Cross Species Association Examination of UCN3 and CRHR2 as Potential Pharmacological Targets for Antiobesity Drugs

Jiang, Zhihua; Michal, Jennifer J.; Williams, Galen; Daniels, Tyler F.; Kunej, Tanja

doi:10.1371/journal.pone.0000080

Cited by 18 publications

(14 citation statements)

References 23 publications

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“…Concerning CRHR2, although Jiang et al (2006) did not find Kraner et al (2002) and Thompson et al (2007) CRHR2 Corticotropin releasing hormone et al (2006) any association between several polymorphisms in this gene and intramyocellular lipid accumulation or subcutaneous fat depth in cattle, the data presented here show a significant link between this gene and the total amount of FA in muscle. Concerning CRHR2, although Jiang et al (2006) did not find Kraner et al (2002) and Thompson et al (2007) CRHR2 Corticotropin releasing hormone et al (2006) any association between several polymorphisms in this gene and intramyocellular lipid accumulation or subcutaneous fat depth in cattle, the data presented here show a significant link between this gene and the total amount of FA in muscle.…”

Section: Genes Affecting Total Fatty Acid Content In Musclecontrasting

confidence: 49%

Genes involved in muscle lipid composition in 15 European Bos taurus breeds

et al. 2013

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Consumers demand healthy and palatable meat, both factors being affected by fat composition. However, red meat has relatively high concentration of saturated fatty acids and low concentration of the beneficial polyunsaturated fatty acids. To select animals prone to produce particular fat types, it is necessary to identify the genes influencing muscle lipid composition. This paper describes an association study in which a large panel of candidate genes involved in adipogenesis, lipid metabolism and energy homoeostasis was tested for effects on fat composition in 15 European cattle breeds. Sixteen genes were found to have significant effects on different lipid traits, and among these, CFL1 and MYOZ1 were found to have large effects on the ratio of 18:2/18:3, CRI1 on the amount of neutral adrenic acid (22:4 n-6), MMP1 on docosahexaenoic acid (22:6 n-3) and conjugated linoleic acid, PLTP on the ratio of n-6:n-3 and IGF2R on flavour. Several genes - ALDH2, CHRNE, CRHR2, DGAT1, IGFBP3, NEB, SOCS2, SUSP1, TCF12 and FOXO1 - also were found to be associated with both lipid and organoleptic traits although with smaller effect. The results presented here help in understanding the genetic and biochemical background underlying variations in fatty acid composition and flavour in beef.

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Section: Genes Affecting Total Fatty Acid Content In Musclecontrasting

confidence: 49%

Genes involved in muscle lipid composition in 15 European Bos taurus breeds

et al. 2013

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“…Both cDNA and genomic DNA sequences of the bovine UTS2 and UTS2R were retrieved from the GenBank databases using a comparative approach, as previously described 17. Alignment between cDNA and genomic DNA sequences was used to determine genomic organization for each of these two genes.…”

Section: Methodsmentioning

confidence: 99%

Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus

Jiang¹,

Michal²,

Tobey³

et al. 2008

Int. J. Biol. Sci.

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Several reports have shown that urotensin 2 (UTS2) and its receptor (UTS2R) are involved in glucose metabolism and insulin resistance, which lead to development of type 2 diabetes mellitus (T2DM) in humans. In the present study, we annotated both bovine UTS2 and UTS2R genes and identified 5 single nucleotide polymorphisms (SNPs) for the former gene and 14 mutations for the latter gene. Four mutations were genotyped on a Wagyu x Limousin reference population, including 6 F 1 bulls, 113 F 1 dams and ~250 F 2 progeny. Among 12 phenotypes related to fat deposition and fatty acid composition, we observed that the UTS2 gene was significantly associated with the amount of skeletal saturated fatty acids, while its receptor (UTS2R) gene had significant effects on amounts of saturated and monounsaturated fatty acids, Δ 9 desaturase activity for converting 16:0 into 16:1, muscle fat (marbling) score and Longissimus Dorsi muscle area. However, in this population, these markers were not associated with subcutaneous fat depth or percent kidney, pelvic and heart fat. We also found that mutations in the promoter regions altered the promoter activities in both genes and coding SNPs might affect the mRNA stability in the UTS2R gene. Overall, our present study provides the first evidence that both UTS2 and UTS2R genes regulate skeletal muscle fat accumulation and fatty acid metabolism, thus indicating their potential pathological functions related to obesity and T2DM in humans.

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“…Similarly, CRFR1 and CRFR2 polymorphisms have been implicated in a variety of conditions including, asthma, obesity, depression, and alcoholism (Tantisira et al, 2004; Jiang et al, 2006; De Luca et al, 2007; Nelson et al, 2010). A clinical study evaluating the genotype of patients presenting with auditory deficits has yet to be performed to determine if CRFR1 and CRFR2 polymorphisms show any correlation with abnormal auditory function.…”

Section: Relevance Of Cochlear Hpa-equivalent Signaling To Human Disomentioning

confidence: 99%

The Cochlear CRF Signaling Systems and their Mechanisms of Action in Modulating Cochlear Sensitivity and Protection Against Trauma

et al. 2011

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A key requirement for encoding the auditory environment is the ability to dynamically alter cochlear sensitivity. However, merely attaining a steady state of maximal sensitivity is not a viable solution since the sensory cells and ganglion cells of the cochlea are prone to damage following exposure to loud sound. Most often, such damage is via initial metabolic insult that can lead to cellular death. Thus, establishing the highest sensitivity must be balanced with protection against cellular metabolic damage that can lead to loss of hair cells and ganglion cells, resulting in loss of frequency representation. While feedback mechanisms are known to exist in the cochlea that alter sensitivity, they respond only after stimulus encoding, allowing potentially damaging sounds to impact the inner ear at times coincident with increased sensitivity. Thus, questions remain concerning the endogenous signaling systems involved in dynamic modulation of cochlear sensitivity and protection against metabolic stress. Understanding endogenous signaling systems involved in cochlear protection may lead to new strategies and therapies for prevention of cochlear damage and consequent hearing loss. We have recently discovered a novel cochlear signaling system that is molecularly equivalent to the classic hypothalamic-pituitary-adrenal (HPA) axis. This cochlear HPA-equivalent system functions to balance auditory sensitivity and susceptibility to noise-induced hearing loss, and also protects against cellular metabolic insults resulting from exposures to ototoxic drugs. We review the anatomy, physiology, and cellular signaling of this system, and compare it to similar signaling in other organs/tissues of the body.

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Cross Species Association Examination of UCN3 and CRHR2 as Potential Pharmacological Targets for Antiobesity Drugs

Cited by 18 publications

References 23 publications

Genes involved in muscle lipid composition in 15 European Bos taurus breeds

Genes involved in muscle lipid composition in 15 European Bos taurus breeds

Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus

The Cochlear CRF Signaling Systems and their Mechanisms of Action in Modulating Cochlear Sensitivity and Protection Against Trauma

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