ADIPOR1
Adiponectin receptor protein 1 (Progestin and adipoQ receptor family member 1) (Progestin and adipoQ receptor family member I) [PAQR1] [TESBP1A] [CGI-45]
Publications[править]
[i]DNA (cytosine-5)-methyltransferase 3a[/i] ([i]Dnmt3a[/i]) is an enzyme that catalyzes the transfer of methyl groups to specific CpG forms in DNA. In mammals, two variant transcripts of [i]Dnmt3a[/i] have been successfully identified. To the best of our knowledge, no [i]Dnmt3a[/i] transcripts in an avian have been successfully identified. This study was performed to detect different transcripts of [i]Dnmt3a[/i] in chickens and to examine whether a novel [i]Dnmt3a[/i] transcript named [i]Dnmt3a1[/i] may regulate adipogenesis. In addition to cloning, sequencing, transcript detection, and expression studies, a novel [i]Dnmt3a1[/i] transcript overexpression and knockdown were conducted to explore the potential role of [i]Dnmt3a1[/i] in preadipocyte proliferation and the early stage of adipocyte differentiation. In chicken abdominal fat tissue, we detected a novel [i]Dnmt3a1[/i] transcript that differs from [i]Dnmt3a[/i] by lacking 23 amino acids at the exon-1/exon-2 border. [i]Dnmt3a1[/i] mRNA was ubiquitously expressed in a variety of tissues or cells and highly expressed in chicken adipose tissue/cells. The expression of [i]Dnmt3a1[/i] was regulated under different physiological conditions including aging, fasting, and high-fat diet. In addition, overexpression of [i]Dnmt3a1[/i] significantly decreased preadipocyte proliferation and induced cell-cycle arrest while its inhibition increased cell proliferation and S-phase cells. Furthermore, the overexpression of [i]Dnmt3a1[/i] significantly upregulated the mRNA level of cell-cycle-related genes, such as [i]CDKN1A[/i], [i]CDKN1B[/i], [i]CCNB3[/i], [i]CCND2[/i], [i]CCNG2[/i], [i]CDKN2B[/i], and [i]CDK9[/i], or the protein level of CDKN1A, CDKN1B, and CCNG2. Conversely, the knockdown of [i]Dnmt3a1[/i] by siRNA had the opposite effects. Moreover, during early adipocyte differentiation, the overexpression of [i]Dnmt3a1[/i] significantly decreased the mRNA and the protein levels of PPAR-γ, C/EBP-α, ADIPOR1, and STAT3, and the mRNA levels of [i]FAS[/i], [i]LEPR[/i], [i]LPL[/i], [i]PRKAB2[/i], and [i]ATGL.[/i] In contrast, their expression was significantly increased after the knockdown of [i]Dnmt3a1[/i]. Taken together, we identified a novel transcript of [i]Dnmt3a[/i], and it played a potential role in adipogenesis.
Keywords
- Dnmt3a
- Dnmt3a1 transcript
- aging
- early differentiation
- expression
- high-fat diet
- preadipocytes proliferation
Age-related hearing impairment (ARHI) is a complex neurodegenerative disorder caused by a combination of environmental and genetic factors. We have reported previously that obesity increases the risk for ARHI, and that plasma levels of adiponectin are associated with ARHI. In the present study, we further explored the role of adiponectin in the pathophysiology of ARHI by investigating the genotypes of ADIPOQ and ADIPOR1, the genes of adiponectin and its type 1 receptor, respectively. A total of 1682 volunteers were enrolled, and their audiological phenotypes were determined according to the z scores converted from their original frequency-specific hearing thresholds. A total of 9 tag-single nucleotide polymorphisms (tagSNPs) in ADIPOQ and 4 tagSNPs in ADIPOR1 were genotyped, and the genotypes were correlated to the audiological phenotypes under the assumption of various inheritance models. Significant associations were identified between certain ADIPOQ tagSNPs and z scores under dominant, codominant, or additive models, whereas no association was identified between ADIPOR1 tagSNPs and z scores. The associations between ADIPOQ tagSNPs and z scores appear to exist only in subjects with specific ADIPOR1 genotypes, indicating an interaction between adiponectin and AdipoR1. Measurement of plasma adiponectin in 736 subjects revealed that ADIPOQ genotypes might exert their effects on hearing levels via modulation of plasma adiponectin levels. Subsequently, we confirmed the expression of AdipoR1 in the inner ear of mice, and demonstrated antiapoptotic effects of adiponectin in cochlear explant cultures. These results provide insights into the physiological function and potential clinical implications of adiponectin against ARHI.
MeSH Terms
- Adiponectin
- Adult
- Aged
- Aged, 80 and over
- Aging
- Animals
- Apoptosis
- Cells, Cultured
- Cochlea
- Ear, Inner
- Epistasis, Genetic
- Female
- Genetic Association Studies
- Genotype
- Hearing Loss
- Humans
- Male
- Mice
- Middle Aged
- Polymorphism, Single Nucleotide
- Receptors, Adiponectin
Keywords
- ADIPOR1
- Adiponectin
- Age-related hearing impairment