Impacts of Alternative Splicing Events on the Differentiation  of Adipocytes

Lin, Ji-Ping

doi:10.3390/ijms160922169

Cited by 25 publications

(25 citation statements)

References 115 publications

(153 reference statements)

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“…Specific to adipogenesis, differential promoter usage and alternative splicing are required for the expression of the canonical adipogenic transcription factor Ppar␥ (26 -28, 43). Other regulatory factors are also formed from alternative splicing, including nCOR1 and Lipin1 (33,43,44). In the present study, we identified distinct roles of each splicing factor in generating Pparg mRNA splice variants.…”

Section: Determining Adipogenic Factors In the 14-3-3 Interactomementioning

confidence: 51%

“…We were also able to detect novel adipogenic roles of Hnrpf and Hnrpk, members of the heterogeneous nuclear ribonucleoproteins (Hnrps), which facilitate mRNA splicing (40,41). Alternative splicing of mRNA is critical for maintaining genetic diversity and cell identity, in addition to the expression of key factors required for differentiation (42,43). Specific to adipogenesis, differential promoter usage and alternative splicing are required for the expression of the canonical adipogenic transcription factor Ppar␥ (26 -28, 43).…”

Section: Determining Adipogenic Factors In the 14-3-3 Interactomementioning

confidence: 99%

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Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA-splicing factors during adipogenesis

Mugabo

Sadeghi

Fang

et al. 2018

Journal of Biological Chemistry

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Adipogenesis involves a complex signaling network requiring strict temporal and spatial organization of effector molecules. Molecular scaffolds, such as 14-3-3 proteins, facilitate such organization, and we have previously identified 14-3-3ζ as an essential scaffold in adipocyte differentiation. The interactome of 14-3-3ζ is large and diverse, and it is possible that novel adipogenic factors may be present within it, but this possibility has not yet been tested. Herein, we generated mouse embryonic fibroblasts from mice overexpressing a tandem affinity purification (TAP) epitope-tagged 14-3-3ζ molecule. After inducing adipogenesis, TAP-14-3-3ζ complexes were purified, followed by MS analysis to determine the 14-3-3ζ interactome. We observed more than 100 proteins that were unique to adipocyte differentiation, 56 of which were novel interacting partners. Among these, we were able to identify previously established regulators of adipogenesis ( Ptrf/Cavin1) within the 14-3-3ζ interactome, confirming the utility of this approach to detect adipogenic factors. We found that proteins related to RNA metabolism, processing, and splicing were enriched in the interactome. Analysis of transcriptomic data revealed that 14-3-3ζ depletion in 3T3-L1 cells affected alternative splicing of mRNA during adipocyte differentiation. siRNA-mediated depletion of RNA-splicing factors within the 14-3-3ζ interactome, that is, of Hnrpf, Hnrpk, Ddx6, and Sfpq, revealed that they have essential roles in adipogenesis and in the alternative splicing of and the adipogenesis-associated gene In summary, we have identified novel adipogenic factors within the 14-3-3ζ interactome. Further characterization of additional proteins within the 14-3-3ζ interactome may help identify novel targets to block obesity-associated expansion of adipose tissues.

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Section: Determining Adipogenic Factors In the 14-3-3 Interactomementioning

confidence: 51%

Section: Determining Adipogenic Factors In the 14-3-3 Interactomementioning

confidence: 99%

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA-splicing factors during adipogenesis

Mugabo

Sadeghi

Fang

et al. 2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Alternative splicing of mRNA is critical for maintaining genetic diversity and cell identity, in addition to the expression of key factors required for differentiation (49,50). Specific to adipogenesis, differential promoter usage and alternative splicing are required for the expression of the canonical adipogenic transcription factor Pparγ (51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA splicing factors during adipogenesis

Mugabo

Sadeghi

Fang

et al. 2017

Preprint

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Adipogenesis is facilitated by a complex signaling network requiring strict temporal and spatial organization of effector molecules. Molecular scaffolds, such as 14-3-3 proteins, coordinate such events, and we have previously identified 14-3-3ζ as an essential scaffold in adipocyte differentiation. The interactome of 14-3-3ζ is large and diverse, and it is possible that novel adipogenic factors may be present within it. Mouse embryonic fibroblasts from mice over-expressing a TAP-epitope-tagged 14-3-3ζ molecule were generated, and following the induction of adipogenesis, TAP-14-3-3ζ complexes were purified, followed by mass spectrometry analysis to determine the 14-3-3ζ interactome. Over 100 proteins were identified as being unique to adipocyte differentiation, of which 56 were novel interacting partners. Previously established regulators of adipogenesis (ie, Ptrf/Cavin1 and Phb2) were found within the 14-3-3ζ interactome, confirming the ability of this approach to identify regulators of adipocyte differentiation. An enrichment of proteins in the interactome related to RNA metabolism, processing, and splicing was identified, and analysis of transcriptomic data revealed that 14-3-3ζ depletion in 3T3-L1 cells affected the alternative splicing of mRNA during adipocyte differentiation. Of the RNA splicing factors within the 14-3-3ζ interactome, depletion of Hnrnpf, Hnrnpk, Ddx6, and Sfpq by siRNA revealed essential roles of these proteins in adipogenesis and their roles in the alternative splicing of Lpin1. In summary, novel adipogenic factors can be detected within the 14-3-3ζ interactome, and further characterization of additional proteins within the 14-3-3ζ interactome has the potential of identifying novel targets to block the expansion of adipose tissue mass that occurs in obesity.

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“…There are two main types of adipose tissue: WAT, which is involved in the accumulation of triglycerides and the increase of which may lead to obesity; and brown adipose tissue, which metabolizes fatty acids to maintain body temperature (Cannon and Nedergaard, 2004). It is important to note that the imbalance in energy homeostasis has led to a substantial increase in obesity around the world and that obesity is frequently associated with the development of other metabolic syndromes, such as diabetes and hypertension (Lin, 2015). In the current experimental model, there were two groups that received the high-glucose diet and green tea, one group that received the green tea extract in the light phase of the day (the LPHGD group), and a third that received the extract in the dark phase of the day (the DPHGD group).…”

Section: Lxraβ and Nucleolar Protein Fibrillarin Expression In The LImentioning

confidence: 99%

Short-term effects of green tea chronotherapy on the metabolic homeostasis of mice on different diets

et al. 2017

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ABSTRACT. Biological rhythms can be defined as changes in physiological or behavioral variables that repeat at certain time intervals. Rhythms that last approximately 24 h are referred to as circadian rhythms. Modern lifestyles have drastically affected human habits, as well as the population's eating habits. These changes have generated an epidemic of metabolic syndromes, such as obesity and diabetes. In an attempt to combat obesity, populations have attempted to use many different herbal remedies and plant-based drugs, the most common of which is Camellia sinensis, or green tea. Most of the studies on the effects of C. sinensis on maintaining body weight have reported the involvement of this substance in lipid oxidation. The objective of this study was to evaluate how the administration of C. sinensis at different times of day influenced changes in body weight, blood glucose levels, and food intake of mice kept under different diet conditions. The structural organization of abdominal adipose tissue was also evaluated, as were certain aspects of lipid metabolism and overall synthetic activity in the liver, adipose tissue, and ovaries. The results obtained suggest that the intake of green tea in the light phase of the day stimulates weight loss, regardless of the diet ingested. Neither glucose levels nor the structural organization of adipose tissue was found to be altered in any of the experimental groups. Neither diet nor the time at which the green tea was administered was found to have any effects on the amount of food the mice consumed. The time at which green tea was consumed and the type of diet both influenced LXRaβ nuclear receptor expression, as well as the expression of fibrillarin in the liver and ovaries, although this influence was tissue specific.

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Impacts of Alternative Splicing Events on the Differentiation of Adipocytes

Cited by 25 publications

References 115 publications

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA-splicing factors during adipogenesis

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA-splicing factors during adipogenesis

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA splicing factors during adipogenesis

Short-term effects of green tea chronotherapy on the metabolic homeostasis of mice on different diets

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