Influence of age, reproductive cycling status, and menstruation on the vaginal microbiome in baboons (Papio anubis)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111197/1/ajp22378.pd

Insulin Resistance and Metabolic Hepatocarcinogenesis with Parent-of-Origin Effects in A×B Mice

Insulin resistance is a defining feature of metabolic syndrome and type 2 diabetes mellitus but also may occur independently of these conditions. Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of these disorders, increases the risk of hepatocellular carcinoma (HCC). However, mechanisms linking hyperinsulinemia to NAFLD and HCC require clarification. We describe a novel model of primary insulin resistance and HCC with strong parent-of-origin effects. Male AB6F1 (A/JCr dam × C57BL/6 sire) but not B6AF1 (B6 dam × A/J sire) mice developed spontaneous insulin resistance, NAFLD, and HCC without obesity or diabetes. A survey of mitochondrial, imprinted, and sex-linked traits revealed modest associations with X-linked genes. However, a diet-induced obesity study, including B6.A chromosome substitution–strain (consomic) mice, showed no segregation by sex chromosome. Thus, parent-of-origin effects were specified within the autosomal genome. Next, we interrogated mechanisms of insulin-associated hepatocarcinogenesis. Steatotic hepatocytes exhibited adipogenic transition characterized by vacuolar metaplasia and up-regulation of vimentin, adipsin, fatty acid translocase (CD36), peroxisome proliferator–activated receptor-γ, and related products. This profile was largely recapitulated in insulin-supplemented primary mouse hepatocyte cultures. Importantly, pyruvate kinase M2, a fetal anabolic enzyme implicated in the Warburg effect, was activated by insulin in vivo and in vitro. Thus, our study reveals parent-of-origin effects in heritable insulin resistance, implicating adipogenic transition with acquired anabolic metabolism in the progression from NAFLD to HCC.National Institutes of Health (U.S.) (NIH grant AA016563)National Institutes of Health (U.S.) (NIH grant CA067529)National Institutes of Health (U.S.) (NIH grant P01CA0267)National Institutes of Health (U.S.) (NIH grant P30ES02109)National Institutes of Health (U.S.) (NIH grant RR007036)National Institutes of Health (U.S.) (NIH grant CA158661)National Institutes of Health (U.S.) (NIH grant CA016086

Impact of a hormone‐releasing intrauterine system on the vaginal microbiome: a prospective baboon model

Background Use of a levonorgestrel‐releasing intrauterine system ( LNG ‐ IUS ) in humans may alter vaginal microbial populations and susceptibility to pathogens. This study evaluated the time‐dependent effects of an LNG ‐ IUS on the vaginal microbiome of the baboon, a useful animal model for reproductive studies. Methods Levonorgestrel‐releasing intrauterine systems were inserted into three reproductively mature, female baboons. The animals were evaluated for 6 months by physical examination and G ram‐stained cytology. The vaginal microbiota was characterized at each timepoint by culture‐independent analysis of the 16 S rRNA ‐encoding gene. Results Each baboon harbored a diverse vaginal microbiome. Interindividual variation exceeded intra‐individual variation. Diversity declined over time in one baboon and showed mild fluctuations in the other two. There were no significant community differences from early to late post‐ LNG ‐ IUS placement. Conclusions The baboon vaginal microbiome is unique to each individual and is polymicrobial. In this pilot study, the vaginal microbiome remained stable from early to late post‐ LNG ‐ IUS placement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106666/1/jmp12090.pd