ABSTRACT
Extracellular signal-regulated kinase 1 and 2 (ERK1/2) have been implicated as important regulators of metabolic homeostasis. Here we generated a new mouse model with genetic deletion of two ERK1/2 phosphatases, dual specificity phosphatase (DUSP) 6 and 8, to further define the role of ERK1/2 in obesity development. Dusp6/8 double-null mice demonstrated elevated ERK1/2 phosphorylation in multiple tissues, without any change of phosphorylation of p38 and c-Jun N-terminal kinases (JNKs). Elevated ERK1/2 activity in Dusp6/8 double-null mice was associated with larger hearts and other organs, consistent with greater rate of cell proliferation in these mice. However, ERK1/2 activation was not sufficient to protect the mouse hearts from pathological hypertrophy and interstitial fibrosis following angiotensin II and phenylephrine stimulation. Interestingly, mice lacking DUSP6/8 were resistant to high-fat diet-induced obesity. Serum triglyceride, lipid content in the liver and visceral adipose tissues was also dramatically reduced in Dusp6/8 double-null mice. Furthermore, Dusp6/8 double-null mice had improved glucose tolerance. Mechanistically, we found out that elevated ERK1/2 activity increased the expression levels of genes involved in lipid metabolism and glucose homeostasis. Together, our data suggest that ERK1/2 play an essential role for the management of metabolic homeostasis.
Subject(s)
Dual Specificity Phosphatase 6/genetics , Dual-Specificity Phosphatases/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Obesity/genetics , Animals , Diet, High-Fat/adverse effects , Dual Specificity Phosphatase 6/metabolism , Dual-Specificity Phosphatases/metabolism , Enzyme Activation , Gene Deletion , Glucose/metabolism , Mice , Mice, Knockout , Obesity/diagnosis , Obesity/metabolism , PhosphorylationABSTRACT
O objetivo deste trabalho foi avaliar o efeito de duas dietas: baixo e alto nível de suplementação, fornecidas a vacas em estádio avançado de lactação sobre os aspectos produtivos, as características físico-químicas do leite e o perfil bioquímico sanguíneo. Foram utilizadas 12 vacas da raça Holandês, com média de 514kg de peso corporal, escore de condição corporal 3,5, produção de leite de 13 litros vaca-1 dia-1, com média de 349 dias de lactação. Os tratamentos foram: baixo e alto nível de suplementação para vacas mantidas em campo natural. Foram avaliados o peso vivo, o escore de condição corporal, a produção leiteira individual, as características físico-químicas e a contagem de células somáticas do leite (CCS), além do perfil bioquímico do sangue. As vacas, mesmo em estádio lactacional avançado, responderam ao aumento do aporte nutricional, com incrementos de ganho de peso, ganho de condição corporal e de produção de leite e produção leiteira corrigida para gordura, além de maiores teores de gordura e de sólidos totais. As demais características do leite e do sangue não foram alteradas. O aumento do aporte nutricional de vacas lactantes com estádio de lactação avançado pode ser uma opção viável para alcançar maior nível de produção leiteira e melhores condições físicas das vacas em sistemas de produção baseadas na utilização de pastagem, sem afetar adversamente a concentração dos componentes lácteos.
The trial aimed to verify the effects of two feeding supplements: low and high level supplementation given to cows at an extended lactation stage upon productive aspects, physical-chemical composition of milk and blood biochemical profile. Twelve lactating Holstein cows, with 514kg of body weight, body condition score of 3.5, yielding 13L milk cow-1 day-1 and approximately 349 days of lactation were used. Treatments were low or high level of supplementation for lactating cows grazing natural range pasture. Cow's body weight and body condition score, individual milk yield, physical and chemical characteristics and somatic cells count, besides biochemical blood profile were evaluated. Increased nutrient supply augmented body weight gain, body condition score, fat corrected milk, milk fat and total solids contents, but did not change the others milk components nor blood biochemical profile. Increasing nutrient supply for cows at an extended lactation might be a valuable option to match milk productivity and improved physical aspects of dairy cows kept on grazing systems, without adverse effects upon milk components yield.
ABSTRACT
OBJECTIVE: To determine the differences in quality of life between children with sickle cell disease and healthy immigrant children. DESIGN: Descriptive, comparative. METHOD: The quality of life of children with sickle cell disease between 5 and 15 years old being treated in the Emma Children's Hospital AMC in Amsterdam, the Netherlands, was assessed by using a questionnaire for parents (TNO-AZL Children's Quality of Life Questionnaire (TACQOL) parent form) if the child was between 8 and 15 years old. The study period was April-October 1998. The questionnaires were completed by 45 (parents of) patients. The results were compared with a healthy reference group of immigrant children. Statistical analysis was performed using the Student t-Test. RESULTS: Children with sickle cell disease as well as their parents scored signifcantly lower on the items general physical, motor and independent daily functioning and on occurrence of negative emotions. No significance was observed for the items cognitive functioning and school performance nor for social functioning or occurrence of positive emotions. CONCLUSIONS: In children, sickle cell disease leads to compromised physical and possibly also psychological wellbeing, as well as the experience of decreased independence in daily functioning, but not to compromised cognitive or social aspects of the quality of life. (AU)
Subject(s)
Child , Comparative Study , Female , Humans , Male , Adolescent , beta-Thalassemia/psychology , Anemia, Sickle Cell/psychology , Quality of Life/psychology , Africa , Caribbean Region/ethnology , Case-Control Studies , Hemoglobin SC Disease/psychology , Netherlands/epidemiology , Parents/psychology , Surveys and Questionnaires , Suriname/ethnologyABSTRACT
Supplies socio-economic information within the national context and reviews the situation of children with emphasis on child population, infant mortality and morbidity, nutrition status and education. Also reviews situation of women with emphasis on underlying and structural causes of problems that children and women face (AU)
Subject(s)
Adult , Female , Child , Humans , Women's Health , Child Health , Child Health , Infant Mortality , Morbidity , Saint LuciaABSTRACT
Supplies socio-economic information within the national context and reviews the situation of children with emphasis on child population, infant mortality and morbidity, nutrition status and education. Also reviews situation of women with emphasis on underlying and structural causes of problems that children and women face
