Investigation and Functional Characterization of Rare Genetic Variants in the Adipose Triglyceride Lipase in a Large Healthy Working Population

Lu, L., Wang, F., Chen, X., Yuan, H., Tian, Y., Li, J., Shen, J., Tao, Z. and Fu, Y. 2011. cDNA cloning, expression and regulation analysis of goose adipose triglyceride lipase ( ATGL ) gene. Can. J. Anim. Sci. 91: 363–369. Adipose triglyceride lipase (ATGL) has an important role in adiposome turnover in mammals. In avian species, the ATGL gene has been reported in chicken, duck, quail, turkey and parrot. We describe here the cloning and characterization of the ATGL in goose. Goose ATGL encodes a 482-amino-acid protein, which contains a “GXSXG” motif and 169-amino acid “patatin” domain. The deduced goose ATGL protein shows more than 85% identity to the reported avian species. Quantitative real-time RT-PCR analysis reveals that the goose ATGL mRNA is more highly expressed in subcutaneous fat. We also identify changes of goose ATGL mRNA expression pattern after over-feeding treatment, which may reveal that expression of ATGL in obesity is tissue-specific in goose. Moreover, we conclude that the mRNA level of ATGL can be regulated by oleic acid in goose adipocytes.

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Identification and characterization of adipose triglyceride lipase (ATGL) gene in birds

Molecular Biology Reports ◽

10.1007/s11033-009-9941-4 ◽

2009 ◽

Vol 37 (7) ◽

pp. 3487-3493 ◽

Cited By ~ 6

Author(s):

Qinghua Nie ◽

Yongsheng Hu ◽

Liang Xie ◽

Chengguang Zhang ◽

Xu Shen ◽

...

Keyword(s):

Adipose Triglyceride Lipase ◽

Triglyceride Lipase ◽

Identification And Characterization

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Genetic variants of human organic anion transporter 4 demonstrate altered transport of endogenous substrates

AJP Renal Physiology ◽

10.1152/ajprenal.00312.2010 ◽

2010 ◽

Vol 299 (4) ◽

pp. F767-F775 ◽

Cited By ~ 19

Author(s):

James E. Shima ◽

Takafumi Komori ◽

Travis R. Taylor ◽

Doug Stryke ◽

Michiko Kawamoto ◽

...

Keyword(s):

Genetic Variants ◽

Drug Disposition ◽

Organic Anion ◽

Functional Characterization ◽

Organic Anion Transporter ◽

Loss Of Function ◽

Anion Transporter ◽

Endogenous Substrates ◽

Slc Transporter

Apical reabsorption from the urine has been shown to be important for such processes as the maintenance of critical metabolites in the blood and the excretion of nephrotoxic compounds. The solute carrier (SLC) transporter OAT4 ( SLC22A11) is expressed on the apical membrane of renal proximal tubule cells and is known to mediate the transport of a variety of xenobiotic and endogenous organic anions. Functional characterization of genetic variants of apical transporters thought to mediate reabsorption, such as OAT4, may provide insight into the genetic factors influencing the complex pathways involved in drug elimination and metabolite reclamation occurring in the kidney. Naturally occurring genetic variants of OAT4 were identified in public databases and by resequencing DNA samples from 272 individuals comprising 4 distinct ethnic groups. Nine total nonsynonymous variants were identified and functionally assessed using uptake of three radiolabeled substrates. A nonsense variant, R48Stop, and three other variants (R121C, V155G, and V155M) were found at frequencies of at least 2% in an ethnic group specific fashion. The L29P, R48Stop, and H469R variants displayed a complete loss of function, and kinetic analysis identified a reduced Vmax in the common nonsynonymous variants. Plasma membrane levels of OAT4 protein were absent or reduced in the nonfunctional variants, providing a mechanistic reason for the observed loss of function. Characterization of the genetic variants of reabsorptive transporters such as OAT4 is an important step in understanding variability in tubular reabsorption with important implications in innate homeostatic processes and drug disposition.

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