, glucose and inflammatory biomarkers were evaluated, as well as BAT mRNA expression of uncoupling protein 1 (UCP1). The HFD was effective in inducing weight gain as evident by significantly greater BW and WAT in the HFD group compared to the NFD group across all time points. Compared to HFD, the HFDL group exhibited significantly greater BAT with concomitant reductions in WAT mass, serum lipid peroxides and serum glucose. No significant differences were observed in serum adipokines, inflammatory markers or UCP1 expression despite the aforementioned alterations in AT development. Results suggest that dietary lycopene supplementation may influence metabolic outcomes during the weaning and post-weaning periods. Additional research is warranted to elucidate molecular mechanisms by which lycopene influences AT biology.

Canine colostrum exosomes: characterization and influence on the canine mesenchymal stem cell secretory profile and fibroblast anti-oxidative capacity

Background Canine colostrum milk (CCM) is a specific secretion of the mammary gland that is fundamental for the survival of the newborn. CCM has many described components (immunoglobulins, proteins or fat), but its small vesicles, named exosomes, are largely unknown. Results A characterization of CCM exosomes was performed. Exosomes were abundant in CCM and appeared with the characteristic cup-shaped morphology and well-defined round vesicles. The size distribution of exosomes was between 37 and 140 nm, and western blot analysis showed positive expression of specific exosomal markers. Proteomic analysis revealed a total of 826 proteins in exosome cargo. We also found that exosomes modified the proliferation and secretory profiles in canine mesenchymal stem cells derived from bone marrow (cBM-MSCs) and adipose tissue (cAd-MSCs). Additionally, CCM exosomes demonstrated a potent antioxidant effect on canine fibroblasts in culture. Conclusions Our findings highlight, for the first time, the abundant presence of exosomes in CCM and their ability to interact with mesenchymal stem cells (MSCs). The addition of exosomes to two types of MSCs in culture resulted in specific secretory profiles with functions related to angiogenesis, migration and chemotaxis of immune cells. In particular, the cAd-MSCs secretory profile showed higher potential in adipose tissue development and neurogenesis, while cBM-MSC production was associated with immunity, cell mobilization and haematopoiesis. Finally, exosomes also presented antioxidant capacity on fibroblasts against reactive oxygen species activity within the cell, demonstrating their fundamental role in the development and maturation of dogs in the early stages of their life.