Dennison Carol A, Eslinger Amanda J, Reimer Raylene A
Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Front Endocrinol (Lausanne). 2017 Oct 30;8:301. doi: 10.3389/fendo.2017.00301. eCollection 2017.
Maternal obesity is associated with increased risk of pregnancy complications and greater risk of obesity in offspring, but studies designed to examine preconception weight loss are limited. The objective of this study was to determine if a combined dietary [oligofructose (OFS)] and pharmacological (sitagliptin) preconception intervention could mitigate poor pregnancy outcomes associated with maternal obesity and improve offspring metabolic health and gut microbiota composition. Diet-induced obese female Sprague-Dawley rats were randomized to one of four intervention groups for 8 weeks: (1) Obese-Control (consumed control diet during intervention); (2) Obese-OFS (10% OFS diet); (3) Obese-S (sitagliptin drug); (4) Obese-OFS + S (combination treatment). Two reference groups were also included: (5) Obese-HFS (untreated obese consumed high fat/sucrose diet throughout study); (6) Lean-Control (lean reference group that were never obese and consumed control diet throughout). Offspring consumed control diet until 11 weeks of age followed by HFS diet until 17 weeks of age. The Obese-OFS + S rats lost weight during the intervention phase whereas the OFS and S treatments attenuated weight gain compared with Obese-HFS ( < 0.05). Gestational weight gain was lowest in Obese-OFS + S rats and highest in Obese-HFS rats ( < 0.05). Prepregnancy intervention did not affect reproductive parameters but did affect pregnancy outcomes including litter size. Male Obese-OFS offspring had significantly lower percent body fat than Obese-HFS at 17 weeks. Female Obese-S and Obese-OFS offspring had significantly lower fasting glucose at 17 weeks compared with Obese-Control and Obese-HFS. cluster XI was higher in Obese-HFS and Obese-S dams at birth compared with all other groups. Dams with an adverse pregnancy outcome had significantly lower ( = 0.035) spp. compared with dams with normal or small litters. At weaning, male offspring of Obese-HFS had higher levels of than all other groups except Obese-S and female Obese-HFS offspring had higher compared with all other groups. At 11 and 17 weeks of age, / spp. was significantly lower in male and female offspring of Obese-HFS dams compared with all other groups except Obese-OFS + S. Modest weight loss induced with a diet-drug combination did not affect maternal fecundity but did have sex-specific effects on offspring adiposity and glycemia that may be linked to changes in offspring microbiota.
孕妇肥胖与妊娠并发症风险增加以及后代肥胖风险增大相关，但旨在研究孕前体重减轻的研究有限。本研究的目的是确定联合饮食干预（低聚果糖）和药物干预（西他列汀）的孕前干预措施是否可以减轻与孕妇肥胖相关的不良妊娠结局，并改善后代的代谢健康和肠道微生物群组成。将饮食诱导肥胖的雌性斯普拉格-道利大鼠随机分为四个干预组之一，为期8周：（1）肥胖对照组（干预期间食用对照饮食）；（2）肥胖-低聚果糖组（10%低聚果糖饮食）；（3）肥胖-西他列汀组（西他列汀药物）；（4）肥胖-低聚果糖+西他列汀组（联合治疗）。还纳入了两个参照组：（5）肥胖-高脂高糖组（未治疗的肥胖大鼠在整个研究期间食用高脂肪/高糖饮食）；（6）瘦对照组（从未肥胖且在整个研究期间食用对照饮食的瘦参照组）。后代在11周龄前食用对照饮食，之后在17周龄前食用高脂高糖饮食。肥胖-低聚果糖+西他列汀组大鼠在干预阶段体重减轻，而低聚果糖和西他列汀治疗组与肥胖-高脂高糖组相比体重增加减缓（P<0.05）。肥胖-低聚果糖+西他列汀组大鼠孕期体重增加最低，肥胖-高脂高糖组大鼠最高（P<0.05）。孕前干预不影响生殖参数，但确实影响包括产仔数在内的妊娠结局。肥胖-低聚果糖组雄性后代在17周龄时体脂百分比显著低于肥胖-高脂高糖组。与肥胖对照组和肥胖-高脂高糖组相比，肥胖-西他列汀组和肥胖-低聚果糖组雌性后代在17周龄时空腹血糖显著降低。出生时，肥胖-高脂高糖组和肥胖-西他列汀组母鼠的XI簇高于所有其他组。妊娠结局不良的母鼠的某菌属水平显著低于产仔数正常或较少的母鼠（P=0.035）。断奶时，肥胖-高脂高糖组雄性后代的某菌属水平高于所有其他组，但肥胖-西他列汀组和肥胖-高脂高糖组雌性后代除外，且肥胖-高脂高糖组雌性后代也高于所有其他组。在11周龄和17周龄时，与除肥胖-低聚果糖+西他列汀组外的所有其他组相比，肥胖-高脂高糖组母鼠的雄性和雌性后代的某菌属水平显著降低。饮食-药物联合诱导的适度体重减轻不影响母体生育力，但对后代肥胖和血糖有性别特异性影响，这可能与后代微生物群的变化有关。
