Joanne Doucette

Introduction: Obesity presents with structural and functional hypothalamic dysfunction. However, it is unclear whether weight loss can lead to hypothalamic changes. We therefore aimed to conduct a systematic review and meta-analysis to determine the effect of body mass reduction in obese individuals on hypothalamic structure and function.Methods: PubMed, Embase, and Cochrane databases were searched for studies that reported the change in hypothalamic structure and function after weight loss. Qualitative and quantitative analyses were performed on magnetic resonance imaging techniques, medio-basal hypothalamus T2-relaxation time, blood oxygen level dependent (BOLD) contrast, voxel-based morphometry (VBM), and biomarkers including glucose, insulin, leptin, ghrelin, and inflammatory markers of interleukins. Mean differences between pre- and post-weight loss and 95% confidence intervals (CI) were pooled using random-effects models.Results: Thirteen pre-post studies were included, of which six accounted for the meta-analysis. Studies showed a favorable decrease in T2-relaxation time (n = 1), favorable change in hypothalamic activity after weight loss on BOLD contrast (n = 4), with higher peak activities after surgical weight loss (n = 2). No differences were found in the gray matter density of the hypothalamus, on VBM (n = 1). Pooled mean differences between pre- and post-surgical weight loss revealed a decrease of 8.53 mg/dl (95%CI: 5.17, 11.9) in glucose, 7.73 pmol/l (95%CI: 5.07, 10.4) in insulin, 15.5 ng/ml (95%CI: 9.40, 21.6) in leptin, 142.9 pg/ml (95%CI: 79.0, 206.8) in ghrelin, and 9.43 pg/ml (95%CI: -6.89, 25.7) in IL-6 level.Conclusion: Our study showed weight reduction in obesity lead to limited structural change and significant functional changes in the hypothalamus.

The reproducibility and translation of neuroscience research is assumed to be undermined by introducing environmental complexity and heterogeneity. Rearing laboratory animals with minimal (if any) environmental stimulation is thought to control for biological variability but may not adequately test the robustness of our animal models. Standard laboratory housing is associated with reduced demonstrations of species typical behaviors and changes in neurophysiology that may impact the translation of research results. Modest increases in environmental enrichment (EE), mitigate against insults used to induce animal models of disease, directly calling into question the translatability of our work. This may in part underlie the disconnect between preclinical and clinical research findings. Enhancing environmental stimulation for our model organisms promotes ethological natural behaviors but may simultaneously increase phenotypic trait variability. To test this assumption, we conducted a systematic review and evaluated coefficients of variation between EE and standard housed mice and rats. Given findings of suboptimal reporting of animal laboratory housing conditions, we also developed a methodological reporting table for enrichment use in neuroscience research. Our data show that animals housed in environmental enrichment were not more variable than those in standard housing. Therefore, environmental heterogeneity introduced into the laboratory, in the form of enrichment, does not compromise data integrity. Overall, human life is complicated and by embracing such nuanced complexity into our laboratories we may paradoxically improve upon the rigor and reproducibility of our research. Significance Statement: Environmental complexity is thought to increase phenotypic variability, undermining research translation. We conducted a systematic review and compared coefficients of variation between environmentally enriched and standard housed laboratory animals. Despite there being no differences in variability across several phenotypic traits, there are stark contrasts in the display of ethological natural behaviors between these housing conditions. Environmental enrichment is recognized as being beneficial for animal welfare and mitigates against insults used to induce animal models of disease. In contrast, standard laboratory cages are recognized as being impoverished and ‘unnatural’. From these observations, it is apparent that our current “gold standard” caging system is not a true control condition as it does not adequately test the robustness of our animal models.

(2019). The Library Staff Development Handbook: How to Maximize Your Library’s Most Important Resource. Journal of Electronic Resources in Medical Libraries. Ahead of Print.