TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous polymorphism in TM6SF2 (rs58542926 c.449 C>T, p.Glu167Lys) was recently associated with increased hepatic triglyceride content, but whether this variant promotes clinically relevant hepatic fibrosis is unknown. Here we confirm that TM6SF2 minor allele carriage is associated with NAFLD and is causally related to a previously reported chromosome 19 GWAS signal that was ascribed to the gene NCAN. Furthermore, using two histologically characterized cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n=1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD.

Estimating the prevalence of comorbid conditions and their effect on health care costs in patients with diabetes mellitus in Switzerland.

BACKGROUND Estimating the prevalence of comorbidities and their associated costs in patients with diabetes is fundamental to optimizing health care management. This study assesses the prevalence and health care costs of comorbid conditions among patients with diabetes compared with patients without diabetes. Distinguishing potentially diabetes- and nondiabetes-related comorbidities in patients with diabetes, we also determined the most frequent chronic conditions and estimated their effect on costs across different health care settings in Switzerland. METHODS Using health care claims data from 2011, we calculated the prevalence and average health care costs of comorbidities among patients with and without diabetes in inpatient and outpatient settings. Patients with diabetes and comorbid conditions were identified using pharmacy-based cost groups. Generalized linear models with negative binomial distribution were used to analyze the effect of comorbidities on health care costs. RESULTS A total of 932,612 persons, including 50,751 patients with diabetes, were enrolled. The most frequent potentially diabetes- and nondiabetes-related comorbidities in patients older than 64 years were cardiovascular diseases (91%), rheumatologic conditions (55%), and hyperlipidemia (53%). The mean total health care costs for diabetes patients varied substantially by comorbidity status (US$3,203-$14,223). Patients with diabetes and more than two comorbidities incurred US$10,584 higher total costs than patients without comorbidity. Costs were significantly higher in patients with diabetes and comorbid cardiovascular disease (US$4,788), hyperlipidemia (US$2,163), hyperacidity disorders (US$8,753), and pain (US$8,324) compared with in those without the given disease. CONCLUSION Comorbidities in patients with diabetes are highly prevalent and have substantial consequences for medical expenditures. Interestingly, hyperacidity disorders and pain were the most costly conditions. Our findings highlight the importance of developing strategies that meet the needs of patients with diabetes and comorbidities. Integrated diabetes care such as used in the Chronic Care Model may represent a useful strategy.

[Klinik und Diagnose von Hypogonadismus und Andropause]

Diagnosis and therapy of male hypogonadism is still a challenge because of the unspecific clinical signs and symptoms. The clinical presentation of a androgen deficiency is age-related. In the adult men, one can often observe fatigue, decrease in physical capacity, loss of libido and erectile dysfunction. At the physical examination, genitalia have always to be assessed in search of a testes/penis atrophy. Two fasting measurements of total testosterone concentrations by a reliable assay are needed to confirm the diagnosis. By assessing gonadotropines the origin of hypogonadism can be determined (central/secondary or peripheral/primary). Exogenous administration of androgens should be considered in young, sportive, healthy and muscular males. Patients with metabolic syndrome should only be screened for hypogonadism in the presence of suggestive symptoms. Prostate disease, hematocrit higher than 50 %, uncontrolled heart failure and severe obstructive sleep apnea are contraindications of a testosterone replacement therapy. Patients with metabolic-syndrome-associated low testosterone levels should firstly benefit from a lifestyle intervention that can normalize clinical and biochemical hypogonadism. So far, there is no clear evidence for a possible benefit of testosterone therapy in patients with the metabolic syndrome. Similarly, in patients with PADAM (partial androgen deficiency of the aging male) testosterone therapy is not established or recommended.

Synergistic action of image-guided radiotherapy and androgen deprivation therapy.

The combined use of androgen deprivation therapy (ADT) and image-guided radiotherapy (IGRT) can improve overall survival in aggressive, localized prostate cancer. However, owing to the adverse effects of prolonged ADT, it is imperative to identify the patients who would benefit from this combined-modality therapy relative to the use of IGRT alone. Opportunities exist for more personalized approaches in treating aggressive, locally advanced prostate cancer. Biomarkers--such as disseminated tumour cells, circulating tumour cells, genomic signatures and molecular imaging techniques--could identify the patients who are at greatest risk for systemic metastases and who would benefit from the addition of systemic ADT. By contrast, when biomarkers of systemic disease are not present, treatment could proceed using local IGRT alone. The choice of drug, treatment duration and timing of ADT relative to IGRT could be predicated on these personalized approaches to prostate cancer medicine. These novel treatment intensification and reduction strategies could result in improved prostate-cancer-specific survival and overall survival, without incurring the added expense of metabolic syndrome and other adverse effects of ADT in all patients.

Circulating oxidized LDL is associated with the occurrence of echolucent plaques in the carotid artery in 61-year-old men.

OBJECTIVE The aim of this study was to elucidate the relationship between the echogenicity of carotid artery plaques and the following risk factors: circulating oxLDL, hsCRP, the metabolic syndrome (MetS), and several of the traditional cardiovascular (CV) risk factors. MATERIAL AND METHODS A cross-sectional population-based study of 513 sixty-one-year-old men. The levels of circulating oxLDL were determined in plasma samples by sandwich ELISA utilizing a specific murine monoclonal antibody (mAb-4E6). High-sensitivity CRP was measured in plasma by ELISA. Plaque occurrence, size and echogenicity were evaluated from B-mode ultrasound registrations in the carotid arteries. Plaque echogenicity was assessed based on a four-graded classification scale. RESULTS A higher frequency of echolucent carotid plaques was observed with increasing levels of oxLDL and systolic blood pressure (p = 0.008 and p = 0.041, respectively). Subjects with the MetS had a significantly higher frequency of echogenic plaques than subjects without the MetS (p = 0.009). In a multiple logistic regression analysis, oxLDL turned out to be independently associated with echolucent carotid plaques. CONCLUSIONS The occurrence of echolucent carotid plaques was associated with oxLDL and systolic blood pressure, and oxLDL was associated with echolucent carotid plaques independently of systolic blood pressure.

Circulating oxidized low-density lipoprotein is associated with echolucent plaques in the femoral artery independently of hsCRP in 61-year-old men.

OBJECTIVES The aim of the study was to test the hypothesis that circulating markers of inflammation (high-sensitive C-reactive protein, hsCRP) and oxidative modification of lipids (oxidized low-density lipoprotein, oxLDL) were associated with the occurrence of echolucent rather than echogenic femoral artery plaques in a cross-sectional population based cohort of 513, 61-year-old men. BACKGROUND The relationships between circulating oxLDL, hsCRP and the occurrence of echolucent plaques in the femoral artery have not previously been investigated. METHODS The levels of circulating oxLDL and hsCRP were determined in plasma by ELISA. Plaque occurrence, size and echogenicity were measured by B-mode ultrasound in the right femoral artery. Assessment of plaque echogenicity was based on the classification (grades 1-4) proposed by Gray-Weale et al. RESULTS A higher frequency of echolucent femoral plaques was observed in subjects with the metabolic syndrome and current smokers (p=0.01 and p<0.001, respectively) as well as with increasing levels of oxLDL and hsCRP (p=0.002 and p=0.005, respectively). In a multiple logistic regression analysis oxLDL and current smokers turned out to be independent associated with the presence of echolucent femoral artery plaques. CONCLUSIONS The results of the present study support our hypothesis that circulating oxLDL is a marker of an unstable echolucent plaque phenotype in the femoral artery in man.

European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa

Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100,000 person-years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade-relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered.

Thrombosis during pregnancy: Risks, prevention, and treatment for mother and fetus--harvesting the power of omic technology, biomarkers and in vitro or in vivo models to facilitate the treatment of thrombosis

Maternal thromboembolism and a spectrum of placenta-mediated complications including the pre-eclampsia syndromes, fetal growth restriction, fetal loss, and abruption manifest a shared etiopathogenesis and predisposing risk factors. Furthermore, these maternal and fetal complications are often linked to subsequent maternal health consequences that comprise the metabolic syndrome, namely, thromboembolism, chronic hypertension, and type II diabetes. Traditionally, several lines of evidence have linked vasoconstriction, excessive thrombosis and inflammation, and impaired trophoblast invasion at the uteroplacental interface as hallmark features of the placental complications. "Omic" technologies and biomarker development have been largely based upon advances in vascular biology, improved understanding of the molecular basis and biochemical pathways responsible for the clinically relevant diseases, and increasingly robust large cohort and/or registry based studies. Advances in understanding of innate and adaptive immunity appear to play an important role in several pregnancy complications. Strategies aimed at improving prediction of these pregnancy complications are often incorporating hemodynamic blood flow data using non-invasive imaging technologies of the utero-placental and maternal circulations early in pregnancy. Some evidence suggests that a multiple marker approach will yield the best performing prediction tools, which may then in turn offer the possibility of early intervention to prevent or ameliorate these pregnancy complications. Prediction of maternal cardiovascular and non-cardiovascular consequences following pregnancy represents an important area of future research, which may have significant public health consequences not only for cardiovascular disease, but also for a variety of other disorders, such as autoimmune and neurodegenerative diseases.

EMAS position statement: Testosterone replacement therapy in the aging male‏.

INTRODUCTION Late-onset hypogonadism (LOH) represents a common clinical entity in aging males, characterized by the presence of symptoms (most usually of a sexual nature, such as decreased libido, decreased spontaneous erections and erectile dysfunction) and signs, in combination with low serum testosterone concentrations. Whether testosterone replacement therapy (TRT) should be offered to those individuals is still under extensive debate. AIMS The aim of this position statement is to provide and critically appraise evidence on TRT in the aging male, focusing on pathophysiology and characteristics of LOH, indications for TRT, available therapeutic agents, monitoring and treatment-associated risks. MATERIALS AND METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS Diagnosis and treatment of LOH is justified, if a combination of symptoms of testosterone deficiency and low testosterone is present. Patients receiving TRT could profit with regard to obesity, metabolic syndrome, type 2 diabetes mellitus, sexual function and osteoporosis and should undergo scheduled testing for adverse events regularly. Potential adverse effects of TRT on cardiovascular disease, prostate cancer and sleep apnea are as yet unclear and remain to be investigated in large-scale prospective studies. Management of aging men with LOH should include individual evaluation of co-morbidities and careful risk versus benefit assessment.

Adiposity and the perilipin gene: The role of single locus and multilocus variation, obesity-related quantitative traits, and disease-related phenotypes in the Atherosclerosis Risk in Communities (ARIC) study

Obesity is a complex multifactorial disease and is a public health priority. Perilipin coats the surface of lipid droplets in adipocytes and is believed to stabilize these lipid bodies by protecting triglyceride from early lipolysis. This research project evaluated the association between genetic variation within the human perilipin (PLIN) gene and obesity-related quantitative traits and disease-related phenotypes in Non-Hispanic White (NHW) and African American (AA) participants from the Atherosclerosis Risk in Communities (ARIC) Study. ^ Multivariate linear regression, multivariate logistic regression, and Cox proportional hazards models evaluated the association between single gene variants (rs2304794, rs894160, rs8179071, and rs2304795) and multilocus variation (rs894160 and rs2304795) within the PLIN gene and both obesity-related quantitative traits (body weight, body mass index [BMI], waist girth, waist-to-hip ratio [WHR], estimated percent body fat, and plasma total triglycerides) and disease-related phenotypes (prevalent obesity, metabolic syndrome [MetS], prevalent coronary heart disease [CHD], and incident CHD). Single variant analyses were stratified by race and gender within race while multilocus analyses were stratified by race. ^ Single variant analyses revealed that rs2304794 and rs894160 were significantly related to plasma triglyceride levels in all NHWs and NHW women. Among AA women, variant rs8179071 was associated with triglyceride levels and rs2304794 was associated with risk-raising waist circumference (>0.8 in women). The multilocus effects of variants rs894160 and rs2304795 were significantly associated with body weight, waist girth, WHR, estimated percent body fat, class II obesity (BMI ≥ 35 kg/m2), class III obesity (BMI ≥ 35 kg/m2), and risk-raising WHR (>0.9 in men and >0.8 in women) in AAs. Variant rs2304795 was significantly related to prevalent MetS among AA males and prevalent CHD in NHW women; multilocus effects of the PLIN gene were associated with prevalent CHD among NHWs. Rs2304794 was associated with incident CHD in the absence of the MetS among AAs. These findings support the hypothesis that variation within the PLIN gene influences obesity-related traits and disease-related phenotypes. ^ Understanding these effects of the PLIN genotype on the development of obesity can potentially lead to tailored health promotion interventions that are more effective. ^

Caracterización y cuantificación de células progenitoras endoteliales de ratas espontáneamente hipertensas alimentadas con fructosa

Objetivo: Examinar cómo se ve afecta la participación de las células progenitoras endoteliales (CPE) por la resistencia a la insulina (IR) asociada a un modelo experimental de síndrome metabólico (SM), generado por la administración crónica de fructosa a ratas espontáneamente hipertensas. Material y métodos: Ratas WKY y SHR, macho, distribuidas en 4 grupos (n=8 c/u): WKY: controles; FFR: WKY recibiendo fructosa en agua de bebida al 10 % (v/v) durante 6 semanas; SHR; FFHR: SHR recibiendo fructosa en agua de bebida al 10 % (v/v) durante 6 semanas. Al finalizar el protocolo se determinó: presión arterial sistólica, variables bioquímicas, índice HOMA, cuantificación por citometría de flujo de los niveles de CPE en sangre periférica y en médula ósea, inmunofluorescencia en cultivo celular, para identificar los marcadores CD34 y VEGFR-2, recuento de colonias de CPE y actividad de NAD(P)H-oxidasa en tejido aórtico. Resultados: Se confirmó el modelo experimental en base a las variables metabólicas analizadas. Se observó una disminución en los niveles de CPE; en sangre periférica y médula ósea, la que se hace más importante en los grupos de animales tratados con fructosa. En estos también hay menor número de colonias de CPE desarrolladas en cultivo celular y presentan un aumento en los niveles de estrés oxidativo, estimado por la actividad de NAD(P)H oxidasa. Conclusión: el SM causado por la administración crónica de fructosa en FFHR ha demostrado generar una disminución en los niveles de CPE, así como en su capacidad funcional. Los mecanismos intracelulares que producen este fenómeno podrían estar desencadenados por el grado de IR que presenta este modelo experimental.

Adipocitoquinas y síndrome metabólico : rol de la vistafina en la patogenia de enfermedad cardiovascular

La enfermedad cardiovascular es la primera causa de morbi-mortalidad en los países industrializados. El síndrome metabólico, caracterizado por hipertensión, dislipidemia, obesidad e hiperglucemia, constituye el principal factor de riesgo para la enfermedad cardiovascular. El tejido adiposo visceral juega un papel fundamental en este proceso, dado que secreta una variedad de sustancias biológicamente activas denominadas adipoquinas o adipocitoquinas, tales como leptina, resistina, adiponectina, factor de necrosis tumoral alfa (TNFa), y visfatina entre otras. La visfatina es una citoquina descubierta recientemente y su rol en la enfermedad cardiovascular es controversial y aún no ha sido completamente dilucidado. Estudios realizados en humanos y en modelos experimentales en animales sugieren que la visfatina tendría un papel muy importante en las patologías asociadas a la enfermedad cardiovascular. Esta revisión intenta mostrar los últimos avances sobre el rol de la visfatina y las principales adipocitoquinas en las patologías cardiovasculares y el síndrome metabólico.

Risco cardiovascular e sua associação com variáveis demográficas, clínicas e psicossociais em pessoas vivendo com HIV/aids

Trata-se de um estudo analítico de corte transversal, que visa avaliar o risco cardiovascular de PVHA segundo o Escore de Framingham e identificar a associação entre o risco e as variáveis demográficas, comportamentais, psicossociais e clínicas de PVHA. O estudo foi aprovado na Secretaria Municipal de Saúde e no Comitê de Ética da Escola de Enfermagem de Ribeirão Preto, a coleta de dados foi realizada no período de outubro de 2014 a agosto de 2015 em cinco Serviços de Atendimento Especializado às PVHA utilizando questionário sociodemográfico, clínico e comportamental, avaliação da alimentação saudável, Inventário de Sintomas de Stress para Adultos de Lipp e avaliação do risco cardiovascular por meio do Escore de Framingham. A análise dos dados ocorreu através de estatística descritiva e teste de associação entre as variáveis, onde foi adotado nível de significância com valor de p<0,05. Identificou-se que 58,3% pertenciam ao sexo masculino, 69,1% apresentavam idade acima de 40 anos, com média de 44,4 anos, 40,6% referiram ser brancos e 40,0% pardos, e 70,9% eram heterossexuais. Observou-se que 64,0% eram sedentários, 35,4% tabagistas e 40,0% faziam uso de bebida alcóolica regularmente. Do mesmo modo, 73,7% consideraram sua alimentação saudável, no entanto, ao ser avaliado de acordo com o escore da alimentação saudável, 70,9% obtiveram score intermediário para alimentação. Com relação às variáveis psicossociais, foi identificado que 52,0% tinham menos de oito anos de estudo, e 80,6% referiram receber até três salários mínimos por mês. Quanto aos sintomas de estresse, foi visto que 29,1% e 22,3% estavam nas fases de resistência e exaustão, respectivamente. Além disso, identificou-se que 15,4% da amostra tinha diagnóstico médico para depressão e que 71,4% não realizavam atividades de lazer regularmente. Com relação às variáveis clínicas gerais, 57,7% referiram antecedentes familiares para HAS, 40,6% para DM, 21,7% para IAM e 27,4% para AVE. Quanto aos antecedentes pessoais, foi visto que 15,4% eram hipertensos, 8,0% eram diabéticos e 8,0% tinham dislipidemia. Desta mesma amostra, 45,2% apresentavam IMC maior que 25,0 kg/m² e 41,7% estavam em síndrome metabólica. Com relação às variáveis clínicas relacionadas ao HIV, observou-se que 42,2% e 32,0% possuíam o diagnóstico de soropositividade e fazem uso de TARV há mais de dez anos, respectivamente. A contagem de células TCD4+ e carga viral mostrou que 82,8% dos participantes apresentaram contagem maior que 350 cels/mm³, e 80,6% tinham carga viral indetectável. Foi identificado que 25,8% dos sujeitos apresentam risco cardiovascular de médio a alto, segundo o Escore de Framingham. Apenas as variáveis sociodemográficas sexo (p=0,006), idade (p<0,001) e estado civil (p=0,003) apresentaram associação com o risco cardiovascular calculado pelo Escore de Framingham. Nas variáveis comportamentais, as fases de estresse (p=0,039) tiveram associação com o risco cardiovascular, e com relação às variáveis clínicas, antecedentes familiares para DM (p=0,035), HAS, DM e SM (p<0,001) e DLP (p=0,030) apresentaram significância estatística. Nas variáveis clínicas relacionadas ao HIV, o tempo de diagnóstico (p=0,005) e o tempo de TARV (p=0,038) também apresentaram associação. Conclui-se que 25,8% de PVHA no município de Ribeirão Preto apresentam risco cardiovascular de moderado a alto, medido pelo Escore de Framingham

Variáveis associadas a não adesão à terapia medicamentosa em idosos hipertensos e com comorbidades de uma unidade pública de saúde de Ribeirão Preto-SP

A adesão ao tratamento ocorre quando o conselho médico ou de saúde coincide com o comportamento do indivíduo, ao uso de medicamentos, cumprimento da dieta e mudanças no estilo de vida, não sendo, portanto, um ato não passivo do paciente. Em pacientes com hipertensão arterial sistêmica a adesão ao tratamento pode ser definida como o grau de cumprimento das medidas terapêuticas indicadas, sejam elas medicamentosas ou não, com o objetivo de manter a pressão arterial em níveis pressóricos normais. A não adesão em pacientes com doenças crônicas em tratamento a longo prazo em países desenvolvidos é em média de 50%, revelando a importância de serem avaliados os motivos que levam a esse comportamento. O estudo teve como objetivo avaliar a não adesão em idosos hipertensos de uma unidade pública de saúde de Ribeirão Preto - SP. Trata-se de um estudo de corte transversal, desenvolvido com uma amostra de 196 pessoas. A coleta de dados ocorreu entre agosto de 2014 até junho de 2015, após aprovação do Comitê de Ética em Pesquisa. Para essa etapa foram utilizados os instrumentos Brief Medication Questionnaire, Medical Outcomes Studies 36-item Short Form Survey, Escore de Risco Global e Escore de Risco pelo Tempo de Vida. Após a coleta dos dados, as entrevistas foram codificadas, os dados foram tabulados e foi realizada a análise estatística descritiva e de correlação. Como resultado, constatou-se que houve predomínio de mulheres, com idade média de 69,4 anos, casados/união estável, não moravam sozinhos, com 1,85 pessoas na casa em média, de cor branca, com ensino fundamental incompleto, renda de até dois salários mínimos e aposentados/pensionistas, atendidos pelo SUS. Apresentaram hábitos de vida razoáveis, sem predomínio de consumo de bebidas alcoólicas, tabagismo, uso excessivo de sal e sedentarismo. A mais frequente comorbidade associada à HAS foi a dislipidemia. Foi observado elevado predomínio de fatores de risco cardiovasculares como obesidade abdominal, obesidade geral, comorbidades, razão de lipídeos e fatores agravantes como proteína c reativa ultrassensível, microalbuminúria e síndrome metabólica. A maioria da amostra foi classificada como sendo portador de risco cardiovascular alto após estratificação do risco. A percepção da qualidade de vida relacionada à saúde foi considerada baixa na maioria principalmente devido a limitações emocionais. A não adesão esteve presente em quase metade dos idosos, relacionada principalmente à complexidade da farmacoterapia e dificuldade em lembrar sobre o uso de seus medicamentos. Não foi observada correlação entre a não adesão e as variáveis estudadas. Conclui-se que o comportamento de não adesão observado não esteve relacionada às variáveis estudadas nessa amostra e que são necessárias intervenções urgentes para reduzir o risco cardiovascular e prevenir doenças cardiovasculares e mortalidade, bem como melhora da percepção da qualidade de vida relacionada à saúde.

PGC-1 alfa como regulador inflamatório na esteato-hepatite não-alcoólica

A doença hepática gordurosa não-alcoólica (NAFLD, do inglês) é a manifestação clínica hepática da síndrome metabólica, cuja incidência aumenta consideravelmente em todo o mundo. A NAFLD pode progredir para um estado de esteatohepatite não-alcoólica (NASH, do inglês), caracterizado por inflamação hepatocelular, com ou sem fibrose. Dados na literatura mostram que o coativador-1 alfa do receptor ativado por proliferadores de peroxissoma gama (PGC-1alfa), além de estar envolvido em diversos processos metabólicos, representa uma estratégia terapêutica promissora na modulação da inflamação. Neste projeto investigamos as alterações inflamatórias no fígado induzida por dieta hiperlipídica e o papel do PGC-1alfa nesse processo. Camundongos C57black/6 receberam dieta hiperlipídica contendo 30% de gordura por 10 semanas. O peso dos animais foi avaliado semanalmente. Após a eutanásia, o tecido adiposo intra-abdominal (retroperitoneal e periepididimal) foi coletado e pesado. Analisamos o perfil glicêmico e lipídico sérico e expressão de genes envolvidos no metabolismo glicêmico e lipídico. Avaliou-se também o aspecto histológico e a inflamação do tecido hepático por quantificação das citocinas IL-6, TNF-alfa e IL-1beta. A dieta rica em gordura conduziu a um aumento dos depósitos de gordura intra-abdominal, hiperglicemia e hiperlipidemia. Os animais também apresentavam esteatohepatite, com aumento de citocinas pró-inflamatórias e diminuição na expressão de PGC-1alfa no tecido hepático. O envolvimento do PGC-1alfa na produção de mediadores inflamatórios por hepatócitos foi avaliado em células HepG2 utilizando RNA de interferência (RNAi). O knockdown da expressão de PGC-1alfa causou aumento na expressão e liberação de IL-6 em hepatócitos via aumento na fosforilação de IkBalfa e consequente ativação do NFkB. Portanto, nossos dados mostram que o PGC-1alfa inibe a produção de mediadores inflamatórios (IL-6) em hepatócitos, e fornecem novas evidências das conexões existentes entre as vias metabólicas e imunes