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Saturated fatty acid (SFA) vs polyunsaturated fatty acid (PUFA) may promote nonalcoholic fatty liver disease by yet unclear mechanisms. To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans. Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction. General community. Men and women who are overweight or have obesity (n = 61). Muffins, high in either palm (SFA) or sunflower oil (PUFA), were added to the habitual diet. Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots. By design, body weight gain was similar in SFA (2.31 ± 1.38 kg) and PUFA (2.01 ± 1.90 kg) groups, P = 0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat, or total body fat compared with PUFA. SFA consistently increased, whereas PUFA reduced circulating ceramides, changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction. SFA markedly induces liver fat and serum ceramides, whereas dietary PUFA prevents liver fat accumulation and reduces ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.

Abstract Background The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH). Methods We conducted a UK multicenter phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017. Serum markers of glucose homeostasis, lipid metabolism, renal and hepatic function, inflammation and androgen profiles were determined and examined in relation to changes in fat and lean mass by dual-energy X-ray absorptiometry. Results Patients receiving AZD4017 showed significant improvements in lipid profiles (decreased cholesterol, increased high-density lipoprotein [HDL] and cholesterol/HDL ratio), markers of hepatic function (decreased alkaline phosphatase and gamma-glutamyl transferase), and increased lean muscle mass (1.8%, P < .001). No changes in body mass index, fat mass, and markers of glucose metabolism or inflammation were observed. Patients receiving AZD4017 demonstrated increased levels of circulating androgens, positively correlated with changes in total lean muscle mass. Conclusions These beneficial metabolic changes represent a reduction in risk factors associated with raised intracranial pressure and represent further beneficial therapeutic outcomes of 11β-HSD1 inhibition by AZD4017 in this overweight IIH cohort. In particular, beneficial changes in lean muscle mass associated with AZD4017 may reflect new applications for this nature of inhibitor in the management of conditions such as sarcopenia.

As the prevalence of overweight and obesity have risen over the past few decades, so have weight control attempts. Research has shown, however, that intentional weight loss results are often short-lived, with people regaining the weight over time. This can lead to weight cycling-losing and gaining weight repeatedly. Previous research, mostly done over two decades ago, concluded there was no relationship between weight cycling and psychological health. The goal of the current paper was to re-examine the relationship between weight cycling and depressive symptoms in a national sample of American adults (N = 2702; 50.7% female; mean age = 44.8 years). If, as hypothesized, there is a relationship between more frequent weight cycling and depressive symptoms, then internalized weight stigma will be examined as a potential mediator of the relationship. Results of a cross-sectional survey showed that 74.6% of adults report they have intentionally tried to lose weight. Amongst those who have tried to lose to weight, the average number of weight cycles over the lifetime was 7.82 cycles. Simultaneous regression showed that greater weight cycling was related to greater reported depressive symptoms (β = .15, p < .001), controlling for age, gender, education, income, and body mass index. Internalized weight stigma was a partial mediator of this relationship. Discussion focuses on the potential implications for weight cycling and mental health.

The idea of body weight regulation implies that a biological mechanism exerts control over energy expenditure and food intake. This is a central tenet of energy homeostasis. However, the source and identity of the controlling mechanism have not been identified, although it is often presumed to be some long-acting signal related to body fat, such as leptin. Using a comprehensive experimental platform, we have investigated the relationship between biological and behavioural variables in two separate studies over a 12-week intervention period in obese adults (total n 92). All variables have been measured objectively and with a similar degree of scientific control and precision, including anthropometric factors, body composition, RMR and accumulative energy consumed at individual meals across the whole day. Results showed that meal size and daily energy intake (EI) were significantly correlated with fat-free mass (FFM, P values < 0·02–0·05) but not with fat mass (FM) or BMI (P values 0·11–0·45) (study 1, n 58). In study 2 (n 34), FFM (but not FM or BMI) predicted meal size and daily EI under two distinct dietary conditions (high-fat and low-fat). These data appear to indicate that, under these circumstances, some signal associated with lean mass (but not FM) exerts a determining effect over self-selected food consumption. This signal may be postulated to interact with a separate class of signals generated by FM. This finding may have implications for investigations of the molecular control of food intake and body weight and for the management of obesity.

There is increasing evidence that obesity is related to asthma development and severity. However, it is largely unknown whether weight reduction can influence asthma management, especially in children. To determine the effects of a multifactorial weight reduction intervention on asthma management in overweight/obese children with (a high risk of developing) asthma. An 18-month weight-reduction randomized controlled trial was conducted in 87 children with overweight/obesity and asthma. Every six months, measurements of anthropometry, lung function, lifestyle parameters and inflammatory markers were assessed. Analyses were performed with linear mixed models for longitudinal analyses. After 18 months, the body mass index-standard deviation score decreased by -0.14±0.29 points (p<0.01) in the intervention group and -0.12±0.34 points (p<0.01) in the control group. This change over time did not differ between groups (p>0.05). Asthma features (including asthma control and asthma-related quality of life) and lung function indices (static and dynamic) improved significantly over time in both groups. The FVC% predicted improved over time by 10.1 ± 8.7% in the intervention group (p<0.001), which was significantly greater than the 6.1 ± 8.4% in the control group (p<0.05). Clinically relevant improvements in body weight, lung function and asthma features were found in both the intervention and control group, although some effects were more pronounced in the intervention group (FVC, asthma control, and quality of life). This implies that a weight reduction intervention could be clinically beneficial for children with asthma. ClinicalTrials.gov NCT00998413.

Objective: To determine the effects of a 15-week high-intensity intermittent exercise (HIIE) program on subcutaneous and trunk fat and insulin resistance of young women. Design and procedures: Subjects were randomly assigned to one of the three groups: HIIE (n=15), steady-state exercise (SSE; n=15) or control (CONT; n=15). HIIE and SSE groups underwent a 15-week exercise intervention. Subjects: Forty-five women with a mean BMI of 23.22.0 kg m-2 and age of 20.22.0 years. Results: Both exercise groups demonstrated a significant improvement (P<0.05) in cardiovascular fitness. However, only the HIIE group had a significant reduction in total body mass (TBM), fat mass (FM), trunk fat and fasting plasma insulin levels. There was significant fat loss (P<0.05) in legs compared to arms in the HIIE group only. Lean compared to overweight women lost less fat after HIIE. Decreases in leptin concentrations were negatively correlated with increases in VO2peak (r=-0.57, P<0.05) and positively correlated with decreases in TBM (r=0.47; P<0.0001). There was no significant change in adiponectin levels after training. Conclusions: HIIE three times per week for 15 weeks compared to the same frequency of SSE exercise was associated with significant reductions in total body fat, subcutaneous leg and trunk fat, and insulin resistance in young women.

Aerobic fitness is associated with white matter integrity (WMI) in adults as measured by diffusion tensor imaging (DTI). This study examined the effect of an 8-month exercise intervention on WMI in children. Participants were 18 sedentary, overweight (BMI ≥85th percentile) 8- to 11-year-old children (94% Black), randomly assigned to either an aerobic exercise (n = 10) or sedentary attention control group (n = 8). Each group was offered an instructor-led after-school program every school day for approximately 8 months. Before and after the program, all subjects participated in DTI scans. Tractography was conducted to isolate the superior longitudinal fasciculus and investigate whether the exercise intervention affected WMI in this region. There was no group by time interaction for WMI in the superior longitudinal fasciculus. There was a group by time by attendance interaction, however, such that higher attendance at the exercise intervention, but not the control intervention, was associated with increased WMI. Heart rate and the total dose of exercise correlated with WMI changes in the exercise group. In the overall sample, increased WMI was associated with improved scores on a measure of attention and improved teacher ratings of executive function. This study indicates that participating in an exercise intervention improves WMI in children as compared to a sedentary after-school program.

Lifestyle combined interventions are a key strategy for preventing type-2 diabetes (T2DM) in overweight or obese subjects. In this framework, LIPOXmax individualized training, based on maximal fat oxidation [MFO], may be a promising intervention to promote fat mass (FM) reduction and prevent T2DM. Our primary objective was to compare three training programs of physical activity combined with a fruit- and vegetable-rich diet in reducing FM in overweight or obese women. A five months non-blinded randomized controlled trial (RCT) with three parallel groups in La Réunion Island, a region where metabolic diseases are highly prevalent. One hundred and thirty-six non-diabetic obese (body mass index [BMI]: 27-40 kg/m2) young women (aged 20-40) were randomized (G1: MFO intensity; G2: 60% of VO2-peak intensity; G3: free moderate-intensity at-home exercise following good physical practices). Anthropometry (BMI, bodyweight, FM, fat-free mass), glucose (fasting plasma glucose, insulin, HOMA-IR) and lipid (cholesterol and triglycerides) profiles, and MFO values were measured at month-0, month-3 and month-5. At month-5, among 109 women assessed on body composition, the three groups exhibited a significant FM reduction over time (G1: -4.1±0.54 kg; G2: -4.7±0.53 kg; G3: -3.5±0.78 kg, p<0.001, respectively) without inter-group differences (p = 0.135). All groups exhibited significant reductions in insulin levels or HOMA-IR index, and higher MFO values over time (p<0.001, respectively) but glucose control improvement was higher in G1 than in G3 while MFO values were higher in G1 than in G2 and G3. Changes in other outcome measures and inter-group differences were not significant. In our RCT the LIPOXmax intervention did not show a superiority in reducing FM in overweight or obese women but is associated with higher MFO and better glucose control improvements. Other studies are required before proposing LIPOXmax training for the prevention of T2DM in overweight or obese women. ClincialTrials.gov NCT01464073.

Tomatoes are the richest source of lycopene, a potent antioxidant. Tomato products improve antioxidant defences and reduce the risk of inflammatory diseases, at least partly, due to the presence of lycopene. Lycopene, as an anti-inflammatory agent, prevents the production of inflammatory cytokines. Obesity is a chronic inflammatory condition in which the increased level of body fat leads to an increase in circulating inflammatory mediators. We hypothesised that the consumption of a lycopene-rich food would reduce inflammation in people who are overweight or obese. A total of 106 overweight or obese female students of the Tehran University of Medical Sciences were enrolled and randomly allocated to an intervention group (n 53) or a control group (n 53) consuming 330 ml/d of tomato juice or water, respectively, for 20 d. At baseline and day 20, serum concentrations of IL-6, IL-8, high-sensitivity C-reactive protein and TNF-α were analysed by ELISA and compared between the groups. Serum concentrations of IL-8 and TNF-α decreased significantly in the intervention group compared with the control group and with baseline. Subgroup analysis indicated that this effect was confined to subjects who were overweight. Among obese subjects, serum IL-6 concentration was decreased in the intervention group compared with the control group, with no differences in IL-8 and TNF-α observed. Tomato juice reduces inflammation in overweight and obese females. Thus, increasing tomato intake may provide a useful approach for reducing the risk of inflammatory diseases such as CVD and diabetes, which are associated with obesity.

Synbiotics are known to exert multiple beneficial effects, including anti-inflammatory and antioxidant actions. The aim of this study was to evaluate the effects of synbiotic supplementation on carotid intima-media thickness (CIMT), biomarkers of inflammation, and oxidative stress in people with overweight, diabetes, and coronary heart disease (CHD). This randomized, double-blind, placebo-controlled trial was conducted and involved 60 people with overweight, diabetes, and CHD, aged 50–85 years old. Participants were randomly allocated into two groups to take either synbiotic supplements containing three probiotic bacteria spices Lactobacillus acidophilus strain T16 (IBRC-M10785), Lactobacillus casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 × 10 9  CFU/g each) plus 800 mg inulin or placebo ( n  = 30 each group) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention period to determine metabolic variables. After the 12-week intervention, compared with the placebo, synbiotic supplementation significantly reduced serum high-sensitivity C-reactive protein (hs-CRP) (− 3101.7 ± 5109.1 vs. − 6.2 ± 3163.6 ng/mL, P  = 0.02), plasma malondialdehyde (MDA) (− 0.6 ± 1.0 vs. − 0.1 ± 0.3 μmol/L, P  = 0.01), and significantly increased nitric oxide (NO) levels (+ 7.8 ± 10.3 vs. − 3.6 ± 6.9 μmol/L, P  < 0.001). We did not observe any significant changes of synbiotic supplementation on other biomarkers of oxidative stress and CIMT levels. Overall, synbiotic supplementation for 12 weeks among people with overweight, diabetes, and CHD had beneficial effects on serum hs-CRP, plasma NO, and MDA levels; however, it did not have any effect on other biomarkers of oxidative stress and CIMT levels.