Guzzardi Maria Angela, Collado Maria Carmen, Panetta Daniele, Tripodi Maria, Iozzo Patricia
Institute of Clinical Physiology, National Research Council (CNR), 56124 Pisa, Italy.
Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), 46980 Valencia, Spain.
Metabolites. 2022 Sep 2;12(9):828. doi: 10.3390/metabo12090828.
Maternal obesity causes metabolic dysfunction in the offspring, including dysbiosis, overeating, obesity, and type 2 diabetes. Early-life phases are fundamental for developing subcutaneous (SAT) and brown adipose tissues (BAT), handling energy excesses. Imaging of F-fluorodeoxyglucose by positron emission tomography (PET) and radiodensity by computerized tomography (CT) allows assessing adipose tissue (AT) whitening and browning in vivo and the underlying metabolic efficiency. Our aim was to examine these in vivo traits in SAT and BAT concerning gut microbiota composition in 1- and 6-month-old mice born to normal (NDoff) and high-fat diet-fed dams (HFDoff), accounting for body weight responses. We found low radiodensity (high lipids) in HFDoff SAT at 1 month, relating to an increased abundance of genus in the caecum and activation of the fatty acid biosynthetic pathway. Instead, low BAT radiodensity and glucose uptake were seen in adult HFDoff. Glucose was shifted in favor of BAT at 1 month and SAT at 6 months. In adults, unclassified and , and genera were negatively related to BAT, whereas unclassified genera were related to SAT metabolism. Stratification of HFDoff based on weight-response, namely maternal induced obesity (MIO-HFDoff) or obesity-resistant (MIOR-HFDoff), showed sex dimorphism. Both subgroups were hyperphagic, but only obese mice had hyper-leptinemia and hyper-resistinemia, together with BAT dysfunction, whereas non-obese HFDoff had hyperglycemia and SAT hypermetabolism. In the caecum, unclassified (10-fold enrichment in MIO-HFDoff) and genera (4-fold deficiency in MIOR-HFDoff) were important discriminators of these two phenotypes. In conclusion, SAT whitening is an early abnormality in the offspring of HFD dams. In adult life, maternal HFD and the induced excessive food intake translates into a dimorphic phenotype involving SAT, BAT, and microbiota distinctively, reflecting maternal diet*sex interaction. This helps explain inter-individual variability in fetal programming and the higher rates of type 2 diabetes observed in adult women born to obese mothers, supporting personalized risk assessment, prevention, and treatment.
母体肥胖会导致后代出现代谢功能障碍，包括肠道菌群失调、暴饮暴食、肥胖和2型糖尿病。生命早期阶段对于皮下脂肪组织（SAT）和棕色脂肪组织（BAT）的发育以及处理能量过剩至关重要。通过正电子发射断层扫描（PET）对F-氟脱氧葡萄糖进行成像以及通过计算机断层扫描（CT）对放射密度进行成像，可以在体内评估脂肪组织（AT）的变白和变褐情况以及潜在的代谢效率。我们的目的是研究1月龄和6月龄正常饮食母鼠（NDoff）和高脂饮食母鼠（HFDoff）所产小鼠的SAT和BAT中与肠道微生物群组成相关的这些体内特征，并考虑体重反应。我们发现1月龄HFDoff小鼠的SAT放射密度较低（脂质含量高），这与盲肠中某属丰度增加以及脂肪酸生物合成途径的激活有关。相反，成年HFDoff小鼠的BAT放射密度和葡萄糖摄取较低。1月龄时葡萄糖偏向BAT，6月龄时偏向SAT。在成年小鼠中，未分类的某属以及另外两个属与BAT呈负相关，而未分类的某属与SAT代谢有关。根据体重反应对HFDoff进行分层，即母体诱导肥胖（MIO-HFDoff）或肥胖抵抗（MIOR-HFDoff），显示出性别二态性。两个亚组均食欲亢进，但只有肥胖小鼠出现高瘦素血症和高抵抗素血症，同时伴有BAT功能障碍，而非肥胖的HFDoff小鼠出现高血糖和SAT代谢亢进。在盲肠中，未分类的某属（在MIO-HFDoff中富集10倍）和另外一个属（在MIOR-HFDoff中缺乏4倍）是这两种表型的重要判别指标。总之，SAT变白是高脂饮食母鼠后代的早期异常现象。在成年期，母体高脂饮食和诱导的过度食物摄入会转化为一种二态性表型，分别涉及SAT、BAT和微生物群，反映了母体饮食*性别相互作用。这有助于解释胎儿编程中的个体差异以及肥胖母亲所生成年女性中2型糖尿病发病率较高的现象，支持个性化的风险评估、预防和治疗。
