A Model of Binge‐Like Eating Behavior in Mice That Does Not Require Food Deprivation or Stress

Binge eating disorder (BED) is characterized by excessive food intake during a short period of time and is often associated with obesity. Mouse models of binge‐like eating behavior are lacking making it difficult to employ genetic models in the identification of mechanisms regulating excessive eating. We report a rapid and simple model to induce binge‐like eating behavior in mice that does not require food deprivation or exogenous stressors. Weekly 24 h access to a nutritionally complete high energy diet (HED), along with continuous access to standard chow, resulted in a significant increase in HED intake following its presentation compared to mice that had continuous access to both diets. Mice exhibiting binge‐like eating consumed one‐third of their normal total daily caloric intake within 2.5 h of HED presentation. Moreover, total 24‐h caloric intakes were increased by 50% in mice exhibiting binge‐like eating. Following repeated cycles, binge‐like eating of the HED was maintained over several weeks with no evidence of habituation or significant alterations in body weight and adiposity. Pharmacological evaluation of binge‐like eating behavior was performed using clinically employed compounds. Interestingly, binge‐like eating was dose‐dependently decreased by fluoxetine, but not baclofen or topiramate. These data support clinical validation of this mouse model of binge‐like eating behavior, as fluoxetine has been shown to reduce binge frequency in human subjects with BED. The availability of transgenic and knockout mice will allow for the determination of genes that are involved in the initiation and maintenance of binge‐like eating behavior.     

Effect of Orlistat in Obese Patients with Binge Eating Disorder

Objective: Binge eating disorder represents a significant public health problem, with up to 50% of weight loss program participants displaying this disorder. In previous studies with orlistat, patients with binge eating disorder were excluded. The goal of this study was to assess the efficacy of orlistat in obese patients with binge eating disorder. Research Methods and Procedures: Eighty‐nine patients with clinically diagnosed binge eating disorder and a BMI ≥ 30 kg/m² were randomized in double‐blind fashion to 24 weeks of treatment with 120 mg of orlistat or placebo three times daily, in combination with a mildly reduced‐calorie diet. Results: After 24 weeks, the mean weight loss from baseline for orlistat‐treated patients was significantly greater than for patients receiving placebo (?7.4% vs. ?2.3%; p = 0.0001) (intent‐to‐treat analysis). The overall Eating Disorder Inventory 2 score at week 24 was significantly lower in patients treated with orlistat than in those in the placebo group (p = 0.011) Discussion: Orlistat may be considered as part of the management for patients with obesity and binge eating disorder.     

Bingeing,Self‐restriction,and Increased Body Weight in Rats With Limited Access to a Sweet‐fat Diet

Objective: Prior research has shown that fasting alternated with a diet of standard rodent chow and a 10% sucrose solution produces bingeing on the sucrose, but animals remain at normal body weight. The present study investigated whether restricted access to a highly palatable combination of sugar and fat, without food deprivation, would instigate binge eating and also increase body weight. Methods and Procedures: Male rats were maintained for 25 days on one of four diets: (i) sweet‐fat chow for 2 h/day followed by ad libitum standard chow, (ii) 2‐h sweet‐fat chow only 3 days/week and access to standard chow the rest of the time, (iii) ad libitum sweet‐fat chow, or (iv) ad libitum standard chow. Results: Both groups with 2‐h access to the sweet‐fat chow exhibited bingeing behavior, as defined by excessively large meals. The body weight of these animals increased due to large meals and then decreased between binges as a result of self‐restricted intake of standard chow following binges. However, despite these fluctuations in body weight, the group with 2‐h access to sweet‐fat chow every day gained significantly more weight than the control group with standard chow available ad libitum. Discussion: These findings may have implications for the body weight fluctuations associated with binge‐eating disorder, as well as the relationship between binge eating and the obesity epidemic.     

Effect of Alginate on Satiation,Appetite, Gastric Function,and Selected Gut Satiety Hormones in Overweight and Obesity

Lack of control of food intake, excess size, and frequency of meals are critical to the development of obesity. The stomach signals satiation postprandially and may play an important role in control of calorie intake. Sodium alginate (based on brown seaweed Laminaria digitata) is currently marketed as a weight loss supplement, but its effects on gastric motor functions and satiation are unknown. We evaluated effects of 10 days treatment with alginate or placebo on gastric functions, satiation, appetite, and gut hormones associated with satiety in overweight or obese adults. We conducted a randomized, 1:1, placebo‐controlled, allocation‐concealed study in 48 overweight or obese participants with excluded psychiatric comorbidity and binge eating disorder. All underwent measurements of gastric emptying (GE), fasting, and postprandial gastric volumes (GVs), postprandial satiation, calorie intake at a free choice meal and selected gut hormones after 1 week of alginate (three capsules vs. matching placebo per day, ingested 30 min before the main meal). Six capsules were ingested with water 30 min before the GE, GV, and satiation tests on days 8–10. There were no treatment group effects on GE or volumes, gut hormones (ghrelin, cholecystokinin (CCK), glucagon‐like peptide‐1 (GLP‐1), peptide YY (PYY)), satiation, total and macronutrient calorie intake at a free choice meal. There was no difference detected in results between obese and overweight patients. Alginate treatment for a period of 10 days showed no effect on gastric motor functions, satiation, appetite, or gut hormones. These results question the use of short‐term alginate treatment for weight loss.     

Binge Eating,Body Image,Depression, and Self-Efficacy in an Obese Clinical Population

CARGILL, BRIAN R., MATTHEW M. CLARK, VINCENT PERA, RAYMOND S. NIAURA, AND DAVID B. ABRAMS. Binge eating, body image, depression, and self-efficacy in an obese clinical population. Obes Res. Objective: Binge eating disorder appears to be an important factor in obesity treatment. Researchers have proposed that specialized treatment programs be developed to address chronic binge eating behavior. This study was conducted to examine the relationships between binge eating, depression, body image, and self-efficacy. Based on related research, it was hypothesized that depression and negative body image would be greater for binge eaters whereas weight self-efficacy would be lower. Research Methods and Procedures: Subjects were 159 clinic patients participating in a multidisciplinary weight management program. Baseline measurements of binge eating status, body image and related eating behaviors, depression, and self-efficacy were obtained, whereas follow-up measures consisted of weight loss and attendance. Exploratory factor analyses were performed to obtain factors for items contained in the Eating Habits Questionnaire. Chi-square, t-tests, and logistic regression analyses determined relationships between binge eating, body image, depression, and self-efficacy. Results: Univariate comparisons indicated that increased perceptions of poor body image were significantly related to binge eating. Higher levels of depression and lower weight self-efficacy were related to binge eating, but the results were qualified after applying corrective statistics for multiple comparisons. A stepwise regression analysis indicated that body image, particularly characterized by a sense of shame and concern with public appearance, had the strongest relationship to binge eating among all the factors examined in this study. Discussion: These findings extend current understanding of the relationships between binge eating, body image, depression, and self-efficacy. The significance of body image, especially in relation to negative social consciousness, was determined when comparing several psychological and behavioral factors thought to influence binge eating. Further research is needed to determine the causal relationships between binge eating and the other factors examined in this study.     

The Relation between Erythrocyte Trans Fat and Triglyceride,VLDL- and HDL-Cholesterol Concentrations Depends on Polyunsaturated Fat

Background

Trans fatty acids (TFA) lower HDL and increase triglyceride concentrations while polyunsaturated fatty acids (PUFA) lower triglycerides and may decrease HDL concentrations. The effect of the interaction between trans fat and PUFA on lipids is uncertain.

Methods

Men and women (n = 1032) in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) study were included. Fatty acids in erythrocyte membranes were measured with gas chromatography while data on potential confounders were obtained from questionnaires. To test the interaction between total erythrocyte PUFA (ePUFA) and TFA (eTFA) on lipid concentrations we distributed eTFA into tertiles and dichotomized ePUFA at the median concentration.

Results

For the 1^st, 2^nd and 3^rd tertiles of eTFA, multivariate-adjusted means±s.e.m for HDL were 46.2±1.1, 46.3±1.1 and 45.5±1.0 mg/dL among those with low ePUFA, respectively, while they were 50.0±1.1, 46.9±1.1 and 44.7±1.1 mg/dL among those with high ePUFA, respectively (P for interaction = 0.01). For the 1^st, 2^nd and 3^rd tertiles of eTFA, multivariate-adjusted means±s.e.m for triglycerides were 178.6±11.3, 144.7±10.9 and 140.8±10.6, respectively, among those with low ePUFA, while they were 133.8±11.3, 145.7±10.9 and 149.3±11.5, respectively, among those with high ePUFA (P for interaction = 0.005). Results for VLDL were similar to those for triglycerides. No significant interactions were observed for LDL or total cholesterol.

Conclusions

The relation between trans fat and HDL, VLDL and triglycerides may depend on PUFA. The benefit of avoiding trans fat may be greater among individuals with higher PUFA intake. Supplementation with PUFA among individuals with relatively high trans fat intake may have limited benefits on lipid profiles.     

Chronic Aerobic Exercise Associated to Dietary Modification Improve Endothelial Function and eNOS Expression in High Fat Fed Hamsters

Obesity is epidemic in the western world and central adipose tissue deposition points to increased cardiovascular morbidity and mortality, independently of any association between obesity and other cardiovascular risk factors. Physical exercise has been used as non-pharmacological treatment to significantly reverse/attenuate obesity comorbidities. In this study we have investigated effects of exercise and/or dietary modification on microcirculatory function, body composition, serum glucose, iNOS and eNOS expression on 120 male hamsters treated for 12 weeks with high fat chow (HF, n = 30) starting on the 21^st day of birth. From week 12 to 20, animals were randomly separated in HF (no treatment change), return to standard chow (HFSC, n = 30), high fat chow associated to an aerobic exercise training program (AET) (HFEX, n = 30) and return to standard chow+AET (HFSCEX, n = 30). Microvascular reactivity in response to acetylcholine and sodium nitroprusside and macromolecular permeability increase induced by 30 minutes ischemia followed by reperfusion were assessed on the cheek pouch preparation. Total body fat and aorta eNOS and iNOS expression by immunoblotting assay were evaluated on the experimental day. Compared to HFSC and HFSCEX groups, HF and HFEX ones presented increased visceral fat [(mean±SEM) (HF)4.9±1.5 g and (HFEX)4.7±0.9 g vs. (HFSC)*3.0±0.7 g and (HFSCEX)*1.9±0.4 g/100 g BW]; impaired endothelial-dependent vasodilatation [Ach 10⁻⁸ M (HF)87.9±2.7%; (HFSC)*116.7±5.9%; (HFEX)*109.1±4.6%; (HFSCEX)*105±2.8%; Ach10⁻⁶ M (HF)95.3±3.1%; (HFSC)*126±6.2%; (HFEX)*122.5±2.8%; (HFSCEX)*118.1±4.3% and Ach10⁻⁴ M (HF)109.5±4.8%; (HFSC)*149.6±6.6%; (HFEX)*143.5±5.4% and (HFSCEX)*139.4±5.2%], macromolecular permeability increase after ischemia/reperfusion [(HF)40.5±4.2; (HFSC)*19.0±1.6; (HFEX)*18.6±2.1 and (HFSCEX)* 21.5±3.7 leaks/cm²), decreased eNOS expression, increased leptin and glycaemic levels. Endothelial-independent microvascular reactivity was similar between groups, suggesting that only endothelial damage had occurred. Our results indicate that an aerobic routine and/or dietary modification may cause significant improvements to high fat fed animals, diminishing visceral depots, increasing eNOS expression and reducing microcirculatory dysfunction.     

Systems genetic analysis of binge-like eating in a C57BL/6J x DBA/2J-F2 cross

Binge eating is a heritable trait associated with eating disorders and refers to the rapid consumption of a large quantity of energy-dense food that is, associated with loss of control and negative affect. Binge eating disorder is the most common eating disorder in the United States; however, the genetic basis is unknown. We previously identified robust mouse inbred strain differences between C57BL/6J and DBA/2J in binge-like eating of sweetened palatable food in an intermittent access, conditioned place preference paradigm. To map the genetic basis of changes in body weight and binge-like eating (BLE) and to identify candidate genes, we conducted quantitative trait locus (QTL) analysis in 128 C57BL/6J x DBA/2J-F2 mice combined with PheQTL and trait covariance analysis in GeneNetwork2 using legacy BXD-RI trait datasets. We identified a QTL on Chromosome 18 influencing changes in body weight across days in females (log of the odds [LOD] = 6.3; 1.5-LOD: 3–12 cM) that contains the candidate gene Zeb1. We also identified a sex-combined QTL influencing initial palatable food intake on Chromosome 5 (LOD = 5.8; 1.5-LOD: 21–28 cM) that contains the candidate gene Lcorl and a second QTL influencing escalated palatable food intake on Chromosome 6 in males (LOD = 5.4; 1.5-LOD: 50–59 cM) that contains the candidate genes Adipor2 and Plxnd1. Finally, we identified a suggestive QTL in females for slope of BLE on distal Chromosome 18 (LOD = 4.1; p = 0.055; 1.5-LOD: 23–35 cM). Future studies will use BXD-RI strains to fine map loci and support candidate gene nomination for gene editing.     

Learning to Eat Vegetables in Early Life: The Role of Timing,Age and Individual Eating Traits

Vegetable intake is generally low among children, who appear to be especially fussy during the pre-school years. Repeated exposure is known to enhance intake of a novel vegetable in early life but individual differences in response to familiarisation have emerged from recent studies. In order to understand the factors which predict different responses to repeated exposure, data from the same experiment conducted in three groups of children from three countries (n = 332) aged 4–38 m (18.9±9.9 m) were combined and modelled. During the intervention period each child was given between 5 and 10 exposures to a novel vegetable (artichoke puree) in one of three versions (basic, sweet or added energy). Intake of basic artichoke puree was measured both before and after the exposure period. Overall, younger children consumed more artichoke than older children. Four distinct patterns of eating behaviour during the exposure period were defined. Most children were “learners” (40%) who increased intake over time. 21% consumed more than 75% of what was offered each time and were labelled “plate-clearers”. 16% were considered “non-eaters” eating less than 10 g by the 5^th exposure and the remainder were classified as “others” (23%) since their pattern was highly variable. Age was a significant predictor of eating pattern, with older pre-school children more likely to be non-eaters. Plate-clearers had higher enjoyment of food and lower satiety responsiveness than non-eaters who scored highest on food fussiness. Children in the added energy condition showed the smallest change in intake over time, compared to those in the basic or sweetened artichoke condition. Clearly whilst repeated exposure familiarises children with a novel food, alternative strategies that focus on encouraging initial tastes of the target food might be needed for the fussier and older pre-school children.     

Genetic variability in residual feed intake in rainbow trout clones and testing of indirect selection criteria (Open Access publication)

Little is known about the genetic basis of residual feed intake (RFI) variation in fish, since this trait is highly sensitive to environmental influences, and feed intake of individuals is difficult to measure accurately. The purpose of this work was (i) to assess the genetic variability of RFI estimated by an X-ray technique and (ii) to develop predictive criteria for RFI. Two predictive criteria were tested: loss of body weight during feed deprivation and compensatory growth during re-feeding. Ten heterozygous rainbow trout clones were used. Individual intake and body weight were measured three times at threeweek intervals. Then, individual body weight was recorded after two cycles of a three-week feed deprivation followed by a three-week re-feeding. The ratio of the genetic variance to the phenotypic variance was found high to moderate for growth, feed intake, and RFI (VG/VP = 0.63 ± 0.11, 0.29 ± 0.11, 0.29 ± 0.09, respectively). The index that integrates performances achieved during deprivation and re-feeding periods explained 59% of RFI variations. These results provide a basis for further studies on the origin of RFI differences and show that indirect criteria are good candidates for future selective breeding programs.     

Effective lipid lowering diets including lean meat

The plasma lipid and lipoprotein responses to two modified isoenergetic diets including meat were studied in 15 free living men with hyperlipidaemia (mean plasma cholesterol and triglyceride concentrations 8·1 and 3·4 mmol/l). A reference diet (diet A, 42% energy from fat, ratio of polyunsaturated to saturated fatty acids (P:S ratio) 0·2) was compared with a fat reduced diet (diet B, 35% energy from fat, P:S ratio 0·5) and with a further fat modified diet supplemented with fibre (diet C, 27% energy from fat, P:S ratio 1·0). Daily intake of meat and meat products (180 g/day) was the same in each dietary period; that in diet A had a fat content typical of the average British diet, whereas that in diets B and C was based on very lean meat and meat products. During consumption of diet B the plasma cholesterol concentration fell by 8·6% and low density lipoprotein cholesterol by 11%. During consumption of diet C plasma cholesterol fell by 18·5% and low density lipoprotein cholesterol by 23·8%. Triglyceride and high density lipoprotein cholesterol concentrations and body weight did not change appreciably during the study.A modified diet including a moderate amount of lean meat and meat products is compatible with a reduced lipoprotein mediated risk of atherosclerotic heart disease.     

Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates – A Substudy

Background

Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates.

Objective

To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake.

Methods

A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m², age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-²H₅]phenylalanine and L-[ring-²H₂]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans.

Results

After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0.045±0.01%/h;P = 0.620).

Conclusions

In the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and does not lower basal muscle protein synthesis rates when compared to a high-protein intake.

Trial Registration

Clinicaltrials.gov NCT01551238.     

Infantile Overnutrition in the First Year of Life: A Field Study in Dudley,Worcestershire

A survey of feeding patterns and nutrient intake in relation to the growth of 300 normal infants up to 1 year of age in Dudley, Worcestershire, highlights a problem of overnutrition in the group; 50 (16·7%) were found to be suffering from infantile obesity and a further 83 (27·7%) were overweight.During the first three months of life the daily energy intakes of 136 cal/kg body weight for boys and 149 for girls were markedly greater than the level of 120/kg recommended by the Department of Health and Social Security. This coincided with the early addition of solid foods to a full milk intake. 119 babies (39·7%) were offered solids before they were 4 weeks old and 280 (93·3%) before 13 weeks of age. Some babies had solids from the first week after birth. Protein intake was persistently high throughout the first year, and the mean intake of 32·7 g/day was much greater than the intake of 20 g for infants aged up to 1 year recommended by the Department of Health. Standards for fat and carbohydrate intake are not available but in comparison with the levels reported in breast-fed babies intake of fat and carbohydrate was high in the first three months and came closer to the desired level for the former and remained slightly high for the latter in the subsequent age quarters.The relation of childhood and subsequent adult obesity to infant feeding patterns is not yet clear, but there is a high correlation between obese parents and obese and overweight babies; had these babies not been overfed the condition might have been prevented.     

Metabolic and Behavioral Compensations in Response to Caloric Restriction: Implications for the Maintenance of Weight Loss

Background

Metabolic and behavioral adaptations to caloric restriction (CR) in free-living conditions have not yet been objectively measured.

Methodology and Principal Findings

Forty-eight (36.8±1.0 y), overweight (BMI 27.8±0.7 kg/m²) participants were randomized to four groups for 6-months; Control: energy intake at 100% of energy requirements; CR: 25% calorie restriction; CR+EX: 12.5% CR plus 12.5% increase in energy expenditure by structured exercise; LCD: low calorie diet (890 kcal/d) until 15% weight reduction followed by weight maintenance. Body composition (DXA) and total daily energy expenditure (TDEE) over 14-days by doubly labeled water (DLW) and activity related energy activity (AREE) were measured after 3 (M3) and 6 (M6) months of intervention. Weight changes at M6 were −1.0±1.1% (Control), −10.4±0.9% (CR), −10.0±0.8% (CR+EX) and −13.9±0.8% (LCD). At M3, absolute TDEE was significantly reduced in CR (−454±76 kcal/d) and LCD (−633±66 kcal/d) but not in CR+EX or controls. At M6 the reduction in TDEE remained lower than baseline in CR (−316±118 kcal/d) and LCD (−389±124 kcal/d) but reached significance only when CR and LCD were combined (−351±83 kcal/d). In response to caloric restriction (CR/LCD combined), TDEE adjusted for body composition, was significantly lower by −431±51 and −240±83 kcal/d at M3 and M6, respectively, indicating a metabolic adaptation. Likewise, physical activity (TDEE adjusted for sleeping metabolic rate) was significantly reduced from baseline at both time points. For control and CR+EX, adjusted TDEE (body composition or sleeping metabolic rate) was not changed at either M3 or M6.

Conclusions

For the first time we show that in free-living conditions, CR results in a metabolic adaptation and a behavioral adaptation with decreased physical activity levels. These data also suggest potential mechanisms by which CR causes large inter-individual variability in the rates of weight loss and how exercise may influence weight loss and weight loss maintenance.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00099151","term_id":"NCT00099151"}}NCT00099151     

Compensatory Growth in Juveniles of Freshwater Redclaw Crayfish Cherax quadricarinatus Reared at Three Different Temperatures: Hyperphagia and Food Efficiency as Primary Mechanisms

Feeding restriction, as a trigger for compensatory growth, might be considered an alternative viable strategy for minimizing waste as well as production costs. The study assessed whether juvenile redclaw crayfish Cherax quadricarinatus (initial weight 0.99 ±0.03 g) was able to compensate for feeding restriction at different temperatures (23±1, 27±1 and 31±1°C). Hyperphagia, food utilization efficiency, energetic reserves, and hepatopancreas structure were analyzed. Three temperatures and two feeding regimes (DF-daily fed throughout the experiment and CF- 4 days food deprivation followed by 4 days of feeding, intermittently) were tested. The restriction period was from day 1 to 45, and the recovery period was from day 45 to 90. The previously restricted crayfish held at 23, 27, and 31 ± 1°C displayed complete body weight catch-up through compensatory growth following the restriction period with depressed growth. The mechanisms that might explain this response were higher feed intake (hyperphagia), and increased food utilization efficiency. Hepatopancreatic lipids were used as a metabolic fuel and hepatosomatic index was reduced in the previously restricted crayfish, but recovery at the same level of unrestricted crayfish occurred after the shift to daily feeding. The highest temperature affected adversely growth, feed intake, food efficiency, and metabolism of crayfish, whereas the lowest temperature and feeding restriction induced a more efficient growth of the crayfish.     

Binge Drinking and Blood Pressure: Cross-Sectional Results of the HAPIEE Study

Objectives

To investigate whether binge drinking pattern influences blood pressure independently from drinking volume or whether it modifies the effect of volume of drinking.

Methods

We used cross-sectional data from population samples of 7559 men and 7471 women aged 45–69 years in 2002-05, not on antihypertensive medication, from Russia, Poland and Czech Republic. Annual alcohol intake, drinking frequency and binge drinking (≥100 g in men and ≥60 g in women in one session at least once a month) were estimated from graduated frequency questionnaire. Blood pressure was analysed as continuous variables (systolic and diastolic pressure) and a binary outcome (≥140/90 mm Hg).

Results

In men, annual alcohol intake and drinking frequency were strongly associated with blood pressure. The odds ratio of high blood pressure for binge drinking in men was 1.62 (95% CI 1.45–1.82) after controlling for age, country, body mass index, education and smoking; additional adjustment for annual alcohol intake reduced it to 1.20 (1.03–1.39). In women, the fully adjusted odds ratio of high blood pressure for binge drinking was 1.31 (1.05–1.63). Binge drinking did not modify the effect of annual alcohol intake. Consuming alcohol as wine, beer or spirits had similar effects.

Conclusions

The results suggest that the independent long-term effect of binge drinking was modest, that binge drinking did not modify the effect of alcohol intake, and that different alcoholic beverages had similar effects on blood pressure.     

Quantification of Abdominal Fat Depots in Rats and Mice during Obesity and Weight Loss Interventions

Background & Aims

Obesity is a leading healthcare issue contributing to metabolic diseases. There is a great interest in non-invasive approaches for quantitating abdominal fat in obese animals and humans. In this work, we propose an automated method to distinguish and quantify subcutaneous and visceral adipose tissues (SAT and VAT) in rodents during obesity and weight loss interventions. We have also investigated the influence of different magnetic resonance sequences and sources of variability in quantification of fat depots.

Materials and Methods

High-fat diet fed rodents were utilized for investigating the changes during obesity, exercise, and calorie restriction interventions (N = 7/cohort). Imaging was performed on a 7T Bruker ClinScan scanner using fast spin echo (FSE) and Dixon imaging methods to estimate the fat depots. Finally, we quantified the SAT and VAT volumes between the L1–L5 lumbar vertebrae using the proposed automatic hybrid geodesic region-based curve evolution algorithm.

Results

Significant changes in SAT and VAT volumes (p<0.01) were observed between the pre- and post-intervention measurements. The SAT and VAT were 44.22±9%, 21.06±1.35% for control, −17.33±3.07%, −15.09±1.11% for exercise, and 18.56±2.05%, −3.9±0.96% for calorie restriction cohorts, respectively. The fat quantification correlation between FSE (with and without water suppression) sequences and Dixon for SAT and VAT were 0.9709, 0.9803 and 0.9955, 0.9840 respectively. The algorithm significantly reduced the computation time from 100 sec/slice to 25 sec/slice. The pre-processing, data-derived contour placement and avoidance of strong background–image boundary improved the convergence accuracy of the proposed algorithm.

Conclusions

We developed a fully automatic segmentation algorithm to quantitate SAT and VAT from abdominal images of rodents, which can support large cohort studies. We additionally identified the influence of non-algorithmic variables including cradle disturbance, animal positioning, and MR sequence on the fat quantification. There were no large variations between FSE and Dixon-based estimation of SAT and VAT.     

Effects of dietary macronutrients on the hepatic transcriptome and serum metabolome in mice

Dietary macronutrient composition influences both hepatic function and aging. Previous work suggested that longevity and hepatic gene expression levels were highly responsive to dietary protein, but almost unaffected by other macronutrients. In contrast, we found expression of 4005, 4232, and 4292 genes in the livers of mice were significantly associated with changes in dietary protein (5%–30%), fat (20%–60%), and carbohydrate (10%–75%), respectively. More genes in aging‐related pathways (notably mTOR, IGF‐1, and NF‐kappaB) had significant correlations with dietary fat intake than protein and carbohydrate intake, and the pattern of gene expression changes in relation to dietary fat intake was in the opposite direction to the effect of graded levels of caloric restriction consistent with dietary fat having a negative impact on aging. We found 732, 808, and 995 serum metabolites were significantly correlated with dietary protein (5%–30%), fat (8.3%–80%), and carbohydrate (10%–80%) contents, respectively. Metabolomics pathway analysis revealed sphingosine‐1‐phosphate signaling was the significantly affected pathway by dietary fat content which has also been identified as significant changed metabolic pathway in the previous caloric restriction study. Our results suggest dietary fat has major impact on aging‐related gene and metabolic pathways compared with other macronutrients.     

Propranolol,a β-adrenergic antagonist,attenuates the decrease in trabecular bone mass in high calorie diet fed growing mice

We investigated the effects of high calorie and low calorie diets on skeletal integrity, and whether β-adrenergic blockade (BB) attenuates bone loss induced by dietary calorie alteration. Male 6-week-old C57BL/6 mice were assigned to either an ad-lib fed control diet (CON), a high calorie diet (HIGH), or a low calorie diet (LOW) group. In each diet group, mice were treated with either vehicle (VEH) or propranolol, a β-adrenergic antagonist. Over 12-weeks, β-blockade mitigated body weight and fat mass increases induced by the high calorie diet. Femoral trabecular bone mineral density and the expression levels of osteogenic marker genes in bone marrow cells were reduced in HIGHVEH and LOWVEH mice, and BB significantly attenuated this decline only in HIGH mice. In summary, the magnitude of bone loss induced by low calorie diet was greater than that caused by high calorie diet in growing mice, and β-blockade mitigated high calorie diet-induced bone loss. [BMB Reports 2014; 47(9): 506-511]     

Alterations of Neuromuscular Function after the World's Most Challenging Mountain Ultra-Marathon

We investigated the physiological consequences of the most challenging mountain ultra-marathon (MUM) in the world: a 330-km trail run with 24000 m of positive and negative elevation change. Neuromuscular fatigue (NMF) was assessed before (Pre-), during (Mid-) and after (Post-) the MUM in experienced ultra-marathon runners (n = 15; finish time  = 122.43 hours ±17.21 hours) and in Pre- and Post- in a control group with a similar level of sleep deprivation (n = 8). Blood markers of muscle inflammation and damage were analyzed at Pre- and Post-. Mean ± SD maximal voluntary contraction force declined significantly at Mid- (−13±17% and −10±16%, P<0.05 for knee extensor, KE, and plantar flexor muscles, PF, respectively), and further decreased at Post- (−24±13% and −26±19%, P<0.01) with alteration of the central activation ratio (−24±24% and −28±34% between Pre- and Post-, P<0.05) in runners whereas these parameters did not change in the control group. Peripheral NMF markers such as 100 Hz doublet (KE: −18±18% and PF: −20±15%, P<0.01) and peak twitch (KE: −33±12%, P<0.001 and PF: −19±14%, P<0.01) were also altered in runners but not in controls. Post-MUM blood concentrations of creatine kinase (3719±3045 Ul·¹), lactate dehydrogenase (1145±511 UI·L⁻¹), C-Reactive Protein (13.1±7.5 mg·L⁻¹) and myoglobin (449.3±338.2 µg·L⁻¹) were higher (P<0.001) than at Pre- in runners but not in controls. Our findings revealed less neuromuscular fatigue, muscle damage and inflammation than in shorter MUMs. In conclusion, paradoxically, such extreme exercise seems to induce a relative muscle preservation process due likely to a protective anticipatory pacing strategy during the first half of MUM and sleep deprivation in the second half.