Molecular mechanisms of FOXO1 in adipocyte differentiation

Chen, Junye; Lü, Yi; Tian, Mengyuan; Huang, Qiren

doi:10.1530/jme-18-0178

Cited by 70 publications

(58 citation statements)

References 160 publications

(212 reference statements)

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“…Furthermore, INSIG molecules can also bind to HMGCR, inhibiting its use of cytosolic acetyl-CoA for cholesterol biosynthesis [117]. FOXO1 is regularly expressed in insulin responsive cells such as the adipocytes, is involved in their differentiation and can inhibit lipid synthesis by suppressing the transcriptional activity of PPARG [118]. This protein is also a suggested transcription factor with positive effect in myogenic growth, though studies are not consistent [119].…”

Section: Functional Analysismentioning

confidence: 99%

Comparative Transcriptomic Analysis of Subcutaneous Adipose Tissue from Local Pig Breeds

Albuquerque

Óvilo

Núñez

et al. 2020

Genes

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When compared to modern lean-type breeds, Portuguese local Alentejano (AL) and Bísaro (BI) pig breeds present a high potential for subcutaneous and intramuscular fat (IMF) deposition which contributes for better meat quality. The aim of this work was to explore the genome function to better understand the underlying physiological mechanisms associated with body fat accretion. Dorsal subcutaneous fat samples were collected at slaughter from adult animals (n = 4 for each breed) with~150 kg body weight. Total RNA was obtained and sequenced for transcriptome analysis using DESeq2. A total of 458 differentially expressed (DE) genes (q-value < 0.05) were identified, with 263 overexpressed in AL and 195 in BI. Key genes involved in de novo fatty acid biosynthesis, elongation and desaturation were upregulated in AL such as ACLY, FASN, ME1, ELOVL6 and SCD. A functional enrichment analysis of the DE genes was performed using Ingenuity Pathway Analysis. Cholesterol synthesis is suggested to be higher in AL via SREBF2, SCAP and PPARG, while lipolytic activity may be more active in BI through GH and AMPK signalling. Increased signalling of CD40 together with the predicted activation of INSIG1 and INSIG2 in BI suggests that this breed is more sensitive to insulin whereas the AL is less sensitive like the Iberian breed.Genes 2020, 11, 422 2 of 20 inherent genetic value for biodiversity, local breeds are used to produce high quality dry-cured meat products, representing an important role in local economies, culture and landscape as the basics of sustainable local pork chains [2,4].Alentejano (AL) and Bísaro (BI) are the two main Portuguese pig breeds. AL evolved from the primitive Sus scrofa mediterraneus, belongs to the Mediterranean group of breeds [5] and is genetically similar to the Iberian (IB) pig [6]. This breed is commonly raised in the south of Portugal and generally characterized by its light bone structure, black color, short and slim extremities and energetic nature [7]. A medium-sized pig, the AL grows at a low rate (except under the finishing phase "montanheira") and presents a low prolificacy [8]. On the other hand, its high and early adipogenic activity provides a meat and fat composition that is attractive for both fresh meat market and for processing high-grade sausage and dry cured products [9,10]. Traditionally, the AL pig is raised under extensive conditions in an integrated pastoral system ("montado") and during the fattening season is fed with acorns from the existing Quercus forests from October to February [5,7]. BI breed belongs to the Celtic group [5], sharing ancestors with highly productive breeds such as Large-White and Landrace. Production of BI is distributed throughout the north of Portugal, from the Tagus River to the northern border with Spain. It is characterized by its docile temperament, presenting a large body with large legs, head and shoulders. BI pig presents a higher prolificacy and productivity than AL, though lower than other genotypes with similar origins but raised under intensive ...

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Section: Functional Analysismentioning

confidence: 99%

Comparative Transcriptomic Analysis of Subcutaneous Adipose Tissue from Local Pig Breeds

Albuquerque

Óvilo

Núñez

et al. 2020

Genes

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“…Recently, forkhead box-O1 (FOXO1), one of the FOXO subtypes, has attracted attention as an antiobesity target molecule due to its diverse effects in cell cycle control and adipocyte differentiation [ 7 ]. Based on previous studies, FOXO1 was shown to be a tumor suppressor that regulates cell cycles in a variety of human cancers [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Once phosphorylated FOXO1 is separated from the promoter region of PPARγ, it is then followed by exclusion from the nucleus which results in PPARγ transcription. The inhibition of FOXO1 phosphorylation and augmentation of nuclear FOXO1 levels therefore suggests itself as a strategy for the suppression of adipogenesis [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Lignan from Alnus japonica Inhibits Adipocyte Differentiation via Cell Cycle and FOXO1 Regulation

2020

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In the present study, we isolated a lignan ((−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol, DFS) from Alnus japonica and evaluated its antiobesity potential in vitro. We also determined its mechanism of action in a mouse pre-adipocyte 3T3-L1 cell line. DFS dose- and day-dependently inhibited adipogenesis by downregulation of adipogenic factors and lipid metabolism-regulating factors during adipocyte differentiation. In particular, DFS suppressed cell cycle-regulating factors and induced G0/G1 cell cycle arrest, implying that it had an inhibitory effect on mitotic clonal expansion which occurred at an early stage of adipogenesis. DFS also suppressed adipogenesis through decreasing Akt phosphorylation and increasing the level of Forkhead box protein-O1 (FOXO1). These results suggest that DFS may be a pharmacological candidate for the development of antiobesity, therapeutic, and nutraceutical products.

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“…FOXO1 was found to be one of the most important substrate of AKT. It has been reported that the activated AKT induces phosphorylation of FOXO1 at 3 different serine/threonine residues and thus decrease the nuclear translocation of FOXO1 [ 16 ]. AKT/FOXO1 signaling pathway regulates many biological processs by modulating numerous target genes which are involved in apoptosis, autophagy and cell cycle arrest [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

FUT4siRNA augments the chemosensitivity of non-small cell lung cancer to cisplatin through activation of FOXO1-induced apoptosis

Gao

Liang

et al. 2020

BMC Cancer

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Background Increased fucosylation is associated with the chemoresistance phenotype. Meanwhile, fucosyltransferase IV (FUT4) amounts are frequently elevated in lung cancer and may be related to increased chemoresistance. Methods In the present work, FUT4’s role in cisplatin-induced apoptosis was assessed in A549 and H1975 cells, respectively. To clarify whether the FUT4 gene attenuates chemosensitivity in tumor cells, we constructed FUT4siRNA and evaluated its effects on cisplatin-induced apoptosis and cell growth inhibition. Cell viability, apoptosis, migration and invasion assay were conducted to investigate cisplatin sensitivity. The activation of EGFR/AKT/FOXO1 signaling were measured by western blot. The translocation of FOXO1 was assessed by IFC using Laser Scanning Confocal Microscope. Results We found that FUT4 knockdown dose-dependently increased cisplatin-associated cytotoxicity. Furthermore, FUT4 silencing induced apoptosis and inhibited proliferation in A549 and H1975 cells by suppressing Akt and FOXO1 phosphorylation induced by cisplatin administration, which resulted in nuclear translocation of FOXO1. Conclusion These results suggested FUT4 might control chemoresistance to cisplatin in lung cancer by suppressing FOXO1-induced apoptosis.

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Molecular mechanisms of FOXO1 in adipocyte differentiation

Cited by 70 publications

References 160 publications

Comparative Transcriptomic Analysis of Subcutaneous Adipose Tissue from Local Pig Breeds

Comparative Transcriptomic Analysis of Subcutaneous Adipose Tissue from Local Pig Breeds

Lignan from Alnus japonica Inhibits Adipocyte Differentiation via Cell Cycle and FOXO1 Regulation

FUT4siRNA augments the chemosensitivity of non-small cell lung cancer to cisplatin through activation of FOXO1-induced apoptosis

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