Made available in DSpace on 2014-12-17T14:13:34Z (GMT). No. of bitstreams: 1 ElianaLTN_TESE.pdf: 2435421 bytes, checksum: e2270899f92315394897270d5f3384f3 (MD5) Previous issue date: 2009-10-05 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Visceral leishmaniasis (VL) has undergone changes in terms of clinical and epidemiological presentation worldwide. Urbanization has been described in different regions of Brazil and the world, as well as in the state of Rio Grande do Norte. These changes have impacted in the clinical outcome of Leishmania infection. A new clinical entity called co-infection of HIV/Leishmania has been described as a consequence of overlapping areas of occurrence of VL and HIV / AIDS in different countries including Brazil. The aim of this study was to define the process of periurbanization of the LV and describe a case series of co-infection HIV / Leishmania in Rio Grande do Norte. A new demographic pattern of VL was detected, with an increase in the number VL adult male subjects. Analysis of spatial distribution of VL in the state of Rio Grande do Norte showed that in the past 20 years VL tends to occur in larger cities and therefore the highest risk disease is greater in the eastern and western regions. The first region included Natal, the state capital, where the process of suburbanization began in 1990, and more recently the city of Mossor?, the second largest state, where periurbanization began in the last five years. In 1990, the emergence of co-infection HIV/Leishmania in the state was observed. Case-control study revealed that the new clinical entity affects adult males, who acquired HIV through sexual intercourse, 40% of those with a preivous history of leishmania infection Relapse and death from LV is increased in HIV positive compared with HIV-negative patients matched by sex and age. This pattern is similar to the observed in Europe, except of the route of transmission, where in Europe occured concomitantly, by parenteral route in drug users. Analysis of spatial distribution identified overlapping new areas of occurrence of HIV / AIDS and LV potentially signaling to increased risk of this new clinical entity as described above. Therefore, epidemiological surveillance for co-infection HIV / Leishmania should be adopted in all areas of risk of VL. At the same time, it is necessary to evaluate drug resistance currently used in the treatment of VL, as well as parenteral transmission of L infantum/ chagasi in areas where drug dependence is a risk factor for HIV acquisition / Leishmaniose visceral (LV) vem sofrendo modifica??es do ponto de vista cl?nico e epidemiol?gico mundialmente. Urbaniza??o foi descrita em diferentes regi?es do Brasil e do mundo, como tamb?m no estado do Rio Grande do Norte, influenciando sobremaneira no comportamento cl?nico da doen?a. Uma nova entidade cl?nica denominada co-infec??o HIV/leishmania vem sendo descrita, como conseq??ncia da sobreposi??o de ?reas de ocorr?ncia de LV e HIV/AIDS, em diferentes pa?ses incluindo o Brasil. O objetivo deste estudo foi definir o processo de periurbaniza??o da LV e descrever s?rie de casos da co-infec??o HIV/Leishmania no Rio Grande do Norte. Mudan?a no padr?o demogr?fico da LV no RN foi detectada, sendo observado aumento no n?mero de indiv?duos na idade adulta, do sexo masculino. An?lise da distribui??o espacial demonstrou que nos ?ltimos 20 anos LV tende a instalar-se em munic?pios de maior porte e, portanto, mais urbanizados do RN, sendo as regi?es leste e oeste as de maior risco para a doen?a. A primeira regi?o inclui Natal, capital do estado, onde o processo de periurbaniza??o iniciou-se, em 1990 e, a outra, inclui a cidade de Mossor?, segunda maior do estado, onde a periurbaniza??o iniciou-se nos ?ltimos 5 anos. Tamb?m em 1990 registra-se a emerg?ncia da co-infec??o HIV/ Leishmania no estado. Estudo tipo caso-controle revelou que a nova entidade cl?nica acomete indiv?duos adultos do sexo masculino, que adquirem HIV por via sexual; 40% destes com hist?ria de infec??o pr?via por leishmania. Reca?das e ?bito por LV ? maior em pacientes HIV positivos comparados com pacientes HIV negativos, pareados por sexo e idade. Esse padr?o ? bastante semelhante ao europeu, exceto, pela via de transmiss?o, que ocorre l? de modo concomitante, por via parenteral, em usu?rios de drogas il?citas. Adicionalmente, a an?lise de distribui??o espacial identificou sobreposi??o de ?reas de ocorr?ncia de HIV/AIDS e LV no RN apontando para risco aumentado da nova entidade cl?nica descrita acima. Portanto, vigil?ncia epidemiol?gica para co-infec??o HIV/Leishmania deve ser adotada em todas as ?reas de risco. Ao mesmo tempo, faz-se necess?rio avaliar resist?ncia ?s drogas utilizadas atualmente, no tratamento da LV, bem como, transmiss?o parenteral de L infantum/chagasi, nas ?reas onde a depend?ncia de droga ? fator de risco para aquisi??o de HIV

Resumo:A leishmaniose visceral é uma importante doença parasitária com distribuição mundial e que afeta homens e animais. Existem relatos de envolvimento encefálico durante a infecção, mas sua patogenia ainda não foi completamente elucidada. Com o presente estudo, objetivamos a avaliação de quimiocinas relacionadas com a resposta inflamatória no encéfalo e marcadores da integridade da barreira hematoencefálica em cães naturalmente infectados. Também foi estabelecido um modelo experimental murino que permite a avaliação da dinâmica da infecção, bem como localização do parasita e resposta inflamatória in vivo. Cães naturalmente infectados apresentaram um perfil específico de quimiocinas no encéfalo, altamente quimioatrativo para linfócitos T, além de evidente perda da integridade da barreira hematoencefálica, com elevado quociente de albumina e altas concentrações de anticorpos anti-Leishmania no líquido cefalorraquidiano. Utilizando inovadoras técnicas moleculares e de imagiologia in vivo, foi possível determinar a presença do parasita no encéfalo de camundongos Balb/c experimentalmente infectados, bem como sua localização intra-craniana. A inflamação no encéfalo, avaliada nos primeiros quatro meses pós-infecção, apresentou duas fases distintas, uma fase aguda nos primeiros quatorze dias, e uma fase de reinflamação após três meses de infecção. Conjuntamente, os dados desse estudo permitiram confirmar o envolvimento encefálico durante a leishmaniose visceral, e reforçam o fato de que o comprometimento encefálico tem sido negligenciado durante a leishmaniose visceral / Abstract:Visceral leishmaniasis is an important parasitic disease, with worldwide distributions that affects humans and animals. There are reports of brain involvement during the infection; however, its pathogenesis has not been completely elucidated. Therefore, with this study, we aimed the evaluation of the inflammatory response in the brain and the integrity of the blood-brain barrier in naturally infected dogs, and the establishment of an experimental mice model that could allow the evaluation of the infection dynamics, as well as the localization of the parasite and the inflammatory response in vivo. Naturally infected dogs presented a specific chemokine profile in the brain, highly attractive to T-lymphocytes, besides the evident blood-brain barrier disruption, with increased albumin quota and elevated concentrations of anti-Leishmania antibodies in the cerebrospinal fluid. Using molecular techniques and state-of-the-art in vivo imaging tools, we could determine the presence of parasites in the brain of experimentally infected Balb/c mice, as well as its intracranial localization. Brain inflammation, evaluated during four months post-infection, presented two distinct phases, one acute phase in the first fourteen days, and one phase of re-inflammation after three months of infection. Altogether, the data from this study allow us to confirm that the brain is affected during visceral leishmaniasis, and reinforce the fact that the brain involvement has been neglected during visceral leishmaniasis / Orientador:Gisele Fabrino Machado / Banca:Karen Regina Lemos / Banca:Valéria Marçal Felix de Lima / Banca:Cáris Maroni Nunes / Banca:Antonio Carlos Alessi / Doutor

Orientador: Gisele Fabrino Machado / Banca: Mary Marcondes / Banca: Rosemeri de Oliveira Vasconcelos / Resumo: A Leishmaniose visceral é uma enfermidade que possui uma grande variabilidade de manifestações clínicas, em humanos como em cães. Cães cronicamente infectados podem desenvolver desordens neurológicas, contudo, há poucos relatos que caracterizam as lesões e elucidam a patogenia da leishmaniose cerebral canina. Considerando a imunossupressão associada à leishmaniose visceral e que os patógenos oportunistas Toxoplasma gondii e Neospora caninum podem colaborar para a ocorrência de lesões no sistema nervoso central de cães naturalmente infectados por Leishmania chagasi, as populações de linfócitos B (CD79+) e T (CD3+) foram avaliadas no tecido nervoso de cães portadores de leishmaniose visceral e que possuem soropositividade para T. gondii e N. caninum. Lesões inflamatórias, caracterizadas por acúmulos de células mononucleares compostos principalmente por linfócitos T CD3+ predominaram em diversas regiões encefálicas dos cães infectados (P = 0,0012). Linfócitos B CD79+ foram detectados em pequena intensidade, não havendo diferença entre os grupos (P = 0,3604). Os resultados obtidos sugerem que a co-presença de leishmaniose visceral, toxoplasmose e neosporose é importante para o agravamento das lesões encefálicas, e que a imunossupressão gerada pela infecção por Leishmania não somente favorece a infecção por outros patógenos, mas colabora com esses, ocasionando lesões mais severas no tecido nervoso / Abstract: Visceral leishmaniasis is a disease with great variability regarding the clinical manifestations, in humans as in dogs. Chronically infected dogs may develop neurological disorders, however, there are few reports that characterise the lesions and make clear the pathogenesis of the canine cerebral leishmaniasis. Considering the immunossupression associated to visceral leishmaniasis and that the opportunist pathogens Toxoplasma gondii and Neospora caninum may collaborate to the occurrence of lesions in the central nervous system of dogs naturally infected by Leishmania chagasi, we evaluated the population of B (CD79+) and T (CD3+ ) lymphocytes in the nervous tissue of dogs with visceral leishmaniasis and with seropositivity to T. gondii and to N. caninum. Inflammatory lesions, characterised by mononuclear cellsaccumulation, composed mainly by CD3+ T lymphocytes predominated in several encephalic regions of the dogs from the infected groups (P=0.0012). CD79+ B lymphocytes were detected in very small intensity and presented no difference among groups (P=0.3604). The results presented herein suggest that the co-presence of visceral leishmaniasis, toxoplasmosis and neosporosis is important for the worsening of the encephalic lesions, and that the immunossupression caused by Leishmania infection not only propitiates the infection by other pathogens, but collaborate with them, causing more severe lesions in the brain / Mestre

ROCHA, MG. Mediadores inflamatórios na dor pélvica crônica Identificação de possíveis marcadores séricos da doença. Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, 2010. Introdução: Dor pélvica crônica é uma doença de elevada prevalência e fisiopatologia complexa. Os métodos diagnósticos muitas vezes são insuficientes e, em decorrência, o tratamento e seguimento das mulheres é difícil. Inúmeras doenças que se apresentam com dor crônica tem um perfil inflamatório, que ainda não foi investigado para o tema em questão. Objetivos: Quantificar os níveis de óxido nítrico (NO) e das metaloproteinases 2 (MMP-2) e 9 (MMP-9) no plasma de mulheres com dor pélvica crônica. Pacientes e métodos: Foram incluídas 64 mulheres, subdivididas em 02 grupos: dor pélvica crônica e grupo controle, com 37 pacientes no primeiro grupo e 27 pacientes no segundo grupo. As pacientes do grupo de estudo eram seguidas no Ambulatório de Dor Pélvica e Endoscopia e as pacientes do grupo controle eram seguidas no Ambulatório de Anticoncepção do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto USP. Foi realizada a mensuração clínica da dor através de uma escala unidimensional (VAS) e uma escala multidimensional (McGill). Também foram preenchidas as escalas de ansiedade e depressão (HAD). Indivíduos com qualquer evidência de processos inflamatórios, hipertensão, tabagismo ou uso de contraceptivos hormonais foram excluídos. Indivíduos tomando medicação para a dor, como analgésicos ou antiinflamatórios foram solicitados a pará-los 72 horas antes de participar do estudo. Foi coletada uma amostra sanguínea de 10 ml, no ato da consulta. Esse material foi armazenado em frasco próprio com anti-coagulante, processado imediatamente no local para separação do plasma e armazenado em freezer, a -70C para mensuração subseqüente. As concentrações de espécies relacionadas ao NO (nitrato) em líquidos foram medidas, sempre em triplicata, pelo método da quimioluminescência, que é um dos métodos mais simples, sensíveis e precisos disponíveis para medir NO. Foi utilizado um analisador de NO (Sievers Model 280 NO Analyzer - Boulder, CO, EUA), o qual permite medir NO em quantidades tão pequenas quanto 1 pmol. A atividade das MMP-2 e MMP-9 no plasma serão determinadas pelo método da zimografia, que consiste em uma eletroforese das amostras em um sistema SDS/PAGE que inclui o substrato da enzima (gelatina) no gel de separação, de modo a permitir a evidenciação e quantificação da atividade da enzima. Resultados: Os níveis plasmáticos de NO foram maiores nas pacientes com DPC quando comparadas às pacientes do grupo controle (16.8 ± 7.9 versus 12.2 ± 2.4, respectivamente (P = 0.0016). Especificamente, os níveis plasmáticos de NO foram maiores nas pacientes com DPC de origem visceral quando comparadas às pacientes com dor exclusivamente somática ou aos controles saudáveis (19.2 ± 8.9 versus 12.4 ± 1.8 versus 12.2 ± 2.4, respectivamente) (P=0.0001). Não observamos uma correlação entre os níveis plasmáticos de NO e a duração dos sintomas (em meses) (Spearman r = 0.04, 95%CI:-0.34 to 0.40, P = 0.84) ou com a intensidade dos sintomas dolorosos: EAV (Spearman r =:-0.18, 95%CI:-0.52 to 0.20, P=0.34), ou McGill (Spearman r = -0.06, 95%CI:-0.41 to 0.30, P =0.72). Com relação às MMP´s, não houve diferença estatística entre os dois grupos. Conclusões: Os níveis plasmáticos de NO encontram-se elevados em mulheres com DPC, especialmente naquelas com dor de origem visceral. Este fato pode ser considerado uma possibilidade no seguimento de pacientes com DPC, visto que pode ser usado como um marcador sérico para a doença. Já a dosagem das MMP-s não se mostrou útil como marcador plasmático para mulheres com DPC. / Background: Chronic pelvic pain is a disease of high prevalence and a complex pathophysiology. The diagnostic methods are often inadequate and, consequently, treatment and follow-up of women is quite difficult. Several diseases that present with chronic pain has an inflammatory profile, which has not yet been investigated for the topic. Aim: to quantify levels of nitric oxide (NO) and metalloproteinases 2 (MMP-2) and 9 (MMP-9) in plasma of women with chronic pelvic pain. Methods: 64 women were included in the sudy and divided into 02 groups: chronic pelvic pain and control group with 37 patients in the first group and 27 patients in the second group. Patients in the study group were followed at the Endoscopy and Pelvic Pain Unit and the control group patients were followed in the Contraception Unit of the Hospital of the Medical School of Ribeirão Preto University of São Paulo. We performed the measurement of clinical pain by a unidimensional scale (VAS) and a multidimensional scale (McGill). Anxiety and depression scales were also filled. Individuals with any evidence of inflammation, hypertension, smoking or use of hormonal contraceptives were excluded. Individuals taking medication for pain, such as painkillers or antiinflammatory drugs were asked to stop them 72 hours before entering the study. A blood sample was collected from 10 ml during the appointment. This material was stored in bottle itself with anti-coagulant (EDTA and / or heparin), processed immediately on site for plasma separation and stored in a -70 ºC freezer. The concentrations of species related to NO were measured in liquid, always in triplicate by the method of chemiluminescence, which is one of the most simple, sensitive and accurate available to measure NO. We used a NO analyzer (Sievers Model 280 NO Analyzer - Boulder, CO, USA), which allows the measurement of NO in quantities as small as 1 pmol. The activity of MMP-2 and MMP-9 in plasma was determined by the zymography method, which consists of an electrophoresis of the samples in an SDS / PAGE system, which includes the enzyme substrate (gelatin) in the gel separation, allowing the disclosure and quantification of enzyme activity. Results: Plasma NO levels were higher in CPP women than in controls (16.8 ± 7.9 versus 12.2 ± 2.4, respectively) (P=0.0016). Furthermore, plasma nitrate levels were higher in CPP women with evidence of pain of visceral origin than in CPP women with evidence of an exclusive somatic component or controls (19.2 ± 8.9 versus 12.4 ± 1.8 versus 12.2 ± 2.4, respectively) (P=0.0001). No correlation was detected between NO levels and duration of symptoms or intensity of pain. Regarding the MMP\'s, there was no statistical difference between the two groups. Conclusion: Plasma levels of NO are elevated in women with CPP, especially those with visceral pain. This fact can be considered an option in treating patients with CPP as it can be used as a serum marker for the disease. On the other hand, MMP´s did not turn out to be a good serum marker for women with CPP.

Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) which can be defined as chronic, relapsing visceral pain with bloating associated with change in bowel habit. It affects up to 10-15% of the adult population in the UK and is more common in females. The cost of IBS in terms of health care utilisation is substantial, exceeding £45.6 million per year in the UK alone, yet its pathophysiology is incompletely understood. Visceral pain is the main and most difficult symptom to manage in IBS and many IBS female sufferers compare it to labour pain in its severity. Modulating visceral pain in healthy volunteers and IBS patients is therefore an important research area. Non-invasive magnetic stimulation may play a crucial role in this respect. Aim:The aim of this study is to ascertain whether non-invasive repetitive magnetic stimulation applied to the motor cortex and/or lumbosacrum can modulate gastrointestinal pain originating from the anorectum. Methods:Participants: 16 healthy volunteers and 10 IBS patients aged 18 and above were included in the study.Questionnaires: Healthy volunteers and IBS patients were asked to complete anxiety and depression questionnaire and IBS patients were requested to fill in an IBS severity questionnaire.Motor measurements in healthy subjects: Single-pulse lumbosacral magnetic stimulation (LSMS) was applied to the lumbosacral area for the anal sphincter where the largest motor evoked potential (MEP) amplitude response was detected. Single-pulse transcranial magnetic stimulation (TMS) was then performed at the pre-determined resting motor thresholds (RMT) for the anal sphincter and the hand.Sensory measurements in healthy subjects and IBS patients: Electrical stimulation was used to assess the changes in sensory and pain thresholds in the anorectal area. The subjects were asked to score the pain intensity using five-point categorical rating scales. In addition they were asked to describe the pain experienced using a shortened form of the McGill Pain Questionnaire. Intervention: Healthy volunteers received 6 paradigms of magnetic stimulation in a randomised order i.e. 3 repetitive LSMSs (1 Hz, 10 Hz and sham) and 3 repetitive TMSs (1 Hz, 10 Hz and sham) to investigate their modulatory effects on visceral sensitivity and to determine which of these interventions is most effective. The most effective active interventions (1 Hz rLSMS and 10 Hz rTMS) together with one sham were then trialled in a randomised fashion on IBS patients.Post intervention: Motor excitabilities were repeated at 30 min after each intervention. The assessment of sensory and pain thresholds at anal sphincter and rectum were done immediately, 30 and 60 min after each intervention. Results:Application of 1 Hz rLSMS led to alterations of anal sphincter motor excitabilities and resulted in a significant increase in the amplitude of lumbosacal-anal motor evoked potentials (MEPs) in healthy volunteers recorded at 30 min post intervention. In healthy volunteers, 1 Hz rLSMS and 10 Hz rTMS caused a significant increase in the rectal pain thresholds experienced immediately, 30 and 60 min after each intervention. 10 Hz rLSMS and 1 Hz rTMS only led to a significant rise in rectal pain thresholds immediately after their application. Furthermore, there was a significant increase in the rectal pain thresholds immediately, 30 and 60 min following 1 Hz rLSMS and 10 Hz rTMS in IBS patients. Conclusion:The application of magnetic stimulation to the cortical and lumbosacral areas to modulate visceral pain is a new concept, which reduced rectal sensitivity to painful stimuli and offers a much needed new approach in the management of abdominal pain in patients with IBS.

Background: Irritable bowel syndrome (IBS) is an extremely common condition affecting approximately 10-15% of the population. Lower abdominal pain is a common feature and, if the patient also has gynaecological symptoms such as heavy periods, they may be referred to a gynaecologist especially when the bowel symptoms are relatively mild. In this setting a laparoscopy is often undertaken and endometriosis commonly identified as this condition affects up to 10% of women. Consequently pain is frequently attributed to the endometriosis even when it is relatively mild. However it is a common observation amongst gynaecologists that women with mild endometriosis often have severe symptoms which do not seem to respond well to treatment. This raises the possibility that their pain may not actually be due to endometriosis or is being amplified by the visceral hypersensitivity which is a characteristic feature of irritable bowel syndrome.Methods: 20 patients with minimal-mild endometriosis, 20 with moderate-severe endometriosis, 20 healthy volunteers (HV) who have had laparoscopy for sterilisation, 20 IBS patients and 20 patients with pain who were found to have a normal pelvis (on laparoscopy) were studied. Gastrointestinal, gynaecological, and noncolonic symptoms were recorded as well as demography, quality of life and psychological status. Visceral sensitivity was assessed in all patients and abdominal distension was studied in a sub group of 26 endometriosis patients and 20 IBS patients.Results: 20 (100%) of IBS patients, 13 (65%) of minimal-mild endometriosis patients, 11 (55%) of moderate-severe endometriosis patients, 17 (85%) of laparoscopic negative pain patients and no healthy volunteers fulfilled ROME III criteria for IBS. Patients with endometriosis and IBS had similar levels of visceral sensitivity which were significantly lower than that observed in controls (p=0·002, p<0·001).In particular, both minimal-mild and moderate-severe endometriosis patients had significantly lower (mean-95% CI) pain thresholds in mmHg 28.1(24.5, 31.6) and 28.8(24.9, 32.6) respectively compared with controls 39·5 (36·0, 43·0) p=0.001and p=0.002. However, with few exceptions, there were no distinguishing features between patients in terms of demography, symptomatology and distension.Conclusion: Clinically, it is very difficult to distinguish between endometriosis and IBS. However, visceral hypersensitivity appears to be a major component of endometriosis and may explain the problem of excessive pain especially in patients with mild disease offering a potential new target for treatment

Purpose: This paper attempts to develop production functions (PF) between aerobic exercise inputs and long-run health outputs. Future studies could use such PF for estimating the benefits and costs (broadly defined) of different exercise programs to help develop optimal (utility maximizing) ones. Methods: To develop the PF, the paper reviewed the biomedical literature for the major dose-response relations between health, physical fitness, and exercise. Where relevant, the paper converted the dose-response relationships from relative risks to absolute probabilities and standardized terminology and units of measures. Results: The paper develops a clear set of biological PF that illustrate, quantitatively, how increases in peak cardiorespiratory (CR) fitness as measured by a short stress test reduce the probability of all-cause mortality; how increasing intensities of short (approximately 30 min, three to five times a week) exercise sessions increase peak CR fitness or retard its age-related decline; and how consistent exercise reduces the risk of myocardial infarctions (MI). Conclusions: The exercise-long-run health PF developed in this paper should provide a useful framework for other studies to estimate the broadly defined costs and benefits of different exercise programs and to help develop optimal ones.

Image-based quantifications of visceral adipose tissue (VAT) volumes from segmented VAT areas are increasingly considered for risk assessment in obese patients. The goal of this study was to determine the power of partial VAT areas to predict total VAT volume in morbidly obese patients (BMI > 40 kg/m2) as a function of gender, age and anatomical landmarks. 130 morbidly obese patients (mean BMI 46.5 kg/m2; 94 females) underwent IRB-approved MRI. Total VAT volumes were predicted from segmented VAT areas (of single or five adjacent slices) at common axial landmark levels and compared with the measured ones (VVAT-T, about 40 slices between diaphragm and pelvic floor). Standard deviations σ1 and σ5 of the respective VAT volume differences served as measures of agreement. Mean VVAT-T was 4.9 L for females and 8.1 L for males. Best predictions were found at intervertebral spaces L3-L4 for females (σ5 = 688 ml, σ1 = 832 ml) and L1-L2 for males (σ5 = 846 ml, σ1 = 992 ml), irrespective of age. In conclusion, VAT volumes in morbidly obese patients can be reliably predicted by multiplying the segmented VAT area at a gender-specific lumbar reference level with a fixed scaling factor and effective slice thickness.

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We have recently demonstrated that C57BL/6NTac and C57BL/6JRj substrains are significantly different in their response to high-fat diet-induced obesity (DIO). The C57BL/6JRj substrain seems to be protected from DIO and genetic differences between C57BL/6J and C57BL/6N substrains at 11 single nucleotide polymorphism (SNP) loci have been identified. To define genetic variants as well as differences in parameters of glucose homeostasis and insulin sensitivity between C57BL/6NTac and C57BL/6JRj substrains that may explain the different response to DIO, we analyzed 208 first backcross (BC1) hybrids of C57BL/6NTac and C57BL/6JRj [(C57BL/6NTac × C57BL/6JRj)F1 × C57BL/6NTac] mice. Body weight, epigonadal and subcutaneous fat mass, circulating leptin, as well as parameters of glucose metabolism were measured after 10 wk of high-fat diet (HFD). Genetic profiling of BC1 hybrids were performed using TaqMan SNP genotyping assays. Furthermore, to assess whether SNP polymorphisms could affect mRNA level, we carried out gene expression analysis in murine liver samples. Human subcutaneous adipose tissue was used to verify murine data of SNAP29. We identified four sex-specific variants that are associated with the extent of HFD-induced weight gain and fat depot mass. BC1 hybrids carrying the combination of risk or beneficial alleles exhibit the phenotypical extremes of the parental strains. Murine and human SC expression analysis revealed Snap29 as strongest candidate. Our data indicate an important role of these loci in responsiveness to HFD-induced obesity and suggest genes of the synaptic vesicle release system such as Snap29 being involved in the regulation of high-fat DIO.