Insulin depletion leads to adipose-specific cell death in obese but not lean mice

Mutation of the obese gene produces obesity, hyperinsulinemia, and compensatory “overexpression” of the defective gene. As insulin activates obese gene expression, it seemed possible that hyperinsulinemia might be responsible for overexpression of the gene. To address this question we rapidly neutralized circulating insulin by injection of an insulin antibody. Unexpectedly, insulin depletion in obese (ob/ob or db/db) mice caused massive adipose RNA degradation confirmed by histological analysis to result from adipocyte cell death by a largely necrotic mechanism. This effect was not observed in lean littermates and was completely corrected by coadministration of insulin. Comparison of multiple tissues demonstrated that the effect was restricted to adipose tissue. Insulin depletion in obese mice by administration of streptozotocin also led to cell death, but this death was less extensive and appeared to be apoptotic in mechanism. Thus insulin may promote the survival side of the physiological balance between adipocyte survival and death.

Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity

Perilipin coats the lipid droplets of adipocytes and is thought to have a role in regulating triacylglycerol hydrolysis. To study the role of perilipin in vivo, we have created a perilipin knockout mouse. Perilipin null (peri−/−) and wild-type (peri+/+) mice consume equal amounts of food, but the adipose tissue mass in the null animals is reduced to ≈30% of that in wild-type animals. Isolated adipocytes of perilipin null mice exhibit elevated basal lipolysis because of the loss of the protective function of perilipin. They also exhibit dramatically attenuated stimulated lipolytic activity, indicating that perilipin is required for maximal lipolytic activity. Plasma leptin concentrations in null animals were greater than expected for the reduced adipose mass. The peri−/− animals have a greater lean body mass and increased metabolic rate but they also show an increased tendency to develop glucose intolerance and peripheral insulin resistance. When fed a high-fat diet, the perilipin null animals are resistant to diet-induced obesity but not to glucose intolerance. The data reveal a major role for perilipin in adipose lipid metabolism and suggest perilipin as a potential target for attacking problems associated with obesity.

Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.

Mutations in the obese (ob) gene lead to obesity. This gene has been recently cloned, but the factors regulating its expression have not been elucidated. To address the regulation of the ob gene with regard to body weight and nutritional factors, Northern blot analysis was used to assess ob mRNA in adipose tissue from mice [lean, obese due to diet, or genetically (yellow agouti) obese] under different nutritional conditions. ob mRNA was elevated in both forms of obesity, compared to lean controls, correlated with elevations in plasma insulin and body weight, but not plasma glucose. In lean C57BL/6J mice, but not in mice with diet-induced obesity, ob mRNA decreased after a 48-hr fast. Similarly, in lean C57BL/6J controls, but not in obese yellow mice, i.p. glucose injection significantly increased ob mRNA. For up to 30 min after glucose injection, ob mRNA in lean mice significantly correlated with plasma glucose, but not with plasma insulin. In a separate study with only lean mice, ob mRNA was inhibited >90% by fasting, and elevated approximately 2-fold 30 min after i.p. injection of either glucose or insulin. These results suggest that in lean animals glucose and insulin enhance ob gene expression. In contrast to our results in lean mice, in obese animals ob mRNA is elevated and relatively insensitive to nutritional state, possibly due to chronic exposure to elevated plasma insulin and/or glucose.

Sistemática de transformação: desenvolvimento teórico para o alinhamento entre estratégia e cultura organizacional nos projetos de Lean

Desde o final do Século XX e início do Século XXI, estudos analisam a elevada taxa de insucesso ou insatisfação com os Programas de Lean. Esta taxa tem se demonstrado demasiadamente elevada, variando entre 66% e 90%. Como efeito deste insucesso, tem-se o desperdício de tempo, dinheiro, recursos e, talvez o pior, tem-se a propagação do medo nos agentes de mudança em empreitar novas iniciativas de mudança. Estudos apontam a falta de alinhamento de tais projetos com a Cultura Organizacional como uma das questões fundamentais deste insucesso. Partindo desta temática de pesquisa, este ensaio teórico pode ser caracterizado como uma abordagem qualitativa de análise do problema, de natureza básica de pesquisa buscando gerar conhecimentos novos e úteis às organizações, sem aplicação prática prevista neste primeiro estágio de pesquisa. A fonte de evidências para sustentar o modelo proposto foi revisão dos estudos de caso encontrados na literatura, sendo utilizadas tanto uma Revisão Bibliográfica Sistemática (RBS) quanto Exploratória, de tal maneira a buscar o \"estado da arte\" no campo de estudo. A Fundamentação Teórica do trabalho é baseada na literatura de quatro grandes campos de estudo: (i) Estratégia, (ii) Lean, (iii) Cultura Organizacional e (iv) Gestão de Mudanças. A RBS tem foco nas interseções destes grandes campos, agregando 190 trabalhos internacionais. Por sua vez, a Revisão Exploratória traz algumas das principais referências dos três campos de estudo, como: Edgar Schein, John Kotter, Kim Cameron, Robert Quinn, David Mann, dentre outros. Desta maneira, este trabalho estudou a influência da cultura organizacional nos projetos de transformação e, a partir da ruptura com a teoria atual, construiu e propôs uma sistemática teórica, intitulada de \"Sistemática de Transformação\" (ou simplesmente \"Sistemática T\"), a qual propõe o alinhamento entre três dimensões: Estratégia, Projeto de Transformação e Cultura Organizacional. Fazendo uso desta sistemática, é esperado que os agentes de mudança consigam ter um planejamento mais eficaz do processo de diagnóstico, avaliação e gestão da cultura organizacional alinhado à Estratégia e também ao Projeto de Transformação da organização, com ênfase nos Programas de Lean. A proposição e uso desta sistemática pode favorecer tanto a discussão acadêmica na área de Gestão de Operações sobre o tema, quanto fornecer subsídios para aplicações práticas mais eficazes.

Conceptos Clave de Operaciones y Lean Sigma para PYMES

Este libro analiza la metodología Lean Sigma para reducir Costes, aumentar la Calidad y reducir los Tiempos, de forma que aumente la rentabilidad empresarial.

Logiche di lean production nella cantieristica navale: considerazioni generali e applicazioni nella progettazione della linea di assemblaggio per il modello Ferretti 450.

L'elaborato di tesi è stato redatto durante un progetto semestrale in Ferretti Group riguardante il campo di applicazione delle logiche della lean production all'interno del settore della cantieristica navale. Il primo capitolo contiene una descrizione dell'evoluzione del Gruppo Ferretti, dalla nascita fino ai giorni nostri. Nel secondo capitolo vi è una ampia descrizione della filosofia lean e delle tecniche e egli strumenti usati nei contesti aziendali; il terzo capitolo nasce invece per sintetizzare una serie di articoli accademici inerenti al tema del "lean shipbuilding". Infine il quarto capitolo descrive alcune attività eseguite in azienda, a supporto della nascita di una nuova linea di assemblaggio per il modello Ferretti 450.

Clave de ferias ò Prontuario manual para la inteligencia de las fechas de los monumentos de España : util para juezes, abogados, archiverso y demàs personas, que lean historias y usen de privilegios, instrumentos ù otras memorias antiguas ... /

Mode of access: Internet.

LEAN'S COLLECTANIA;

Mode of access: Internet.

California trials with lean concrete base (LCB) /

Mode of access: Internet.

The fat years and the lean.

Mode of access: Internet.

Quantification of lean bodyweight

Background: Lean bodyweight (LBW) has been recommended for scaling drug doses. However, the current methods for predicting LBW are inconsistent at extremes of size and could be misleading with respect to interpreting weight-based regimens. Objective: The objective of the present study was to develop a semi-mechanistic model to predict fat-free mass (FFM) from subject characteristics in a population that includes extremes of size. FFM is considered to closely approximate LBW. There are several reference methods for assessing FFM, whereas there are no reference standards for LBW. Patients and methods: A total of 373 patients (168 male, 205 female) were included in the study. These data arose from two populations. Population A (index dataset) contained anthropometric characteristics, FFM estimated by dual-energy x-ray absorptiometry (DXA - a reference method) and bioelectrical impedance analysis (BIA) data. Population B (test dataset) contained the same anthropometric measures and FFM data as population A, but excluded BIA data. The patients in population A had a wide range of age (18-82 years), bodyweight (40.7-216.5kg) and BMI values (17.1-69.9 kg/m(2)). Patients in population B had BMI values of 18.7-38.4 kg/m(2). A two-stage semi-mechanistic model to predict FFM was developed from the demographics from population A. For stage 1 a model was developed to predict impedance and for stage 2 a model that incorporated predicted impedance was used to predict FFM. These two models were combined to provide an overall model to predict FFM from patient characteristics. The developed model for FFM was externally evaluated by predicting into population B. Results: The semi-mechanistic model to predict impedance incorporated sex, height and bodyweight. The developed model provides a good predictor of impedance for both males and females (r(2) = 0.78, mean error [ME] = 2.30 x 10(-3), root mean square error [RMSE] = 51.56 [approximately 10% of mean]). The final model for FFM incorporated sex, height and bodyweight. The developed model for FFM provided good predictive performance for both males and females (r(2) = 0.93, ME = -0.77, RMSE = 3.33 [approximately 6% of mean]). In addition, the model accurately predicted the FFM of subjects in population B (r(2) = 0.85, ME -0.04, RMSE = 4.39 [approximately 7% of mean]). Conclusions: A semi-mechanistic model has been developed to predict FFM (and therefore LBW) from easily accessible patient characteristics. This model has been prospectively evaluated and shown to have good predictive performance.

Anthropometry profiles of elite rugby players: quantifying changes in lean mass

Objective: To demonstrate the utility of a practical measure of lean mass for monitoring changes in the body composition of athletes. Methods: Between 1999 and 2003 body mass and sum of seven skinfolds were recorded for 40 forwards and 32 backs from one Super 12 rugby union franchise. Players were assessed on 13 (7) occasions ( mean (SD)) over 1.9 (1.3) years. Mixed modelling of log transformed variables provided a lean mass index (LMI) of the form mass/skinfolds(x), for monitoring changes in mass controlled for changes in skinfold thickness. Mean effects of phase of season and time in programme were modelled as percentage changes. Effects were standardised for interpretation of magnitudes. Results: The exponent x was 0.13 for forwards and 0.14 for backs ( 90% confidence limits +/- 0.03). The forwards had a small decrease in skinfolds ( 5.3%, 90% confidence limits +/- 2.2%) between preseason and competition phases, and a small increase ( 7.8%, 90% confidence limits +/- 3.1%) during the club season. A small decrease in LMI (similar to 1.5%) occurred after one year in the programme for forwards and backs, whereas increases in skinfolds for forwards became substantial (4.3%, 90% confidence limits +/- 2.2%) after three years. Individual variation in body composition was small within a season (within subject SD: body mass, 1.6%; skinfolds, 6.8%; LMI, 1.1%) and somewhat greater for body mass (2.1%) and LMI (1.7%) between seasons. Conclusions: Despite a lack of substantial mean changes, there was substantial individual variation in lean mass within and between seasons. An index of lean mass based

Responses in carcass lean pH at 24 hours post-mortem in lines of Large White pigs selected for growth rate on a fixed ration over a set time

A restricted maximum likelihood analysis applied to an animal model showed no significant differences (P > 0.05) in pH value of the longissimus dorsi measured at 24 h post-mortem (pH24) between high and low lines of Large White pigs selected over 4 years for post-weaning growth rate on restricted feeding. Genetic and phenotypic correlations between pH24 and production and carcass traits were estimated using all performance testing records combined with the pH24 measurements (5.05–7.02) on slaughtered animals. The estimate of heritability for pH24 was moderate (0.29 ± 0.18). Genetic correlations between pH24 and production or carcass composition traits, except for ultrasonic backfat (UBF), were not significantly different from zero. UBF had a moderate, positive genetic correlation with pH24 (0.24 ± 0.33). These estimates of genetic correlations affirmed that selection for increased growth rate on restricted feeding is likely to result in limited changes in pH24 and pork quality since the selection does not put a high emphasis on reduced fatness.

Change in lean body mass Is a major determinant of change in areal bone mineral density of the proximal femur: A 12-year observational study

Our objective was to assess the contribution of lean body mass (LBM) and fat body mass (FBM) to areal bone mineral density (aBMD) in women during the years surrounding menopause. We used a 12-year observational design. Participants included 75 Caucasian women who were premenopausal, 53 of whom were available for follow-up. There were two measurement periods: baseline and 12-year follow-up. At both measurement periods, bone mineral content and aBMD of the proximal femur, posterior-anterior lumbar spine, and total body was assessed using dual-energy X-ray absorptiometry (DXA). LBM and FBM were derived from the total-body scans. General health, including current menopausal status, hormone replace therapy use, medication use, and physical activity, was assessed by questionnaires. At the end of the study, 44% of the women were postmenopausal. After controlling for baseline aBMD, current menopausal status, and current hormone replacement therapy, we found that change in LBM was independently associated with change in aBMD of the proximal femur (P = 0.001). The cross-sectional analyses also indicated that LBM was a significant determinant of aBMD of all three DXA-scanned sites at both baseline and follow-up. These novel longitudinal data highlight the important contribution of LBM to the maintenance of proximal femur bone mass at a key time in women's life span, the years surrounding menopause.