• Title/Summary/Keyword: 14-3-3 gamma

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TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways

  • Jung, Jong Gab;Yi, Sang-A;Choi, Sung-E;Kang, Yup;Kim, Tae Ho;Jeon, Ja Young;Bae, Myung Ae;Ahn, Jin Hee;Jeong, Hana;Hwang, Eun Sook;Lee, Kwan-Woo
    • Molecules and Cells
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    • v.38 no.12
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    • pp.1037-1043
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    • 2015
  • The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. 1 TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-$phosphoelF2{\alpha}$-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance.

Management and Outcome of Intracranial Dural Arteriovenous Fistulas That Have Caused a Hemorrhage in the Posterior Fossa : A Clinical Study

  • Rifat Akdag;Ugur Soylu;Ergun Daglioglu;Ilkay Akmangit;Vedat Acik;Ahmet Deniz Belen
    • Journal of Korean Neurosurgical Society
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    • v.66 no.6
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    • pp.672-680
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    • 2023
  • Objective : We evaluated the diagnosis, treatment, and long-term results of patients with dural arteriovenous fistula (dAVF), which is a very rare cause of posterior fossa hemorrhage. Methods : This study included 15 patients who underwent endovascular, surgical, combined, or Gamma Knife treatments between 2012 and 2020. Demographics and clinical features, angiographic features, treatment modalities, and outcomes were analyzed. Results : The mean age of the patients was 40±17 years (range, 17-68), and 68% were men (11/15). Seven of the patients (46.6%) were in the age group of 50 years and older. While the mean Glasgow coma scale was 11.5±3.9 (range, 4-15), 46.3% presented with headache and 53.7% had stupor/coma. Four patients (26.6%) had only cerebellar hematoma and headache. All dAVFs had cortical venous drainage. In 11 patients (73.3%), the fistula was located in the tentorium and was the most common localization. Three patients (20%) had transverse and sigmoid sinus localizations, while one patient (6.7%) had dAVF located in the foramen magnum. Eighteen sessions were performed on the patients during endovascular treatment. Sixteen sessions (88.8%) were performed with the transarterial (TA) route, one session (5.5%) with the transvenous (TV) route, and one session (5.5%) with the TA+TV route. Surgery was performed in two patients (14.2%). One patient (7.1%) passed away. While there were nine patients (64.2%) with a Rankin score between 0 and 2, the total closure rate was 69.2% in the first year of control angiograms. Conclusion : In the differential diagnosis of posterior fossa hemorrhages, the differential diagnosis of dAVFs, which is a very rare entity, should be considered, even in the middle and elderly age groups, in patients presenting with good clinical status and pure hematoma. The treatment of such patients can be done safely and effectively in a multidisciplinary manner with a good understanding of pathological vascular anatomy and appropriate endovascular treatment approaches.

Environment-wide association study of elevated liver enzymes: results from the Korean National Environmental Health Survey 2018-2022

  • Youngchan Chi;Jong-Tae Park;Sewhan Na;Kyeongmin Kwak
    • Annals of Occupational and Environmental Medicine
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    • v.35
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    • pp.27.1-27.12
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    • 2023
  • Background: Environmental exposure is characterized by low concentration, chronic, and complex exposure. Traditional epidemiological studies show limitations in reflecting these characteristics since they usually focus on a single or very limited number of exposure factors at a time. In this study, we adopted the methodology of environment-wide association study (EWAS) to figure out the association of human liver function with various environmentally hazardous substances. Methods: We analyzed 2,961 participants from the Korean National Environmental Health Survey Cycle 4 (2018-2020). Using generalized linear model (GLM) analysis, we analyzed the association of 72 variables with 3 liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma glutamyl transferase [GGT]). Finally, we visualized our results with Manhattan plot. Results: In GLM analysis, perfluorooctanesulfonate were positively associated with ALT (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.39-3.46; padjusted = 0.0147) and perfluorodecanoic acid showed positive association with GGT (OR: 2.73; 95% CI: 1.36-5.5; padjusted = 0.0256). Plasma mercury showed positive association with GGT (OR: 1.45; 95% CI: 1.14-1.84; padjusted = 0.0315). Using a plastic container while keeping food in the refrigerator was associated with elevated GGT compared to using a glass container (OR: 1.51; 95% CI: 1.16-1.95; padjusted = 0.0153). 2-ethyl-5-oxohexyl phthalate, showed a negative trend with all 3 indices, with AST (OR: 0.54; 95% CI: 0.39-0.73; padjusted = 0.00357), ALT (OR: 0.5; 95% CI: 0.34-0.75; padjusted = 0.036), GGT (OR: 0.55; 95% CI: 0.4-0.76; padjusted = 0.00697). Bisphenol S and frequent use of sunblock cream showed negative association with ALT (OR: 0.77; 95% CI: 0.66-0.89), and GGT (OR: 0.25; 95% CI: 0.11-0.55), respectively. Conclusions: We conducted an exploratory study on environmental exposure and human liver function. By using EWAS methodology, we identified 7 factors that could have potential association with liver function.

Use of Auxins for Rhizome Propagation and Shading Effect on Growth of Asarum sieboldii Mio. (세신(細辛)의 근경삽(根莖揷)번식에 있어서 오옥신의 이용과 차광재배(遮光栽培))

  • Kim, Sun-Gon;Park, Chung-Heon;Choi, Dong-Geun;Hwang, Chang-Ju;Chin, Seong-Kye
    • Korean Journal of Medicinal Crop Science
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    • v.2 no.3
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    • pp.198-204
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    • 1994
  • This study was carried out to investigate the auxin(IAA, IBA, NAA) treatment and the effect of shading rate in Asarum sieboldii. The results obtained were summerized as follows: By the soaking treatment of auxins to the cutted rhizome enhanced root growth and plant weight. By the increment of shading rate, plant growth was much better compare to the control. Leaf fallen times appeared about 20 days more earlier at plain area then the alpain area. Root yield was much higher by the treatment of shading then the conventional cultivation so it seem to be the useful for large scale cultivations of A. sieboldii.

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Effects of Feeding Herbaceous Peat on Growth Performance and Meat Quality of Holstein Beef Cattle (허브부식토 급여가 비육우의 증체 및 육질개선에 미치는 영향)

  • Kim, Hong-Yun;Park, Joong-Kook;Ahn, Jong-Ho
    • Korean Journal of Organic Agriculture
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    • v.21 no.1
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    • pp.79-93
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    • 2013
  • The experiment was conducted to investigate the effects of feeding herbaceous peat on growth performance and meat quality of Holstein beef cattle. Total of 20 Holstein beef cattle (18~20 month of age, $657{\pm}31kg$ body weight) were conventionally and separately fed a concentrate diet and rice straw for 134 days. The dietary treatments were randomly assigned by complete block design into four treatments, each of which were five heads in early fattening stage. The treatments in this study were the control group fed basal diet, feeding herbaceous peat group (5%/diet, T1), feeding coated vitamin C group (20g/head, T2) and feeding mixture of herbaceous peat and coated vitamin C group (5%/diet+20g/head, T3). The initial body weights between the groups of control, T1, T2 and T3 were similar showing with $689{\pm}31$, $661{\pm}24$, $659{\pm}32$ and $622{\pm}19kg$. The daily body weight gain was higher in T3 by 8.3% than that in the control (p<0.05). Glucose concentration in control group was the highest among treatments (p<0.05), but there was no significant differences between treatments on AST (aspartate aminotransferase), ALT (alanine aminotransferase), BUN and total protein concentrations of blood. The fat content of sirloin in the T2 was significantly higher than control and T1 group (p<0.05). Meat color (CIE) values in T2 was the highest among treatments (p<0.05), and other treatments also increased those values. In overall, the feeding herbaceous peat and vitamin C to the Holstein beef cattle was considered to have positive effects on the growth performance of Holstein beef cattle. In addition, the effects on the performances of animals were more improved when fed herbaceous peat and vitamin C concurrently.

Effects of a Diet Supplemented with Dried Animal Blood and Macsumsuk Mixture on the Growth Performance and Meat Quality Parameters of Broiler Chickens (맥섬석 혼합 건조혈분 급여가 육계의 생산성과 육질에 미치는 영향)

  • Kim, Byung-Ki;Yi, Jun-Koo;Hwang, Eun-Gyeong;Kang, Bo-Seok
    • Korean Journal of Poultry Science
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    • v.44 no.1
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    • pp.29-39
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    • 2017
  • This study examined the effects of adding dried blood mixed with Macsumsuk to the feed of broiler chickens. The blood had been dried at $200^{\circ}C$ in an ultra-high-temperature injection system and mixed in a 70:30 proportion of blood meal to Macsumsuk. The experiment consisted of four treatment groups of 150 chickens each. The control group received common broiler feed only, while treatment groups T1, T2, and T3 received feed supplemented with 0.5, 1.0, and 3.0% of the blood meal/Macsumsuk mixture, respectively. The diets were fed for a total of 35 days. Compared with the controls, body weight gain was improved in groups T1 (1,621 g), T2 (1,749 g), and T3 (1,739 g) (1,621-1,749 g vs. 1,448.5 g, respectively) and feed efficiency increased (p<0.01). The carcass rate in group T3 was higher by 83.26% than that in the controls (75.96 %) (p<0.01). The water holding capacity (WHC) increased in groups T1 and T2 (62.27 and 63.80% respectively) compared with controls (p<0.01). The intestine length was longer in groups T1 and T2 (53.98-55.48) than in controls (45.81) (p<0.01). Adding 0.5-1.0% of the dried blood meal Macsumsuk supplement resulted in a significant reduction in the cholesterol content (39.28~47.34 mg/100 g) compared with the controls (50.44 mg/100 g) (p<0.001); furthermore, the proportions of fatty acids including oleic (C18:1n9), ${\gamma}-linoleic$ (C18:3n6), eicosenoic (C20:1n9), and arachidonic (C20:4n6) acids were significantly increased (p<0.01). Compared with controls, the proportion of unsaturated fatty acids (UFA), mono-unsaturated fatty acids (MUFA), and proportion of UFA / SFA in group T1 was (68.66 vs. 69.35%, 51.22 vs 52.00%, and 2.19 vs. 2.26%, respectively) (p<0.05). However, the amino acid content of cystine and methionine of the treatment group (0.43~0.57%) was significantly higher than that of controls (0.38~0.46%) (p<0.05). Overall, supplementing the feed with 0.5-1.0% of the mixture of blood meal Macsumsuk improved productivity by increasing weight gain and feed efficiency, improved meat quality by increasing the water-holding capacity and levels of unsaturated fatty acids, and improved meat color.

Research on The Utility of Acquisition of Oblique Views of Bilateral Orbit During the Dacryoscintigraphy (눈물길 조영검사 시 양측 안 와 사위 상 획득의 유용성에 대한 연구)

  • Park, Jwa-Woo;Lee, Bum-Hee;Park, Seung-Hwan;Park, Su-Young;Jung, Chan-Wook;Ryu, Hyung-Gi;Kim, Ho-Shin
    • The Korean Journal of Nuclear Medicine Technology
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    • v.18 no.1
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    • pp.76-81
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    • 2014
  • Purpose: Diversity and the lachrymal duct deformities and the passage inside the nasal cavity except for anterior image such as epiphora happens during the test were able to express more precisely during the dacryoscintigraphy. Also, we thought about the necessity of a method to classify the passage into the naso-lachrymal duct from epiphora. Therefore, we are to find the validity of the method to obtain both oblique views except for anterior views. Materials and Methods: The targets of this research are 78 patients with epiphora due to the blockage at the lachrymal duct from January 2013 to August 2013. Average age was $56.96{\pm}13.36$. By using a micropipette, we dropped 1-2 drops of $^{99m}TcO4^-$ of 3.7 MBq (0.1 mCi) with $10{\mu}L$ of each drop into the inferior conjunctival fold, then we performed dynamic check for 20 minutes with 20 frames of each minute. In case of we checked the passage from both eyes to nasal cavity immediately after the dynamic check, we obtained oblique view immediately. If we didn't see the passage in either side of the orbit, we obtained oblique views of the orbit after checking the frontal film in 40 minutes. The instrument we used was Pin-hole Collimator with Gamma Camera(Siemens Orbiter, Hoffman Estates, IL, USA). Results: Among the 78 patients with dacryoscintigraphy, 35 patients were confirmed with passage into the nasal cavity from the anterior view. Among those 35 patients, 15 patients were confirmed with passage into the nasal cavity on both eyes, and it was able to observe better passage patterns through oblique view with a result of 8 on both eyes, 2 on left eye, and 1 on right eye. 20 patients had passage in left eye or right eye, among those patients 10 patients showed clear passage compared to the anterior view. 13 patients had possible passage, and 30 patients had no proof of motion of the tracer. To sum up, 21 patients (60%) among 35 patients showed clear pattern of passage with additional oblique views compared to anterior view. People responded obtaining oblique views though 5 points scale about the utility of passage identification helps make diagnoses the passage, passage delayed, and blockage of naso-lachrymal duct by showing the well-seen portions from anterior view. Also, when classifying passage to naso-lachrymal duct and flow to the skin, oblique views has higher chance of classification in case of epiphora (anterior:$4.14{\pm}0.3$, oblique:$4.55{\pm}0.4$). Conclusion: It is considered that if you obtain oblique views of the bilateral orbits in addition to anterior view during the dacryoscintigraphy, the ability of diagnose for reading will become higher because you will be able to see the areas that you could not observe from the anterior view so that you can see if it emitted after the naso-lachrymal duct and the flow of epiphora on the skin.

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The Role of c-Jun N-terminal Kinase in the Radiation-Induced Lung Fibrosis (방사선에 의한 폐 섬유화증에서 c-Jun N-terminal Kinase(JNK)의 역할)

  • Uh, Soo-Taek;Hong, Ki-Young;Lee, Young-Mok;Kim, Ki-Up;Kim, Do-Jin;Moon, Seung-Hyuk;Kim, Yong-Hoon;Park, Choon-Sik;Yeom, Uk;Kim, Eun-Suk;Choi, Doo-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.4
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    • pp.450-461
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    • 2001
  • Background : The underlying pathogenesis of radiation-induced lung fibrosis (RTLF) has not been very well defined. However, the role of TGF-$\beta$ in the generation of RTLF has been a major focus because there is an increase in the expression of both the TGF-${\beta}m$-RNA and its protein preceding RTLF lesions. The down stream signal after a TGF-$\beta$ stimulated lung fibrosis includes the activation of many mediators such as Smad and c-Jun N-terminal kinase (JNK) through TAK1. It is we hypothesized that JNK activation may play a pivotal role in RTLF pathogenesis through increased transcription of the fibrogenic cytokines. The present study evaluates JNK activity in alveolar macrophages after irradiation and the relationship between JNK activity and the amount of collagen in the lung tissues. Methods : C57BL/6 mice(20-25 gr, males) received chlorotetracycline(2g/L) in their drinking water 1 week prior to irradiation and continuously there after. The mice were irradiated once with 1400 cGy of $60CO{\gamma}$-ray over the whole chest. The cellular composition of the whole lung bronchoalveoalr lavage fluids(BALF), elastin expression in the lung tissues, the level of hydroxyproline in lung tissues, and an in vitro JNK assay was measured before irradiation and one, four, and eight weeks after irradiation (RT). Results : The volumes of BALF retrieved from instilled 4 mL of saline with 2% heparin were 3.7-3.8 mL for each group. The cell numbers were similar before($4.1{\times}10^4{\pm}0.5{\times}10^4/mL$) and 1 week($3.1{\times}10^4{\pm}0.5{\times}10^4/mL$) after RT. At four and eight weeks after RT, the cell number reached to $14.0{\times}10^4{\pm}1.5{\times}10^4mL$ and $10.0{\times}10^4{\pm}1.3{\times}10^4/mL$, respectively. There we no changes in the lymphocytes and neutrophils population observed in the BALF after RT. The H-E stain of the lung tissues did not show any structural and fibrotic change in the lung tissues at 4 and 8 weeks after RT. In addition, the amount of elastin and collagen were not different on Verhoeff staining of the lung tissues before RT to eight weeks after RT. The hydroxyproine content was measured with the left lung dissected from the left main bronchus. The lung were homogenized and hydrolyzed with 6 N Hel for 12 hours at $110^{\circ}C$ then measured as previously described. The content of hydroxyproline, standardized with a lung protein concentration, reached a peak 4 weeks after RT, and thereafter showed a plateau. AnIn vitro JNK assay using c-$Jun_{1-79}$-GST sepharose beads were performed with the alveolar macrophages obtained from the BAL. JNK activity was not detected prior to RT, However, the JNK activity increased from one week after RT and reached a peak four weeks after RT. Conclusion : JNK may be involved in the pathogenesis because the JNK activity showed similar pattern observed with the hydroxyproine content. However, it is necessary to clarify that the JNK increases the transcription of fibrogenic cyiokines through the transcription factor.

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The Effect of Weight Ratio of Carbon Source to Nitrogen Source on toe Growth and the Composition of Fatty Acid of Thraustochytrium aureum ATCC 34304 (탄소원과 질소원의 무게비가 Thraustochytrium aureum ATCC 34304의 성장 및 지방산 조성 특성에 미치는 영향)

  • Kim Won-Ho;Park Seung-Hye;Song Sang-Kyu;Bae Kyung-Dong;Hur Byung-Ki
    • KSBB Journal
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    • v.20 no.4
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    • pp.266-270
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    • 2005
  • The effect of the weight ratio of carbon source to nitrogen source on the growth and the composition change of fatty acids of Thraustochytrium aureum ATCC 34304 was investigated. The cell concentration of 5 days' culture increased and then decreased according to the increase of C/N, The ratioes for the maximum biomass were unique respectively and distributed between 1 and 4 with the initial sugar concentration in the range of 5 g/L to 25 g/L. The biomass yield, $Y_{x/s}$ decreased along with the increase of C/N, but maintained a constant value 0.35 between 10 and 20. The composition of myristic acid $(C_{14:0})$, one component of the lipid synthesized by T. aureum, was not affected with the change of C/N, but the composition of palmitic acid $(C_{16:0})$ was around $20\%$ below 4 of C/N and decreased to $15\%$ according to C/N about 4. The compositions of oleic acid $(C_{18:1})$ and linoleic acid $(C_{18:2})$ increased from 0 to $20\%\;and\;7\%$ respectively. The composition of $\gamma-linoleic$ acid $(C_{18:3})$, however, reduced from $5\%\;to\;2\%$. EPA $(C_{20:5})$ and DPA $(C_{22:5})$ showed a tendency of reduction in the weight composition according to the increase of C/N, but DHA $(C_{22:6})$ had a trend maintaining an approximately constant value, around $40\%$, irrespective of the change of C/N.

Genetic characterisation of PPARG, CEBPA and RXRA, and their influence on meat quality traits in cattle

  • Goszczynski, Daniel Estanislao;Mazzucco, Juliana Papaleo;Ripoli, Maria Veronica;Villarreal, Edgardo Leopoldo;Rogberg-Munoz, Andres;Mezzadra, Carlos Alberto;Melucci, Lilia Magdalena;Giovambattista, Guillermo
    • Journal of Animal Science and Technology
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    • v.58 no.4
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    • pp.14.1-14.9
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    • 2016
  • Background: Peroxisome proliferator-activated receptor gamma (PPARG), CCAAT/enhancer binding protein alpha (CEBPA) and retinoid X receptor alpha (RXRA) are nuclear transcription factors that play important roles in regulation of adipogenesis and fat deposition. The objectives of this study were to characterise the variability of these three candidate genes in a mixed sample panel composed of several cattle breeds with different meat quality, validate single nucleotide polymorphisms (SNPs) in a local crossbred population (Angus - Hereford - Limousin) and evaluate their effects on meat quality traits (backfat thickness, intramuscular fat content and fatty acid composition), supporting the association tests with bioinformatic predictive studies. Results: Globally, nine SNPs were detected in the PPARG and CEBPA genes within our mixed panel, including a novel SNP in the latter. Three of these nine, along with seven other SNPs selected from the Single Nucleotide Polymorphism database (SNPdb), including SNPs in the RXRA gene, were validated in the crossbred population (N = 260). After validation, five of these SNPs were evaluated for genotype effects on fatty acid content and composition. Significant effects were observed on backfat thickness and different fatty acid contents (P < 0.05). Some of these SNPs caused slight differences in mRNA structure stability and/or putative binding sites for proteins. Conclusions: PPARG and CEBPA showed low to moderate variability in our sample panel. Variations in these genes, along with RXRA, may explain part of the genetic variation in fat content and composition. Our results may contribute to knowledge about genetic variation in meat quality traits in cattle and should be evaluated in larger independent populations.