Variations in body weight, food intake and body composition after long-term high-fat diet feeding in C57BL/6J mice.

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 model with high-fat diet (HFD) feeding. 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 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.

Vaccination with Gag, Vif, and Nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239.

UNLABELLED: 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. IMPORTANCE: Immunodominance 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.