Obesidade genética não sindrômica: histórico, fisiopatologia e principais genes / Non-syndromic genetic obesity: history, pathophysiology and key genes

A obesidade é definida pelo excesso de gordura corporal acumulada no tecido adiposo quando o indivíduo atinge valores de IMC igual ou superior a 30 Kg/m2. Constitui um dos principais fatores de risco para várias doenças não transmissíveis (DNTs) como por exemplo, diabetes mellitus tipo 2 (DM2), doenças cardiovasculares, hipertensão arterial, acidente vascular cerebral e até mesmo o câncer. Embora a obesidade esteja diretamente relacionada com o consumo calórico excessivo em relação ao gasto energético diário, sua etiologia pode estar associada aos baixos níveis de atividade física, às alterações neuroendócrinas e aos fatores genéticos. Considerando o componente genético, esta pode ser classificada como sindrômicas e estar associada às alterações cromossômicas estruturais ou numéricas, ou como não sindrômica, quando relacionada, principalmente, com os polimorfismos de nucleotídeos simples (SNPs) em alelos que atuam como herança monogênica, ou ainda com a interação vários genes (poligênica multifatorial). Apesar de existirem muitas etiologias diferentes, normalmente a obesidade é tratada a partir da mesma abordagem, desconsiderando a fisiologia que a desencadeou. Dessa forma, o objetivo do presente trabalho foi abordar a obesidade genética não sindrômica por meio a) da descrição breve de perspectiva histórica sobre seu entendimento; b) da exposição dos principais mecanismos moleculares envolvidos com o controle de peso; c) da compilação dos principais genes e SNPs relacionados; d) da definição dos principais genes; e e) da abordagem das principais perspectivas de intervenção.

Obesity is defined as excess body fat accumulated in the adipose tissue when the individual reaches BMI values equal to or greater than 30 kg/m2. It is one of the main risk factors for several non-communicable diseases (NCDs), such as Type 2 Diabetes mellitus (T2D), cardiovascular diseases, high blood pressure, stroke and even cancer. Although obesity is directly related to excessive calorie intake in relation to daily energy expenditure, its etiology may be associated with low levels of physical activity, neuroendocrine changes, and genetic factors. Considering the genetic component, it can be classified as syndromic and be associated with chromosomal or numerical changes, or as non-syndromic and being related mainly to single nucleotide polymorphisms (SNPs) in alleles that act as monogenic inheritance, or with an interaction of several genes (multifactorial polygenic). Although there are many different etiologies, obesity is usually treated using the same approach, disregarding the physiology that triggered it. Thus, the aim of this study was to address non-syndromic genetic obesity through a) a brief description of a historical perspective on its understanding; b) the exposure of the main molecular mechanisms involved in weight control, c) the compilation of the key genes and related SNPs, d) the definition of the key genes and e) the approach of the main intervention representations.

Association of leptin and leptin receptor polymorphisms with coronary artery disease in a North Chinese Han population

Abstract INTRODUCTION: Leptin (LEP) is a peptide hormone that acts via leptin receptor (LEPR) binding. Genetic evidence from different human populations has implicated LEP/LEPR in the pathogenesis of coronary artery disease (CAD), and suggests that certain LEP/LEPR gene polymorphisms may increase the risk of CAD. The aim of this study was to assess two single nucleotide polymorphisms (SNPs) in LEP genes (rs2167270 and rs7799039) and two in LEPR genes (rs6588147, rs1137100) for association with CAD. METHODS: We enrolled 271 North Chinese Han CAD patients, and 113 healthy age- and sex-matched controls. Genomic DNA was extracted from whole blood, and the four SNPs were assessed using a MassArray system. RESULTS: The G allele frequency at rs2167270 was significantly higher among CAD cases than among controls. The AG genotype at rs7799039 was associated with a significantly decreased risk of CAD unlike the AA genotype used as the reference. The A allele was significantly associated with the CAD patient group. Interestingly, statistically significant differences in genotype and allele frequency at LEP rs2167270 and rs7799039 existed among females but not among males. CONCLUSIONS: The current study detected a significant association between genetic variations at LEP rs7799039 and rs2167270 and the risk of CAD in a north Chinese population, and revealed that LEP rs2167270 and rs7799039 gene polymorphisms might act as predisposing factors for CAD.

LEPR polymorphisms and haplotypes in Mexican patients with colorectal cancer / Polimorfismos y haplotipos del gen LEPR en pacientes mexicanos con cáncer colorrectal

Abstract Introduction: Obesity and colorectal cancer could be linked by adipocytokines, which are proteins associated with cell proliferation. High levels of the adipocytokine leptin promote the development of colorectal cancer through its receptor. Objective: To determine the association between c.326A>G and c.668A>G LEPR gene polymorphisms and colorectal cancer. Materials and methods: DNA was extracted from the peripheral blood of 147 patients with sporadic colorectal cancer and 134 healthy people. Genotypes were obtained by PCR- RFLP and the association was determined by the odds ratio (OR) test using the SPSS™, version 10.0, program. Haplotype frequencies and linkage disequilibrium were estimated by the Arlequin, version 3.5, software. Results: Both polymorphisms were in Hardy-Weinberg equilibrium. Only the c.326A>G heterozygous genotype revealed an increased risk for colorectal cancer development (OR=1.81, 95% CI=1.04-3.16, p=0.04). The AG haplotype showed a significant association with colorectal cancer (OR=0.58, 95% CI=0.35-0.96, p<0.03). Linkage disequilibrium between the variants was only evident for the patients group (r2=0.36). Conclusion: Our results suggest that AG individuals heterozygous for the c.326A>G LEPR variant have a higher risk of colorectal cancer development whereas the AG haplotype (c.326A/c.668G) has a protective effect in the Mexican population.

Resumen Introducción. La relación entre la obesidad y el cáncer colorrectal podría estar dada por las adipocitocinas, proteínas asociadas con la proliferación celular. Los niveles elevados de la adipocitocina leptina promueven el desarrollo del cáncer colorrectal a través de su receptor. Objetivo. Determinar la asociación de los polimorfismos c.326A>G y c.668A>G del gen LEPR con el cáncer colorrectal. Materiales y métodos. A partir de sangre periférica, se extrajo el ADN de 147 pacientes con cáncer colorrectal esporádico y de 134 personas sanas. La genotipificación se hizo mediante PCR-RFLP y la asociación se determinó por la odds ratio (OR) en el programa SPSS™, versión 10.0. Las frecuencias haplotípicas y el desequilibrio de ligamiento se estimaron utilizando el programa Arlequin, versión 3.5. Resultados. Ambos polimorfismos estaban en equilibrio de Hardy-Weinberg. Solo el genotipo heterocigoto c.326A>G reveló un mayor riesgo de desarrollar cáncer colorrectal (OR=1,81; IC95% 1,04-3,16; p=0,04). El haplotipo AG mostró una asociación significativa con este cáncer (OR=0,58; IC95% 0,35-0,96; p≤0,03) y el desequilibrio de ligamiento entre las variantes fue evidente únicamente en el grupo de pacientes (r2=0,36). Conclusión. Los resultados sugieren que los individuos heterocigotos con el haplotipo AG para la variante c.326A>G en el gen LEPR tenían un mayor riesgo de desarrollar cáncer colorrectal, en tanto que el haplotipo AG (c.326A/c.668G) tenía un efecto protector en la población mexicana.

Obesidad monogénica / Monogenic obesity

La obesidad infantil es un problema creciente de salud, asociado con una significativa morbilidad física y psicológica a edades tempranas. La obesidad es una enfermedad multifactorial, causada en la mayoría de los casos por la interacción de determinados polimorfismos genéticos con el medio ambiente. Solo en un 5 % resulta de mutaciones en genes específicos, originando en algunos casos síndromes mendelianos de muy escasa incidencia en la población que se clasifican como obesidades monogenicas. La mayoría de estos genes están implicados en la regulación del hambre-saciedad en el sistema nervioso central, en el cual el eje de leptina-melanocortina desempeña un rol fundamental. Se presentan clínicamente como formas de obesidad de inicio precoz, severas, que se asocian con trastornos de la conducta alimentaria y alteraciones endocrinológicas. La mutación en el gen del receptor melanocortina-4 (MC4R) es la causa más común de obesidad monogénica grave de aparición temprana. El objetivo de esta revisión es realizar una actualización sobre las obesidades de inicio precoz de causa monogénicas, su etiopatogenia, sus principales características clínicas y su abordaje terapéutico. El manejo de estos pacientes aún es un reto, ya que el tratamiento específico solo se encuentra disponible en un solo tipo de obesidad monogénica. Para el resto de los tipos se encuentran en investigación nuevas moléculas que actúan sobre la vía leptina-melanocortina

Childhood obesity is a growing health problem associated with significant physical and psychological morbidity at an early age. Obesity is a multifactorial disease in the majority of cases caused by an interaction of certain genetic polymorphisms and the environment. In only 5% of the patients it is related to specific gene mutations in some cases resulting in very rare Mendelian syndromes classified as monogenic obesity. The majority of these genes are involved in the hunger-satiety regulation in the central nervous system, in which the leptin-melanocortin axis plays a fundamental role. Clinically, these forms of obesity present at an early age, are severe, and are associated with eating disorders and endocrine alterations. A mutation in the melanocortine-4 receptor (MC4R) gene is the most common cause of early-onset severe monogenic obesity. The aim of this review was to provide an update of the different forms of early-onset monogenic obesity, focusing on the etiopathogenicity, main clinical features, and therapeutic approach. The management of these patients is still a challenge as specific treatment is only available for one type of monogenic obesity. For the remaining types new molecules that act on the leptin-melanocortin pathway are currently being investigated

Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7L2 in gestational diabetes in a Brazilian population

ABSTRACT Objective Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. Subjects and methods 252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age. The polymorphisms were genotyped using fluorescent probes (TaqMan®). Results All groups were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms did not show significant differences between the groups (P > 0.05). In the healthy and GDM groups, the C allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31-43%] and 35.0% [29-41%]; the G allele frequencies (95% CI) of the LEPR rs1137100 polymorphism were 24.8% [19-30%] and 22.8% [18-28%]; the G allele frequencies (95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37-50%] and 42.9% [37-49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were 7.6% [4-11%] and 8.3% [5-12%]; and the C allele frequencies (95% CI) of the TCF7L2 rs7901695 polymorphism were 33.6% [28-39%] and 39.0% [33-45%], respectively. Conclusion The studied polymorphisms were not associated with GDM in a Brazilian population.

Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals / Polimorfismos no gene do receptor de leptina são associados com adiposidade e alterações metabólicas em indivíduos brasileiros

OBJECTIVE: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. SUBJECTS AND METHODS: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G>A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. RESULTS: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95%CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). CONCLUSIONS: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.

OBJETIVO: O estudo teve por objetivo investigar a influência de polimorfismos nos genes da leptina (LEP) e do receptor de leptina (LEPR) na adiposidade e em marcadores metabólicos, como leptina, glicose e lipí­deos, em uma amostra de nossa população. SUJEITOS E MÉTODOS: Um grupo de 326 indivíduos com idade de 30 a 80 anos, 87 homens e 239 mulheres, 148 obesos e 178 não obesos, e de etnia branca foi selecionado aleatoriamente em dois hospitais clínicos da cidade de São Paulo, Brasil. Medidas antropométricas, índice de massa corporal (IMC) e gordura corporal foram avaliados. Amostras de sangue foram obtidas para extração de DNA e determinações de leptina, receptor de leptina solúvel, glicose e lipídeos. Os polimorfismos LEP -2548G>A e LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) e Lys656Asn (c.1968G>C) foram detectados por PCR-RFLP. RESULTADOS: Leptina e lipídeos séricos aumentados e LEPR Arg223Arg (genótipo GG) foram associados com maior risco de obesidade (p < 0,05), enquanto foi encontrado risco reduzido de obesidade, em portadores de LEPR Arg109Arg (genótipo GG) (OR: 0,38, 95%CI: 0,19-0,77, p = 0,007). A análise de regressão linear múltipla mostrou relação entre o alelo LEPR 223Arg e circunferência abdominal e leptinemia aumentadas (p < 0,05), enquanto o alelo LEPR 109Arg foi associado com aumento de colesterol total e triglicerídeos (p < 0,05). Os portadores do haplotipo 3 do LEPR (AGG: 109Lys/233Arg/656Lys) tiveram maior risco aumentado para obesidade (OR: 2.56, 95% CI: 1.19-5.49, p = 0,017). Além disso, esse haplótipo foi associado com IMC, circunferência abdominal e leptinemia aumentados (p < 0,05). CONCLUSÕES: Polimorfismos de LEPR são associados com obesidade, hiperleptinemia e perfil lipídico aterogênico sugerindo seu papel potencial para a resistência à leptina e risco cardiovascular.

Polymorphisms in LEPR, PPARG and APM1 genes: associations with energy intake and metabolic traits in young children / Polimorfismos nos genes LEPR, PPARG e APM1: associações com ingestão energética e parâmetros metabólicos em crianças em idade precoce

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) in five genes - leptin, leptin receptor (LEPR), adiponectin (APM1), peroxisome proliferator-activated receptor gamma (PPARG) and uncoupling protein 1 - with anthropometric, metabolic, and dietary parameters in a Southern Brazilian cohort of 325 children followed up from birth to 4 years old. MATERIALS AND METHODS: SNPs were analyzed using polymerase chain reaction-based procedures, and their association with phenotypes was evaluated by t-test, analysis of variance, and general linear models. RESULTS: LEPR223Arg allele (rs1137101) was associated with higher daily energy intake at 4 years of age (P = 0.002; Pcorrected = 0.024). PPARG 12Ala-carriers (rs1801282) presented higher glucose levels than Pro/Pro homozygotes (P = 0.007; Pcorrected = 0.042). CONCLUSIONS: Two of the six studied SNPs presented consistent associations, showing that it is already possible to detect the influences of genetic variants on susceptibility to overweight in 4-year-old children.

OBJETIVO: Avaliar a associação de polimorfismos de nucleotídeo único (SNPs) em cinco genes: leptina, receptor da leptina (LEPR), adiponectina (APM1), receptor ativado por proliferadores de peroxissomas gama (PPARG) e proteína desacopladora 1 com parâmetros antropométricos, metabólicos e dietéticos em uma coorte sul-brasileira composta por 325 crianças acompanhadas desde o nascimento até os 4 anos. MATERIAIS E MÉTODOS: Os SNPs foram analisados por meio da reação em cadeia da polimerase e sua associação com os fenótipos foi avaliada utilizando teste T, análise de variância e análise fatorial. RESULTADOS: O alelo LEPR223Arg (rs1137101) foi associado a uma maior ingestão energética diária aos 4 anos (P = 0,002; Pcorrigido = 0,024). Os portadores do alelo PPARG12Ala (rs1801282) apresentaram maior glicemia em relação aos homozigotos Pro/Pro (P = 0,007; Pcorrigido = 0,042). CONCLUSÕES: Dois dos seis SNPs estudados apresentaram associações consistentes, mostrando que aos 4 anos de idade já é possível detectar as influências de variantes genéticas sobre a suscetibilidade ao excesso de peso.

Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

Lack of mutations in the leptin receptor gene in severely obese children / Ausência de mutação no gene receptor de leptina em crianças gravemente obesas

OBJECTIVE: To analyze the LEPR gene in obese children and to investigate the associations between molecular findings and anthropometric and metabolic features. SUBJECTS AND METHODS: Thirty-two patients were evaluated regarding anthropometric characteristics, blood pressure, heart rate, serum glucose, insulin, leptin levels, and lipid profile. The molecular study consisted of the amplification and automatic sequencing of the coding region of LEPR in order to investigate new mutations. RESULTS: We identified a high prevalence of metabolic disorders: impaired fasting glucose in 12.5% of the patients, elevated HOMA-IR in 85.7%, low HDL-cholesterol levels in 46.9%, high triglyceride levels in 40.6%, and hypertension in 58.6% of the patients. The molecular study identified 6 already described allelic variants: rs1137100 (exon-2), rs1137101 (exon-4), rs1805134 (exon-7), rs8179183 (exon-12), rs1805096 (exon-18), and the deletion/insertion of the pentanucleotide CTTTA at 3'untranslated region. CONCLUSIONS: The frequency of alleles observed in this cohort is similar to that described in the literature, and was not correlated with any clinical feature. The molecular findings in the analysis of the LEPR did not seem to be implicated in the etiology of obesity in these patients.

OBJETIVO: Analisar o LEPR em crianças obesas e investigar associações entre achados moleculares e características antropométricas e metabólicas. SUJEITOS E MÉTODOS: Foram avaliados 32 pacientes quanto às características antropométricas, à pressão arterial, à frequência cardíaca, às dosagens séricas de glicemia, à insulina, à leptina e ao perfil lipídico. O estudo molecular consistiu na amplificação e no sequenciamento automático da região codificadora do LEPR para pesquisar mutações. RESULTADOS: Identificou-se uma alta prevalência de distúrbios metabólicos: glicemia de jejum alterada em 12,5%, HOMA-IR elevado em 85,7%, níveis de HDL-colesterol baixos em 46,9%, níveis de triglicérides elevados em 40,6% e hipertensão arterial em 58,6%. O estudo molecular identificou 6 variações alélicas já descritas na literatura: rs1137100 (éxon-2), rs1137101 (éxon-4), rs1805134 (éxon-7), rs8179183 (éxon-12), rs1805096 (éxon-18) e deleção/inserção do pentanucleotídeo CTTTA na região 3' não traduzida. CONCLUSÕES: A frequência das variações alélicas observada é semelhante à descrita na literatura e não se correlacionou com nenhuma característica clínica. Os resultados da análise molecular do LEPR não parecem estar implicados na etiologia da obesidade desses pacientes.

Association of polymorphisms in leptin receptor gene with obesity and type 2 diabetes in the local population of Coimbatore.

BACKGROUND: Candidate gene association studies are very relevant to the area of clinical pharmacology. As information on candidate genes and candidate single nucleotide polymorphisms increases, a number of such candidates can be studied in a population to explore their association with their susceptible disease. One such attractive and popular Single Nucleotide Polymorphism (SNP) candidate for obesity is the gene coding for leptin receptor. The leptin receptor gene (LEPR) polymorphism plays an important role in obesity and type 2 diabetes. But the role of this polymorphism is not yet studied in Indian population. Hence, the study focused to explore the association of leptin receptor polymorphisms (K109R, Q223R and K656N) with obesity and type 2 diabetes in both diabetic and non-diabetic subjects recruited from the local population of Coimbatore. MATERIALS AND METHODS: Genotypic analysis for the three polymorphisms has been made for 300 subjects (150 diabetic and 150 non-diabetic) with the age range of 40–60 years using conventional Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) techniques in a case–control fashion. Allele frequencies were estimated based on the gene count method. Correlation was made with phenotypic variables including body mass index (BMI), waist-to-hip ratio (WHR), insulin and leptin levels for those polymorphisms. RESULTS AND CONCLUSION: Among the polymorphisms tested in this study, significant association with BMI (P < 0.05), WHR (P < 0.05) leptin (P < 0.001) and insulin (P < 0.0001) was observed for the SNP Q223R, whereas in the case of the other two polymorphisms the association was not statistically significant. The significance value was calculated based on the χ2 test. The controls are also found to have a higher frequency of homozygous mutants for Q223R and are significantly associated with obesity. These findings support the hypothesis that Q223R polymorphism is associated with obesity. It can be speculated that the controls showing the same allele may develop Type 2 diabetes at a later stage and Q223R can act as a strong marker.

Frecuencia de los marcadores del gen leptina en razas bovinas criollas y colombianas: I romosinuano, chino santandereano, sanmartinero y Velásquez / Frequency of leptin gene markers in creole and colombian cattle: I romosinuano, chino santandereano, sanmartinero and Velásquez breeds

La leptina es una hormona de 146 aminoácidos, secretada al torrente sanguíneo por los adipocitos blancos. Está asociada a diferentes características productivas y reproductivas en animales de granja. Los objetivos de este trabajo fueron determinar los polimorfismos de tres marcadores moleculares del gen leptina: Un polimorfismo de un único nucleótido (SNP) y los microsatélites BM1500 (ST) en la región 3’ y un marcador de la región 5ÚTR (WD), los cuales fueron amplificados por la técnica de PCR y visualizados en geles de agarosa después de ser sometidos a restricción para el SNP y en geles de poliacrilamida para los microsatélites y establecer la asociación, mediante análisis de varianza, de estos marcadores con peso corporal, área de ojo de lomo (AOL), Espesor de Grasa Dorsal (EGD), características medidas a partir de imágenes de ultrasonido tomadas. Se muestrearon 252 animales de 3 razas criollas y una colombiana de diferentes núcleos de Colombia. Para el SNP, la mayor frecuencia del alelo T se presentó en la raza Sanmartinero (0,66) y la menor en la raza Chino Santandereano (0,23). Para el microsatélite BM 1500 (ST) se encontraron cinco alelos diferentes (136; 138; 144; 146 y 148), siendo los mas frecuentes para todas las razas 136 (entre 0,31 y 0,76) y 144 (entre 0,15 y 0,65) y para WD se identificaron 13 alelos, siendo los mas frecuentes 183 (entre 0,038 y 0,63) y 177 (entre 0,14 y 0,46). Sólo se encontró asociación en la raza Velásquez, del alelo 146 del microsatélite ST con mayor peso corporal entre los 18 y 24 meses de edad (P menor o igual que 0,05).

Leptin is a 146 amino acids hormone that it is secreted predominantly by white adipocytes. It has been associated to different productive and reproductive traits of farm’s animals. The aims of this study were to determine polymorphisms of three molecular markers of the leptin gene: A Single Nucleotide Polymorphism (SNP), the microsatellites ST (or BM1500) at the 3’UTR region, and WD at the 5’UTR. The amplification was made for PCR technique and was run in agarosa gel after the restriction for SNP and polyacrylamide gel for microsattelites. In order to establish the association of these markers with body weight, rib eyes area, and backfat thickness, Analysis of Variance (ANOVA) was used and data was obtained using ultrasound images. Samples were taken from 252 animals of three creole and one Colombian breed cattle out of different nuclei from Colombia. For the SNP, T allele frequency was larger in Sanmartinero breed and lower in Chino Santandereano breed. For the microsatellite BM 1500 five different alleles were found (136, 138, 144, 146 and 148). Among these, alleles 136 (between 0.31 y 0.76) and 144 (between 0.15 and 0.65) appeared more often. Also, in WD 13 alleles were identified, being allele 183 (between 0.038 and 0.630) and allele 177 (between 0.14 and 0.46) the most common. Finally, for the Velasquez breed the only association found occurred between the microsatellite ST allele 146 and larger body weight in individuals between 18 - 24 months (P less like 0.05).

[Detection of leptin and leptin receptor mRNA expression in the bovine testis]

Leptin, hormonal product of the ob gene, is known to regulate food intake, energy metabolism and reproductive functions in mammals. The mechanism by which leptin affect male reproductive system, in contrast to its well proven effects in female fertility, has been a matter of debate. Expression of leptin and its receptor in some reproductive organs suggest that leptin has both endocrine and paracrine/autocrine effects on reproduction. Various evidences have pointed to a direct role of leptin in the control of rodent testicular function such as steroidogenesis and spermatogenesis. So, detection of leptin and leptin receptor mRNA in bovine testis will be the first crucial step to an understanding of its paracrine/autocrine effect on testes in cattle. In the present study, we showed the expression of leptin mRNA as well as its functional receptor [Ob-Rb] mRNA in whole testis of Holstein cattle using reverse transcription and polymerase chain reaction [RT-PCR] analysis. To confirm the first results, RT-PCR products were amplified with Nested PCR using inner leptin primer pairs designed on different exons. Based on our results, although we could not determine the exact cell source of leptin in / testis, it suggests that besides its primary actions at the hypothalamic-pituitary level, leptin can also involved in autocrine and/or paracrine mechanisms in testicular physiology in cattle