bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinoic Acid Treatment Increases Lipid Oxidation Capacity in Skeletal Muscle of Mice
Authors: Amengual Jaume , Ribot Joan , Bonet M. Luisa , Palou Andreu 
Published: January 2008

Objective: All‐trans retinoic acid (ATRA), a carboxylic form of vitamin A, favors in mice a mobilization of body fat reserves that correlates with an increment of oxidative and thermogenic capacity in adipose tissues. The objective of this study has been to investigate the effect of ATRA treatment on skeletal muscle capacity for fatty‐acid catabolism.Methods and Procedures: Tissue composition and gene expression related to lipid and oxidative metabolism were analyzed in skeletal muscle of mice acutely treated with ATRA or vehicle (olive oil).Results: ATRA treatment triggered a dose‐dependent increase in the muscle mRNA expression levels of selected enzymes, transporters and transcription factors involved in fatty‐acid oxidation, respiration, and thermogenesis namely: muscle‐type carnitine palmitoyltransferase 1, acyl CoA oxidase 1, subunit II of cytochrome oxidase, uncoupling protein 3, peroxisome proliferator–activated receptor‐γ co‐activator −1α and peroxisome proliferator–activated receptor‐δ (PPARδ). The treatment also resulted in the upregulation of the mRNA levels of acetyl‐CoA carboxylase 2 (ACC2), a key regulatory enzyme for mitochondrial fatty‐acid oxidation in muscle. Skeletal muscle protein levels of PPARδ and retinoid X receptor γ, a partner for many nuclear receptors involved in lipid metabolism, were increased after ATRA treatment. Muscle lipid content was decreased.Discussion: These results indicate that ATRA treatment increases the capacity of skeletal muscle for fatty‐acid oxidation. Knowledge of nutrients or nutrient‐derivatives capable of enhancing oxidative metabolism in muscle and other tissues can contribute to new avenues of prevention and treatment of obesity and related disorders.
Scanning Electron Microscopic Analysis of Intramyocellular Lipid Droplets in an Animal Model of Type 2 Diabetes
Authors: Fraenkel Merav , Weiss Ram , Leizerman Ilit , Anaby Debbie , Golomb Eliahu , Leibowitz Gil , Kaiser Nurit 
Published: January 2008

Objective: To evaluate the accumulation pattern of intramyocellular lipids (IMCLs) in striated muscle during the development and progression of diabetes, using a novel scanning electron microscopic method.Methods and Procedures: Hyperglycemia was induced by feeding diabetes‐prone (DP) Psammomys obesus a high‐energy (HE) diet. Lipid accumulation within gastrocnemius muscle fibers was assessed in formalin‐fixed muscle samples during the development of hyperglycemia using high resolution imaging in a scanning electron microscope. We evaluated the temporal relationship between changes in IMCL quantity and morphology and the altered glucose metabolism and assessed the effect of reversal of hyperglycemia on IMCL level and morphology. Diabetes‐resistant (DR) P. obesus served as controls.Results: Lipid accumulation in the muscle fibers of DP animals was increased with the development of hyperglycemia. This was characterized by increased lipid density as well as by an abundance of large lipid droplets. Reversal of the phenotype resulted in the disappearance of large lipid droplets. The IMCL level and the distribution of lipid droplet size were similar in muscles of both the normoglycemic DR and DP animals, with an abundance of small lipid droplets. This profile was changed following a HE diet only in the DP animals.Discussion: Lipid accumulation in the muscle of P. obesus during the development of hyperglycemia is characterized by increased quantity and accumulation of large lipid droplets. These changes were reversible upon normalization of blood glucose. The evaluated methodology is a useful tool for the study of the dynamics of lipid accumulation in different metabolic conditions.
Parental Recognition of Overweight in School‐age Children
Authors: West Delia S. , Raczynski James M. , Phillips Martha M. , Bursac Zoran , Gauss C. Heath , Montgomery Brooke E.E. 
Published: January 2008

Objective: Examine the accuracy of parental weight perceptions of overweight children before and after the implementation of childhood obesity legislation that included BMI screening and feedback.Methods and Procedures: Statewide telephone surveys of parents of overweight (BMI ≥ 85th percentile) Arkansas public school children before (n = 1,551; 15% African American) and after (n = 2,508; 15% African American) policy implementation were examined for correspondence between parental perception of child's weight and objective classification.Results: Most (60%) parents of overweight children underestimated weight at baseline. Parents of younger children were significantly more likely to underestimate (65%) than parents of adolescents (51%). Overweight parents were not more likely to underestimate, nor was inaccuracy associated with parental education or socioeconomic status. African‐American parents were twice as likely to underestimate as whites. One year after BMI screening and feedback was implemented, the accuracy of classification of overweight children improved (53% underestimation). African‐American parents had significantly greater improvements than white parents (P < 0.0001).Discussion: Parental recognition of childhood overweight may be improved with BMI screening and feedback, and African‐American parents may specifically benefit. Nonetheless, underestimation of overweight is common and may have implications for public health interventions.
Pancreatic Ectopic Fat Is Characterized by Adipocyte Infiltration and Altered Lipid Composition
Authors: Pinnick Katherine E. , Collins Stephan C. , Londos Constantine , Gauguier Dominique , Clark Anne , Fielding Barbara A. 
Published: January 2008

Objective: Sustained exposure to lipids is deleterious for pancreatic islet function. This could be mediated through increased pancreatic fat following increased dietary fat and in obesity, which has implications for the onset of type 2 diabetes. The aims of this study were to determine changes in extent and composition of pancreatic, hepatic, and visceral fat in mice fed a high‐fat diet (HFD, 40% by weight) compared with a control diet (5% fat) of similar fatty acid composition, and to compare composition and extent of pancreatic fat in human type 2 diabetes.Methods and Procedures: Mice were fed HFD for 3 or 15 weeks. Human postmortem pancreas was examined from subjects with type 2 diabetes (n = 9) and controls (n = 7). Tissue lipid content and composition were determined by gas chromatography and pancreatic adipocyte infiltration quantified by morphometry.Results: Pancreatic triacylglycerol (TG) content was 20× greater (P < 0.05) in HFD mice and there were more pancreatic perilipin‐positive adipocytes compared with controls after 15 weeks. The proportions of 18:1n −9 and 18:2n −6 in pancreatic TG and the 20:4n −6/18:2n −6 ratio in phospholipids, were higher (both P < 0.05) after HFD compared with controls. Human pancreatic TG content was correlated with the proportion of pancreatic perilipin‐positive adipocytes (r = 0.64, P < 0.05) and associated with unsaturated fatty acid enrichment (P < 0.05).Discussion: Adipocyte infiltration in pancreatic exocrine tissue is associated with high‐fat feeding in mice and pancreatic TG content in humans. This alters the fatty acid milieu of the islet which could contribute to islet dysfunction.
ACE Inhibition and AT1 Receptor Blockade Prevent Fatty Liver and Fibrosis in Obese Zucker Rats
Authors: Toblli Jorge E. , Muñoz Marina C. , Cao Gabriel , Mella José , Pereyra Lisandro , Mastai Ricardo 
Published: January 2008

Objective: Non‐alcoholic steatohepatitis (NASH), which is a common liver disease in industrialized countries, is associated with obesity, hypertension, and type‐2 diabetes (metabolic syndrome). Since angiotensin II (ANG II) has been suggested to play an important role in liver inflammation and fibrosis, the purpose of this study was to investigate whether therapy against renin‐angiotensin system (RAS) may provide some beneficial effect in liver of an animal model of metabolic syndrome.Methods and Procedures: For 6 months, obese Zucker rats (OZRs) were treated as follows: OZR‐group, OZR + Perindopril (P) group, OZR + Irbesartan (IRB) group, OZR + Amlodipine (AML) group, and lean Zucker rats (LZRs) group as a control. Livers were evaluated by immunohistochemistry techniques using corresponding antibodies.Results: All treated groups showed a similar reduction in blood pressure compared to untreated OZR. Therapy either with IRB or P improves insulin sensitivity and reduces hepatic enzyme level with respect to untreated OZR. Conversely, AML failed to modify both parameters. Untreated OZR displayed higher hepatic ANG II levels and steatosis together with a marked increase in tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and transforming growth factor‐β1 (TGF‐β1) level compared to LZR. Following RAS inhibition either by P or IRB, a significant reduction (P < 0.01) in the immunostaining of TNF‐α, IL‐6 and TGF‐β1 compared to untreated OZR was observed.Discussion: These results indicate that ANG II expression is increased in the liver of these animals with steatohepatitis. Furthermore, RAS control by either angiotensin‐converting enzyme inhibition or AT1 receptor blockade seems to provide a beneficial modulation concerning the inflammatory response to liver injury in this model. Consequently, blockade of RAS could be a new approach to prevent or to treat patients with NASH.
Place of Residence and Obesity in 1,578,694 Young Swedish Men Between 1969 and 2005
Authors: Neovius Martin , Rasmussen Finn 
Published: January 2008

Objective: To compare prevalence of overweight and obesity in young adult men from rural areas with those from urban areas of Sweden over three decades.Methods and Procedures: Eighty‐two percent of the Swedish male population at military conscription age between 1969 and 2005 (n = 1,578,694; 18.3 ± 0.4 years) was grouped by urban, semiurban, and rural place of residence. BMI was calculated from measured height and weight. Comparisons were made with and without adjustments for parental education, socioeconomic position (SEP), and intelligence quotient (IQ).Results: During the study period, the prevalence of obesity more than quintupled from 0.9–5.1%, while overweight tripled from 7.1–20.5% (P < 0.0001). An urban–rural gradient was observed within all socioeconomic and education strata. After adjustment for SEP, IQ, parental education level, and testing year, the odds ratios (ORs) were 1.28 (1.23–1.34) and 1.20 (1.18–1.22) for obesity and overweight, respectively, in a rural compared to an urban area. The corresponding ORs for semiurban place of residence were 1.16 (1.13–1.19) and 1.11 (1.10–1.12), respectively. Significant effect modification by time was seen, with evidence of an increasing gradient until the early 1990s (P < 0.001).Discussion: A strong and persisting gradient of increasing overweight and obesity from urban to rural areas was observed that could not be explained by individual or family‐related factors such as IQ, parental education level, or SEP. These results indicate the presence of strong environmental or contextual obesogenic factors affecting the energy balance of people in rural areas more negatively than those in urban communities.
Sex‐differential Expression of Metabolism‐related Genes in Response to a High‐fat Diet
Authors: Priego Teresa , Sánchez Juana , Picó Catalina , Palou Andreu 
Published: January 2008

Objective: The aim of this work was to determine the sex‐associated differences in the expression of genes related to lipid metabolism and fuel partitioning in response to a high‐fat (HF) diet in rats, and whether this is linked to the higher tendency of males to suffer from metabolic disorders.Methods and Procedures: Male and female Wistar rats were fed for 6 months on a normal‐fat (NF) or an HF diet. Body weight, fat depot weight, lipid concentration in liver, blood metabolites, and the expression of genes involved in fuel metabolism and partitioning in the liver, white adipose tissue (WAT), and skeletal muscle were measured.Results: Female rats fed on an HF diet gained more weight and had a greater increase in the adiposity index than male rats, while the circulating insulin levels remained unaltered; these animals also showed an increased expression of genes related to the energy influx in WAT and with fat utilization in skeletal muscle. Male but not female rats showed increased hepatic peroxisome proliferator–activated receptor‐α (PPAR‐α) and CPT1L mRNA expression, suggesting enhanced lipid handling and oxidation by this organ, and have a higher triacylglycerol content in liver. Male rats under the HF diet also displayed higher blood insulin levels.Discussion: These results show sex‐dependent differences in lipid handling and partitioning between tissues in response to an HF diet, with females showing a higher capacity for storing fat in adipose tissue and for oxidizing fatty acids in muscle. These adaptations can help to explain the lower tendency of females to suffer from obesity‐linked disorders under the conditions of an HF diet.
Liver Steatosis in Obese Prepubertal Children: A Possible Role of Insulin Resistance
Authors: D'Adamo Ebe , Impicciatore Mario , Capanna Rita , Marcovecchio M. Loredana , Masuccio Fabio G. , Chiarelli Francesco , Mohn Angelika A. 
Published: January 2008

Objective: To determine whether in obese prepubertal children insulin resistance (IR) is associated with the development of liver steatosis.Methods and Procedures: Cross‐sectional study evaluating the prevalence of liver steatosis in 100 severely obese prepubertal children and comparing IR indexes between children with (group 1) and without steatosis (group 2). Furthermore, IR indexes were compared to values of 50 normal weight children. Fasting blood samples were collected for the evaluation of liver function tests, lipid profile, plasma glucose, and insulin levels. All children underwent an oral glucose tolerance test and anthropometric measurements. Hepatic ultrasound was performed according to international criteria and by one single operator. Analysis was performed by Mann–Whitney U‐test, Pearson correlation, and logistic regression.Results: Liver steatosis was found in 52% obese children and was equally distributed between the two sexes. Obese children were more insulin resistant when compared to controls (homeostasis model assessment of IR (HOMA‐IR): P = 0.0001; whole body insulin sensitivity index (WBISI): P = 0.0005; fasting glucose/fasting insulin ratio (G/I): P = 0.0001), and group 1 presented an even higher degree of IR when compared to group 2 (HOMA‐IR P = 0.0001; WBISI P = 0.0004; G/I P = 0.0001). The area under the curve (AUC) for insulin was significantly higher in group 1 when compared to group 2, while no difference was found in the AUC for glucose. There was no association between IR and adiposity indexes (P >0.05). The role of IR as a predictor for the development of steatosis was analyzed by multiple logistic regression, which documented that IR indexes were significantly related to steatosis independently of BMI‐SDS.Discussion: Liver steatosis is an emerging problem in prepubertal severely obese children, and it appears to be an association between liver steatosis and IR in these subjects.
INSIG2 Polymorphism Is Neither Associated With BMI Nor With Phenotypes of Lipoprotein Metabolism
Authors: Boes Eva , Kollerits Barbara , Heid Iris M. , Hunt Steven C. , Pichler Michaela , Paulweber Bernhard , Coassin Stefan , Adams Ted D. , Hopkins Paul N. , Lingenhel Arno , Wagner Stefanie A. , Kronenberg Florian 
Published: January 2008

Objective: A previous epidemiological study showed an association of the insulin‐induced gene 2 (INSIG2) gene with BMI. Additionally, experimental investigations in animals and cell culture provided evidence that this gene might be involved in lipoprotein and free fatty acid (FFA) metabolism. Therefore, the aim of this study was to examine the association between the rs7566605 variant near the INSIG2 gene and BMI and to extend it to other quantitative measures of obesity, as well as parameters of lipoprotein and FFA metabolism.Methods and Procedures: We genotyped rs7566605 in a group of severely obese white patients (n = 1,026) with an average BMI of 46.0 kg/m2 and a control group (n = 818) from Utah, as well as in the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study from Austria, which is based on a healthy working population (n = 1,696).Results: We observed no difference in the genotype frequency of rs7566605 of INSIG2 between obese subjects and population‐based controls from Utah. Furthermore, we did not find evidence of an association with measures of body composition (BMI, waist, waist‐to‐hip ratio, percentage body fat, amount of visceral and subcutaneous abdominal adipose fat) or lipoprotein metabolism (total cholesterol, low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) cholesterol, triglycerides, and FFAs) in the Utah study population or in the independent SAPHIR study.Discussion: Our results do not support an association of the INSIG2 gene with the regulation of body weight or parameters related to lipoprotein metabolism.
What Is the Accurate Prevalence of Obesity in Sweden in the 21st Century? Methodological Experiences From the Skaraborg Project
Authors: Nyholm Maria , Gullberg Bo , Råstam Lennart , Lindblad Ulf 
Published: January 2008

Objective: To examine the impact of non‐response to self‐reported body weight and height in health questionnaires for the estimation of obesity prevalence.Methods and Procedures: A cross‐sectional population‐based health survey in the community of Vara with 16,009 residents (in year 2002) in South‐western Sweden. Participants randomly selected in strata by sex and age among residents being 30–74 years old were consecutively invited to the local health care center for a health examination, including two visits. Self‐reported information on body weight and height were obtained by health questionnaires at the first visit, and measured information on both variables at the second visit. For this study 1,809 subjects (904 men and 905 women) completed both visits (participation rate 81%), and a nurse measured body weight and height of all at visit two. Participants not self‐reporting body weight and/or height at the first visit were defined as non‐responders.Results: Both male and female non‐responders were significantly older than responders. Female non‐responders had significantly higher BMI (29.8 ± 5.8 kg/m2) than female responders (26.6 ± 5.3 kg/m2), (P < 0.001). No similar findings were seen in men. Non‐responders were more likely to be obese than responders both in men (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.03–4.11) and in women (OR 2.24, 95% CI 1.25–4.02).Discussion: Non‐responders to self‐reported body weight and height in health questionnaires contribute to the underestimation of obesity. Measured body weight and height are to prefer when describing the accurate prevalence of obesity in populations.
Genetic Influences on Growth Traits of BMI: A Longitudinal Study of Adult Twins
Authors: Hjelmborg Jacob v.B. , Fagnani Corrado , Silventoinen Karri , McGue Matt , Korkeila Maarit , Christensen Kaare , Rissanen Aila , Kaprio Jaakko 
Published: January 2008

Objective: To investigate the interplay between genetic factors influencing baseline level and changes in BMI in adulthood.Methods and Procedures: A longitudinal twin study of the cohort of Finnish twins (N = 10,556 twin individuals) aged 20–46 years at baseline was conducted and followed up 15 years. Data on weight and height were obtained from mailed surveys in 1975, 1981, and 1990.Results: Latent growth models revealed a substantial genetic influence on BMI level at baseline in males and females (heritability (h2) 80% (95% confidence interval 0.79–0.80) for males and h2 = 82% (0.81, 0.84) for females) and a moderate‐to‐high influence on rate of change in BMI (h2 = 58% (0.50, 0.69) for males and h2 = 64% (0.58, 0.69) for females). Only very weak evidence for genetic pleiotropy was observed; the genetic correlation between baseline and rate of change in BMI was very modest (−0.070 (–0.13, −0.068) for males and 0.04 (0.00, 0.08) for females.Discussion: Our population‐based results provide a basis for identifying genetic variants for change in BMI, in particular weight gain. Furthermore, they demonstrate for the first time that such genetic variants for change in BMI are likely to be different from those affecting level of BMI.
Association of the MC4R V103I Polymorphism With the Metabolic Syndrome: The KORA Study
Authors: Heid Iris M. , Vollmert Caren , Kronenberg Florian , Huth Cornelia , Ankerst Donna P. , Luchner Andreas , Hinney Anke , Brönner Günter , Wichmann H.‐E. , Illig Thomas , Döring Angela , Hebebrand Johannes 
Published: January 2008

Objective: Epidemiological studies showing an association between the melanocortin‐4‐receptor (MC4R) 103I variant (rs2229616) and decreased BMI are complemented by functional studies; these suggest a mechanism for appetite regulation and a linkage signal for physical activity and dietary intake for the region encompassing the MC4R. This study aims to provide epidemiological evidence for showing the association of this polymorphism with features of the metabolic syndrome and with parameters related to energy expenditure and dietary habits as potential mediators.Methods and Procedures: We analyzed this polymorphism in 7,888 adults of a population‐based cross‐sectional study applying regression‐based statistical models.Results: Carriers of the MC4R 103I (3.7%) exhibited a significantly decreased waist circumference (–1.46 cm, P = 0.020), decreased glycosylated hemoglobin (HbA1c) (–0.09%, P = 0.040), and increased HDL‐cholesterol (HDL‐C) (+1.76 mg/dl, P = 0.056), but no change in blood pressure. The odds of having three or more components of the metabolic syndrome were substantially reduced among carriers of MC4R 103I (odds ratio (OR) = 0.46, P = 0.003). Controlling for BMI reduced the HbA1c and HDL‐C association. Mediator analyses revealed a borderline association of MC4R 103I with carbohydrate intake (OR = 1.26, P = 0.059) possibly mediating association with leanness.Discussion: Our representative study of well‐phenotyped Europeans is the first to describe the association of the MC4R V103I with the metabolic syndrome and with a nutrient‐related phenotype. Our data support the idea that this polymorphism plays a role in appetite regulation that not only affects BMI, but also other features of the metabolic syndrome. It further establishes that the association of the MC4R V103I with obesity and related phenotypes is genuine.