Neurally-mediated increase in calcineurin activity regulates cardiac contractile function in absence of hypertrophy

Objective: The calcineurin pathway has been involved in the development of cardiac hypertrophy, yet it remains unknown whether calcineurin activity can be regulated in myocardium independently from hypertrophy and cardiac load. Methods: To test that hypothesis, we measured calcineurin activity in a rat model of infrarenal aortic constriction (IR), which affects neurohormonal pathways without increasing cardiac afterload. Results: In this model, there was no change in arterial pressure over the 4-week experimental period, and the left ventricle/body weight ratio did not increase. At 2 weeks after IR, calcineurin activity was increased 1.8-fold (P

Longitudinal relationships among overweight, life satisfaction, and aspirations in young women

Objective: This study investigated associations of overweight status and changes in overweight status over time with life satisfaction and future aspirations among a community sample of young women. Research Methods and Procedures: A total of 7865 young women, initially 18 to 23 years of age, completed two surveys that were 4 years apart. These women provided data on their future life aspirations in the areas of further education, work/career, marital status, and children, as well as their satisfaction with achievements to date in a number of life domains. Women reported their height and weight and their sociodemographic characteristics, including current socioeconomic status (occupation). Results: Young women's aspirations were cross-sectionally related to BMI category, such that obese women were less likely to aspire to further education, although this relationship seemed explained largely by current occupation. Even after adjusting for current occupation, young women who were obese were more dissatisfied with work/career/study, family relationships, partner relationships, and social activities. Weight status was also longitudinally associated with aspirations and life satisfaction. Women who were overweight or obese at both surveys were more likely than other women to aspire to other types of employment (including self-employed and unpaid work in the home) as opposed to full-time employment. They were also less likely to be satisfied with study or partner relationships. Women who resolved their overweight/obesity status were more likely to aspire to being childless than other women. Discussion: These results suggest that being overweight/obese may have a lasting effect on young women's life satisfaction and their future life aspirations.

Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life

Background and aim: Obesity is a risk factor for progression of fibrosis in chronic liver diseases such as non-alcoholic fatty liver disease and hepatitis C. The aim of this study was to investigate the longer term effect of weight loss on liver biochemistry, serum insulin levels, and quality of life in overweight patients with liver disease and the effect of subsequent weight maintenance or regain. Patients: Thirty one patients completed a 15 month diet and exercise intervention. Results: On completion of the intervention, 21 patients (68%) had achieved and maintained weight loss with a mean reduction of 9.4 (4.0)% body weight. Improvements in serum alanine aminotransferase (ALT) levels were correlated with the amount of weight loss (r=0.35, p=0.04). In patients who maintained weight loss, mean ALT levels at 15 months remained significantly lower than values at enrolment (p=0.004), while in regainers (n=10), mean ALT levels at 15 months were no different to values at enrolment (p=0.79). Improvements in fasting serum insulin levels were also correlated with weight loss (r=0.46, p=0.04), and subsequent weight maintenance sustained this improvement. Quality of life was significantly improved after weight loss. Weight maintainers sustained recommended levels of physical activity and had higher fasting insulin levels (p=0.03) at enrolment than weight regainers. Conclusion: In summary, these findings demonstrate that maintenance of weight loss and exercise in overweight patients with liver disease results in a sustained improvement in liver enzymes, serum insulin levels, and quality of life. Treatment of overweight patients should form an important component of the management of those with chronic liver disease.

Feeding strategies for grain-fed cattle in a hot environment

Six Bos taurus (Hereford) steers (body weight 324 22 kg) were used in a 45-day study with a replicated 3 x 3 Latin-square design. Three treatments [ad libitum feeding (ADLIB); limit feeding, 85% of ad libitum (LIMIT); bunk management feeding where steers were only given access to feed from 1600 to 0800 hours the following day (BUNK)] were imposed over 3 periods, with 2 steers assigned to each treatment in each period. Cattle were managed in a temperature-controlled metabolism unit and were exposed to both thermoneutral (17.7degreesC-26.1degreesC) and hot (16.7degreesC-32.9degreesC) environmental conditions. By design, during the thermoneutral period, the ADLIB cattle displayed greater intake (P < 0.05) than the LIMIT group, with the BUNK group being intermediate. However, during the hot period, both the LIMIT and BUNK treatment groups increased feed intake 4-5%, whereas feed intake of the ADLIB treatment group declined nearly 2%. During both periods respiration rate (RR, breath/min) followed the same pattern that was observed for feed intake, with the greatest (P < 0.05) RR found in the ADLIB treatment group (81.09 and 109.55, thermoneutral and hot, respectively) and lowest (P < 0.05) RR in the LIMIT treatment group (74.47 and 102.76, thermoneutral and hot, respectively). Rectal temperature (RT) did not differ among treatments during the thermoneutral period or the first hot day, although during the thermoneutral period the ADLIB treatment group did tend to display a lower RT, possibly as a result of other physiological processes (pulse rate and RR) aiding to keep RT lower. During the hot period, differences in RT were found on Day 5, with the LIMIT cattle having lower (P < 0.10) RT (38.92degreesC) than the ADLIB (39.18degreesC) cattle, with BUNK cattle RT (39.14degreesC) being intermediate. However, when hourly data were examined, the ADLIB cattle had greater(P < 0.05) RT than the BUNK and LIMIT at 1800 hours and greater RT (P < 0.05) than the LIMIT group at 1400, 1500, and 1600 hours. Clearly, a change in diurnal RT pattern was obtained by using the LIMIT and BUNK feeding regimen. Both of these groups displayed a peak RT during the hot conditions, between 2100 and 2200 hours, whereas the ADLIB group displayed a peak RT between 1400 and 1500 hours, a time very close to when peak climatic stress occurs. Based on these results it is apparent that feedlot managers could alleviate the effects of adverse hot weather on cattle by utilising either a limit-feeding regimen or altering bunk management practices to prevent feed from being consumed several hours prior to the hottest portion of the day.

Caffeine, cognition, and persuasion: Evidence for caffeine increasing the systematic processing of persuasive messages

Caffeine is known to increase arousal, attention, and information processing-all factors implicated in facilitating persuasion. In a standard attitude-change paradigm, participants consumed an orange-juice drink that either contained caffeine (3.5 mg/kg body weight) or did not (placebo) prior to reading a counterattitudinal communication (anti-voluntary euthanasia). Participants then completed a thought-listing task and a number of attitude scales. The first experiment showed that those who consumed caffeine showed greater agreement with the communication (direct attitude: voluntary euthanasia) and on an issue related to, but not contained in, the communication (indirect attitude: abortion). The order in which direct and indirect attitudes were measured did not affect the results. A second experiment manipulated the quality of the arguments in the message (strong vs. weak) to determine whether systematic processing had occurred. There was evidence that systematic processing occurred in both drink conditions, but was greater for those who had consumed caffeine. In both experiments, the amount of message-congruent thinking mediated persuasion. These results show that caffeine can increase the extent to which people systematically process and are influenced by a persuasive communication.

The effects of caffeine consumption on direct and indirect majority and minority influence

A study is reported that examines the effect of caffeine consumption on majority and minority influence. In a double blind procedure, 72 participants consumed an orange drink, which either contained caffeine (3.5mg per kilogram of body weight) or did not (placebo). After a 40-minute delay, participants read a counter-attitudinal message (antivoluntary euthanasia) endorsed by either a numerical majority or minority. Both direct (message issue, i.e., voluntary euthanasia) and indirect (message issue-related, i.e., abortion) change was assessed by attitude scales completed before and after exposure to the message. In the placebo condition, the findings replicated the predictions of Moscovici's (1980) conversion theory; namely, majorities leading to compliance (direct influence) and minorities leading to conversion (indirect influence). When participants had consumed caffeine, majorities not only led to more direct influence than in the placebo condition but also to indirect influence. Minorities, by contrast, had no impact on either level of influence. The results suggest that moderate levels of caffeine increase systematic processing of the message but the consequences of this vary for each source. When the source is a majority there was increased indirect influence while for a minority there was decreased indirect influence. The results show the need to understand how contextual factors can affect social influence processes.

Weight gained in two years by a population of mid-aged women: how much is too much?

Objective: To establish the prevalence of weight change in mid-aged women over a 2-year period, and to assess the relationship between weight change and physical and mental well-being (SF36) in order to begin debate about the need for quantified standards of weight gain. Design: Prospective study of weight change and well-being over a 2-year period among mid-aged women participating in a large national survey. Subjects: Seven thousand two hundred and seventy women without surgical menopause aged between 45 and 50 years (termed mid-aged), enrolled in the Australian Longitudinal Study on Women's Health. Measurements: Weight change (self-reported weight at two time points) and physical and mental well-being (SF-36) explored using linear regression, while adjusting for potential confounders. Results: Only half the women maintained their weight within 2.25 kg, and one-third gained more than this amount in a 2-year period. While weight gain (>= 2.25 kg) was negatively associated with physical well-being, both weight loss and weight gain were associated with poorer mental well-being. Conclusion: This is the first prospective study using a large, population-based cohort to demonstrate that small changes in weight are associated with changes in well-being in mid-aged Australian women. It provides further evidence of the need for public health messages to specify the actual amount that constitutes weight gain, but further research is needed to establish these standards for the entire population.

Whose socioeconomic status influences a woman's obesity risk: her mother's, her father's, or her own?

Background Evidence on the relative influence of childhood vs adulthood socioeconomic conditions on obesity risk is limited and equivocal. The objective of this study was to investigate associations of several indicators of mothers', fathers', and own socioeconomic status, and intergenerational social mobility, with body mass index (BMI) and weight change in young women. Methods This population-based cohort study used survey data provided by 8756 women in the young cohort (aged 18-23 years at baseline) of the Australian Longitudinal Study on Women's Health. In 1996 and 2000, women completed mailed surveys in which they reported their height and weight, and their own, mother's, and father's education and occupation. Results Multiple linear regression models showed that both childhood and adulthood socioeconomic status were associated with women's BMI and weight change, generally in the hypothesized (inverse) direction, but the associations varied according to socioeconomic status and weight indicator. Social mobility was associated with BMI (based on father's socioeconomic status) and weight change (based on mother's socioeconomic status), but results were slightly less consistent. Conclusions Results suggest lasting effects of childhood socioeconomic status on young women's weight status, independent of adult socioeconomic status, although the effect may be attenuated among those who are upwardly socially mobile. While the mechanisms underlying these associations require further investigation, public health strategies aimed at preventing obesity may need to target families of low socioeconomic status early in children's lives.

Caffeine, cognition, and persuasion:evidence for caffeine increasing the systematic processing of persuasive messages

Caffeine is known to increase arousal, attention, and information processing–all factors implicated in facilitating persuasion. In a standard attitude-change paradigm, participants consumed an orange-juice drink that either contained caffeine (3.5 mg/kg body weight) or did not (placebo) prior to reading a counterattitudinal communication (anti-voluntary euthanasia). Participants then completed a thought-listing task and a number of attitude scales. The first experiment showed that those who consumed caffeine showed greater agreement with the communication (direct attitude: voluntary euthanasia) and on an issue related to, but not contained in, the communication (indirect attitude: abortion). The order in which direct and indirect attitudes were measured did not affect the results. A second experiment manipulated the quality of the arguments in the message (strong vs. weak) to determine whether systematic processing had occurred. There was evidence that systematic processing occurred in both drink conditions, but was greater for those who had consumed caffeine. In both experiments, the amount of message-congruent thinking mediated persuasion. These results show that caffeine can increase the extent to which people systematically process and arc influenced by a persuasive communication.

The effects of caffeine consumption on direct and indirect majority and minority influence

A study is reported that examines the effect of caffeine consumption on majority and minority influence. In a double blind procedure, 72 participants consumed an orange drink, which either contained caffeine (3.5mg per kilogram of body weight) or did not (placebo). After a 40-minute delay, participants read a counter-attitudinal message (antivoluntary euthanasia) endorsed by either a numerical majority or minority. Both direct (message issue, i.e., voluntary euthanasia) and indirect (message issue-related, i.e., abortion) change was assessed by attitude scales completed before and after exposure to the message. In the placebo condition, the findings replicated the predictions of Moscovici's (1980) conversion theory; namely, majorities leading to compliance (direct influence) and minorities leading to conversion (indirect influence). When participants had consumed caffeine, majorities not only led to more direct influence than in the placebo condition but also to indirect influence. Minorities, by contrast, had no impact on either level of influence. The results suggest that moderate levels of caffeine increase systematic processing of the message but the consequences of this vary for each source. When the source is a majority there was increased indirect influence while for a minority there was decreased indirect influence. The results show the need to understand how contextual factors can affect social influence processes.

Studies on the antiobesity effect of zinc-α2-glycoprotein in the ob/ob mouse

OBJECTIVE: To investigate the mechanism of the lipid depletion by zinc-a(2)-glycoprotein (ZAG). DESIGN: Studies were conducted in the ob/ob mouse, or on isolated adipocytes from these animals or their lean counterparts. RESULTS: Treatment of these animals for 15 days with ZAG (100? µg, intravenously, daily) resulted in a reduction of body weight of 6.55? g compared with phosphate-buffered saline-treated controls, without a change in food or water intake, but with a 0.4?°C rise in rectal temperature. ZAG-treated mice had a 30% reduction in carcass fat mass and a twofold increase in weight of brown adipose tissue. Epididymal adipocytes from ZAG-treated mice showed an increased expression of ZAG and hormone-sensitive lipase (HSL), and this was maintained for a further 3 days in the absence of ZAG. There was an increased lipolytic response to isoproterenol, which was retained for 3 days in vitro in the absence of ZAG. Expression of HSL was also increased in subcutaneous and visceral adipose tissue, as was also adipose triglyceride lipase (ATGL). There was a rapid loss of labelled lipid from epididymal adipose tissue of ZAG-treated mice, but not from the other depots, reflecting the difference in sensitivity to lipolytic stimuli. The increased expression of HSL and ATGL may involve the extracellular signal-regulated kinase (ERK) pathway, as the active (phospho) form was upregulated in all adipose depots after ZAG administration, whereas in vitro studies showed induction of HSL and ATGL by ZAG to be attenuated by PD98059, an inhibitor of the ERK pathway. CONCLUSION: These results suggest that ZAG not only induces direct lipolysis, but also sensitizes adipose tissue to other lipolytic stimuli.

Dapagliflozin monotherapy in drug-naïve patients with diabetes:a randomized-controlled trial of low-dose range

Aims: Many patients with type 2 diabetes are suboptimally managed with currently available therapies. Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, has shown efficacy in reducing diabetic hyperglycaemia. This study assessed efficacy of three lower doses in recently diagnosed patients. Methods: This phase 3, randomized, double-blind, placebo-controlled study assigned treatment-naïve patients to placebo or dapagliflozin monotherapy (1, 2.5 or 5 mg) daily for 24 weeks. Patients were antidiabetic drug-naïve with inadequate glycaemic control [haemoglobin A1c (HbA1c) =7.0 and =10.0%]. The primary efficacy endpoint was change in HbA1c from baseline. Secondary endpoints included changes in body weight and fasting plasma glucose (FPG), and proportions achieving HbA1c

Editorial : which weight loss diet?

Full editorial: A recent study evaluating the long-term (2 yr) weight reducing efficacy of different types of diets – high or low in carbohydrates (CHOs), protein or fat - confirmed that it is calorie deficit not dietary composition that determines the loss and maintenance of body weight.1 Is there any advantage in following a specific weight loss diet? Short-term use of nutritionally complete commercially available (very) low calorie diets has benefited people with diabetes when  supported by education programmes.2 Initial weight loss has been encouraging with some fad diets eg the Atkins and the South Beach diets, but these diets are difficult to maintain and there are safety issues regarding their short- and long-term use – especially in people with diabetes.3 The types of macronutrients consumed can have a considerable impact on glycaemic control and energy metabolism. Although a low CHO diet additionally enhances initial weight loss by reducing cellular water content, if fat is not proportionally reduced the diet may not benefit the lipid profile for vascular disease risk. High fat and high protein diets – which are simultaneously low in CHOs – increase vulnerability to hypoglycaemia in people taking insulin secretagogues or on insulin therapy, and may promote excess fat metabolism and ketogenesis, particularly in people vulnerable to lack of insulin. Very low protein diets are not recommended as lean body mass tends to be reduced in diabetes. Altering the macronutrient balance has implications for the micronutrient mix: deficiencies are higher if more foods are excluded and conversely specific micronutrient excess can occur with some fad diets. The altered nutrient mix affects intestinal fauna and flora, and gut motility and glycaemic control are influenced by the quantity and type of fibre consumed. Support programmes help individuals achieve long term weight loss and there is mounting evidence that community schemes which educate and promote lifestyle changes may stem the rising tide of obesity and consequent type 2 diabetes.4 Consuming smaller portions of a balanced diet (and adjusting antidiabetic medications accordingly) will create an energy deficit to promote healthy weight loss. Increased movement/exercise will enhance this energy deficit. Knowledge (eg 1g fat has 2.25 times more energy than 1g CHO) allows sensible food choices and compensation for inclusion of small volumes of  ‘naughty but nice’ foods. Ultimately weight control requires self control. References 1. Sacks FM, Bray GA, Carey VJ et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009;360:859–73. 2. Bennett P. Obesity, diabetes and VLCD. Br J Diabetes Vasc Dis 2004;4:328–30. 3. Baldwin EJ. Fad diets in diabetes. Br J Diabetes Vasc DIs 2004;4:333–7. 4. Romon M, Lommoz A, Tafflet M et al. Downward trends in the prevalence of childhood overweight in the setting of 12-year school- and community-based programmes. Public Health Nutr 2008; Dec 28, 1–8 [Epub ahead of print].

Induction of lipolysis in vitro and loss of body fat in vivo by zinc-alpha(2)-glycoprotein

Loss of adipose tissue in cancer cachexia has been associated with tumour production of a lipid-mobilizing factor (LMF) which has been shown to be homologous with the plasma protein zinc-a2-glycoprotein (ZAG). The aim of this study was to compare the ability of human ZAG with LMF to stimulate lipolysis in vitro and induce loss of body fat in vivo, and to determine the mechanisms involved. ZAG was purified from human plasma using a combination of Q Sepharose and Superdex 75 chromatography, and was shown to stimulate glycerol release from isolated murine epididymal adipocytes in a dose-dependent manner. The effect was enhanced by the cyclic AMP phosphodiesterase inhibitor Ro20-1724, and attenuated by freeze/thawing and the specific ß3-adrenoreceptor antagonist SR59230A. In vivo ZAG caused highly significant, time-dependent, decreases in body weight without a reduction in food and water intake. Body composition analysis showed that loss of body weight could be attributed entirely to the loss of body fat. Loss of adipose tissue may have been due to the lipolytic effect of ZAG coupled with an increase in energy expenditure, since there was a dose-dependent increase in expression of uncoupling protein-1 (UCP-1) in brown adipose tissue. These results suggest that ZAG may be effective in the treatment of obesity.