RÉSUMÉ
Adipose tissue is a key determinant of whole-body metabolism and energy homeostasis. Unravelling the transcriptional regulatory process during adipogenesis is therefore highly relevant from a biomedical perspective. In these studies, zinc finger protein B-cell lymphoma 6 (Bcl6) was demonstrated to have a role in early adipogenesis of mesenchymal stem cells. Bcl6 is enriched in preadipose versus non-preadipose fibroblasts and shows upregulated expression in the early stage of adipogenesis. Gain- and loss-of-function studies revealed that Bcl6 acts as a key regulator of adipose commitment and differentiation both in vitro and ex vivo RNAi-mediated knockdown of Bcl6 in C3H10T1/2 cells greatly inhibited adipogenic potential, whereas Bcl6 overexpression enhanced adipogenic differentiation. This transcription factor also directly or indirectly targets and controls the expression of some early and late adipogenic regulators (i.e. Zfp423, Zfp467, KLF15, C/EBPδ, C/EBPα and PPARγ). We further identified that Bcl6 transactivated the signal transducers and activators of transcription 1 (STAT1), which was determined as a required factor for adipogenesis. Moreover, overexpression of STAT1 rescued the impairment of adipogenic commitment and differentiation induced by Bcl6 knockdown in C3H10T1/2 cells, thereby confirming that STAT1 is a downstream direct target of Bcl6. This study identifies Bcl6 as a positive transcriptional regulator of early adipose commitment.
Sujet(s)
Adipogenèse , Protéines proto-oncogènes c-bcl-6/métabolisme , Facteur de transcription STAT-1/génétique , Cellules 3T3-L1 , Tissu adipeux/cytologie , Animaux , Différenciation cellulaire , Régulation de l'expression des gènes , Techniques de knock-down de gènes , Cellules souches mésenchymateuses , Souris , Cellules NIH 3T3 , Régions promotrices (génétique) , Protéines proto-oncogènes c-bcl-6/génétique , Activation de la transcriptionRÉSUMÉ
Juvenile hormone (JH) contributes to the regulation of larval molting and metamorphosis in insects. Herein, we comprehensively identified 55 genes involved in JH biosynthesis, metabolism and signaling in the silkworm (Bombyx mori) as well as 35 in Drosophila melanogaster, 35 in Anopheles gambiae, 36 in Apis mellifera, 47 in Tribolium castaneum, and 44 in Danaus plexippus. Comparative analysis showed that each gene involved in the early steps of the mevalonate (MVA) pathway, in the neuropeptide regulation of JH biosynthesis, or in JH signaling is a single copy in B. mori and other surveyed insects, indicating that these JH-related pathways or steps are likely conserved in all surveyed insects. However, each gene participating in the isoprenoid branch of JH biosynthesis and JH metabolism, together with the FPPS genes for catalyzing the final step of the MVA pathway of JH biosynthesis, exhibited an obvious duplication in Lepidoptera, including B. mori and D. plexippus. Microarray and real-time RT-PCR analysis revealed that different copies of several JH-related genes presented expression changes that correlated with the dynamics of JH titer during larval growth and metamorphosis. Taken together, the findings suggest that duplication-derived copy variation of JH-related genes might be evolutionarily associated with the variation of JH types between Lepidoptera and other insect orders. In conclusion, our results provide useful clues for further functional analysis of JH-related genes in B. mori and other insects.
RÉSUMÉ
Fumonisins are mycotoxins produced by Fusarium spp. and commonly contaminate maize and maize products worldwide. Fumonisins are rodent carcinogens and have been associated with human esophageal cancer. However, the lack of a valid exposure biomarker has hindered both the assessment of human exposure and the evaluation of disease risk. A sensitive liquid chromatography-mass spectrometry method to measure urinary fumonisin B1 (FB1) following extraction on Oasis MAX cartridges was established and applied to urine samples from women in a cohort recruited in Morelos County, Mexico. Urinary FB1 was compared with dietary information on tortilla consumption. FB1 recovery in spiked samples averaged 94% as judged by deuterium-labeled FB1 internal standard. Urinary FB1 was determined in 75 samples from women selected based on low, medium, or high consumption of maize-based tortillas. The geometric mean (95% confidence interval) of urinary FB1 was 35.0 (18.8-65.2), 63.1 (36.8-108.2), and 147.4 (87.6-248.0) pg/mL and the frequency of samples above the detection limit (set at 20 pg FB1/mL urine) was 45%, 80%, and 96% for the low, medium, and high groups, respectively. Women with high intake had a 3-fold higher average FB1 levels compared with the "low intake" group (F = 7.3; P = 0.0015). Urinary FB1 was correlated with maize intake (P(trend) = 0.001); the correlation remained significant after adjusting for age, education, and place of residence. This study suggests that measurement of urinary FB1 is sufficiently sensitive for fumonisin exposure assessment in human populations and could be a valuable tool in investigating the associated health effects of exposure.
Sujet(s)
Cancérogènes environnementaux/analyse , Fumonisines/urine , Mycotoxines/urine , Zea mays/microbiologie , Adolescent , Adulte , Analyse de variance , Chromatographie en phase liquide à haute performance , Femelle , Humains , Modèles linéaires , MexiqueRÉSUMÉ
The MYF5 gene is first inducibly expressed in muscle cell during embryonic muscle development and plays an important role in regulating the differentiation of skeletal muscle precursors. In this study we used PCR-RFLP to investigate two pig (Sus scrofa) populations (n = 302) for two MYF5 gene polymorphisms, a previously unreported novel Met-Leu shift single nucleotide polymorphism (SNP) MYF5/Hsp92II located on exon 1 and the previously identified intron 1 MYF5/HinfI SNP. Haplotype and association analysis showed that haplotypes of the two SNPs were significantly associated with drip loss rate (DLR, p < 0.05), water holding capacity (WHC, p < 0.05), biceps femoris meat color value (MCV2, p < 0.05), biceps femoris marbling score (MM2, p < 0.01), longissimus dorsi intramuscular fat percentage (IMF, p < 0.01) and longissimus dorsi Water moisture content (WM, p < 0.01) in the population 2. However, further studies are needed to confirm these preliminary results.