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      Haplotypes in the promoter region of the CIDEC gene associated with growth traits in Nanyang cattle

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          Abstract

          Cell death-inducing DFFA-like effector c (CIDEC, also known as Fsp27) has emerged as an important regulator of metabolism associated with lipodystrophy, diabetes, and hepatic steatosis. It is required for unilocular lipid droplet formation and optimal energy storage. The mechanism between this gene and livestock growth traits, however, has yet to be reported. In this study, we found ten novel single nucleotide polymorphisms (SNPs) in the 5’ transcriptional region of CIDEC in Nanyang (NY) cattle, which are located in the recognition sequences (potential cis-acting elements) of 22 transcription factors, and the nine haplotypes represent nine different combinations of polymorphic potential cis-acting elements. The results indicated that individuals with the H8-H8 diplotype had heavier body weights and faster growth rates ( P < 0.01) at 18th months than those with H1-H8. We evaluated the transcriptional activities of different haplotypes in vitro, the results were consistent with the association analysis. The H8 haplotype had 1.88-fold ( P < 0.001) higher transcriptional activity than the H1 haplotype. We speculate that the haplotypes of the potential cis-acting elements may affect the transcriptional activity of CIDEC, thus affecting the growth traits of cattle. This information may be used in molecular marker-assisted selection of cattle breeding in the future.

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          Most cited references19

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          DNA Pooling: a tool for large-scale association studies.

          DNA pooling is a practical way to reduce the cost of large-scale association studies to identify susceptibility loci for common diseases. Pooling allows allele frequencies in groups of individuals to be measured using far fewer PCR reactions and genotyping assays than are used when genotyping individuals. Here, we discuss recent developments in quantitative genotyping assays and in the design and analysis of pooling studies. Sophisticated pooling designs are being developed that can take account of hidden population stratification, confounders and inter-loci interactions, and that allow the analysis of haplotypes.
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            Hepatic steatosis in leptin-deficient mice is promoted by the PPARgamma target gene Fsp27.

            Peroxisome proliferator-activated receptor gamma (PPARgamma) is induced in leptin-deficient (ob/ob) mouse liver and is critical for the development of hepatic steatosis. The present study shows that fat-specific protein 27 (Fsp27) in ob/ob liver is a direct target gene of PPARgamma and can elevate hepatic triglyceride levels. FSP27 belongs to the CIDE family, composed of CIDE A, CIDE B, and FSP27/CIDE C, all of which contain a conserved CIDE-N domain. FSP27 was recently reported to be a lipid droplet-binding protein and to promote lipid accumulation in adipocytes. The Fsp27 gene was expressed at high levels in ob/ob liver and at markedly lower levels in ob/ob livers lacking PPARgamma. Forced expression of FSP27 by adenovirus in hepatocytes in vitro or in vivo led to increased triglyceride levels. Knockdown by adenovirus expressing FSP27 shRNA resulted in lower accumulation of hepatic triglycerides compared to control adenovirus-infected liver. Taken together, these results indicate that FSP27 is a direct mediator of PPARgamma-dependent hepatic steatosis.
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              Cidea is associated with lipid droplets and insulin sensitivity in humans.

              Storage of energy as triglyceride in large adipose-specific lipid droplets is a fundamental need in all mammals. Efficient sequestration of fat in adipocytes also prevents fatty acid overload in skeletal muscle and liver, which can impair insulin signaling. Here we report that the Cide domain-containing protein Cidea, previously thought to be a mitochondrial protein, colocalizes around lipid droplets with perilipin, a regulator of lipolysis. Cidea-GFP greatly enhances lipid droplet size when ectopically expressed in preadipocytes or COS cells. These results explain previous findings showing that depletion of Cidea with RNAi markedly elevates lipolysis in human adipocytes. Like perilipin, Cidea and the related lipid droplet protein Cidec/FSP27 are controlled by peroxisome proliferator-activated receptor gamma (PPARgamma). Treatment of lean or obese mice with the PPARgamma agonist rosiglitazone markedly up-regulates Cidea expression in white adipose tissue (WAT), increasing lipid deposition. Strikingly, in both omental and s.c. WAT from BMI-matched obese humans, expression of Cidea, Cidec/FSP27, and perilipin correlates positively with insulin sensitivity (HOMA-IR index). Thus, Cidea and other lipid droplet proteins define a novel, highly regulated pathway of triglyceride deposition in human WAT. The data support a model whereby failure of this pathway results in ectopic lipid accumulation, insulin resistance, and its associated comorbidities in humans.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                20 July 2015
                2015
                : 5
                : 12075
                Affiliations
                [1 ]College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture , Yangling Shaanxi 712100, People’s Republic of China
                [2 ]Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences , Zhengzhou Henan, 450002, People’s Republic of China
                [3 ]United States Department of Agriculture-Agricultural Research Service, Bovine Functional Genomics Laboratory , Beltsville, Maryland 20705, United States of America
                Author notes
                Article
                srep12075
                10.1038/srep12075
                4648405
                26189824
                3696ae42-085b-49d5-aae0-dca5569df455
                Copyright © 2015, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 18 March 2015
                : 16 June 2015
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