Objective To investigate the variations in body weight, food intake and body composition of both male and female C57BL/6J mice during a diet-induced obesity (DIO) model with high-fat diet (HFD) feeding. Design and Methods Mice were individually housed and fed ad libitum either a low-fat diet (LFD, 10% calories from fat; n=15 male, n=15 female) or high-fat diet (HFD, 45% calories from fat; n=277 male, n=278 female) from 8 to 43 weeks of age. Body weight, food intake and body composition were routinely measured. Results Body weight was significantly increased with HFD (vs. LFD) in males from week 14 (p=0.0221) and in females from week 27 (P=0.0076). Fat mass and fat-free mass of all groups were significantly increased over time (all p<0.0001), with a large variation observed in fat mass. Baseline fat mass, fat-free mass and daily energy intake were significant predictors of future body weight for both sexes (p<0.0001). Baseline fat mass was a significant predictor of future body fat (p<0.0001). Conclusions Both males and females have large variations in fat mass, and this variability increases over time, while that of fat-free mass remains relatively stable. Sex differences exist in HFD responses and multivariate predicting models of body weight.

We provide arguments to the debate question and update a previous meta-analysis with recently published studies on effects of sugar-sweetened beverages (SSBs) on body weight/composition indices (BWIs). We abstracted data from randomized controlled trials examining effects of consumption of SSBs on BWIs. Six new studies met these criteria: 1) human trials, 2) 3 weeks duration, 3) random assignment to conditions differing only in consumption of SSBs, and 4) including a BWI outcome. Updated meta-analysis of a total of seven studies that added SSBs to persons’ diets showed dose-dependent increases in weight. Updated meta-analysis of eight studies attempting to reduce SSB consumption showed an equivocal effect on BWIs in all randomized subjects. When limited to subjects overweight at baseline, meta-analysis showed a significant effect of roughly 0.25 standard deviations (more weight loss/less weight gain) relative to controls. Evidence to date is equivocal in showing that decreasing SSB consumption will reduce the prevalence of obesity. Although new evidence suggests that an effect may yet be demonstrable in some populations, the integrated effect size estimate remains very small and of equivocal statistical significance. Problems in this research area and suggestions for future research are highlighted.

Background Public health and clinical interventions for obesity in free-living adults may be diminished by individual compensation for the intervention. Approaches to predict weight outcomes do not account for all mechanisms of compensation, so they are not well suited to predict outcomes in free-living adults. Our objective was to quantify the range of compensation in energy intake or expenditure observed in human randomized controlled trials (RCTs). Methods We searched multiple databases (PubMed, CINAHL, SCOPUS, Cochrane, ProQuest, PsycInfo) up to August 1, 2012 for RCTs evaluating the effect dietary and/or physical activity interventions on body weight/composition. Inclusion Criteria: subjects per treatment arm ≥ 5; ≥1 week intervention; a reported outcome of body weight /body composition; the intervention was either a prescribed amount of over- or underfeeding and/or supervised or monitored physical activity was prescribed; ≥ 80% compliance; an objective method was used to verify compliance with the intervention (e.g., observation, electronic monitoring). Data were independently extracted and analyzed by multiple reviewers with consensus reached by discussion. We compared observed weight change to predicted weight change using two models that predict weight change accounting only for metabolic compensation. Findings Twenty-eight studies met inclusion criteria. Overfeeding studies indicate 96% less weight gain than expected if no compensation occurred. Dietary restriction and exercise studies may result in up to 12–44% and 55–64% less weight loss than expected, respectively, under an assumption of no behavioral compensation. Interpretation Compensation is substantial even in high-compliance conditions, resulting in far less weight change than would be expected. The simple algorithm we report allows for more realistic predictions of intervention effects in free-living populations by accounting for the significant compensation that occurs.

Broadly targeted cellular immune responses are thought to be important for controlling replication of human and simian immunodeficiency viruses (HIV and SIV). However, eliciting such responses by vaccination is complicated by immunodominance, the preferential targeting of only a few of the many possible epitopes of a given antigen. This phenomenon may be due to the coexpression of dominant and subdominant epitopes by the same antigen-presenting cell and may be overcome by distributing these sequences among several different vaccine constructs. Accordingly, we tested whether vaccinating rhesus macaques with "minigenes" encoding fragments of Gag, Vif, and Nef resulted in broadened cellular responses capable of controlling SIV replication. We delivered these minigenes through combinations of recombinant Mycobacterium bovis BCG (rBCG), electroporated recombinant DNA (rDNA) along with an interleukin-12 (IL-12)-expressing plasmid (EP rDNA plus pIL-12), yellow fever vaccine virus 17D (rYF17D), and recombinant adenovirus serotype 5 (rAd5). Although priming with EP rDNA plus pIL-12 increased the breadth of vaccine-induced T-cell responses, this effect was likely due to the improved antigen delivery afforded by electroporation rather than modulation of immunodominance. Indeed, Mamu-A*01؉ vaccinees mounted CD8 ؉ T cells directed against only one subdominant epitope, regardless of the vaccination regimen. After challenge with SIVmac239, vaccine efficacy was limited to a modest reduction in set point in some of the groups and did not correlate with standard T-cell measurements. These findings suggest that broad T-cell responses elicited by conventional vectors may not be sufficient to substantially contain AIDS virus replication. IMPORTANCEImmunodominance poses a major obstacle to the generation of broadly targeted, HIV-specific cellular responses by vaccination. Here we attempted to circumvent this phenomenon and thereby broaden the repertoire of SIV-specific cellular responses by vaccinating rhesus macaques with minigenes encoding fragments of Gag, Vif, and Nef. In contrast to previous mouse studies, this strategy appeared to minimally affect monkey CD8 ؉ T-cell immundominance hierarchies, as seen by the detection of only one subdominant epitope in Mamu-A*01 ؉ vaccinees. This finding underscores the difficulty of inducing subdominant CD8 ؉ T cells by vaccination and demonstrates that strategies other than gene fragmentation may be required to significantly alter immunodominance in primates. Although some of the regimens tested here were extremely immunogenic, vaccine efficacy was limited to a modest reduction in set point viremia after challenge with SIVmac239. No correlates of protection were identified. These results reinforce the notion that vaccine immunogenicity does not predict control of AIDS virus replication.

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