Guangdong Laboratory of Lingnan Modern Agriculture, Guangdong Province Key Laboratory of Animal Nutritional Regulation and National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA.
Mol Biotechnol. 2024 Sep;66(9):2322-2331. doi: 10.1007/s12033-023-00828-6. Epub 2023 Aug 29.
Tamoxifen (TAM) is commonly administered to a variety of inducible or conditional transgenic mice that contain Cre recombinase fused with ER. While the impacts of adult TAM treatment are well documented in the field of adipose biology, the long-term effects of postnatal TAM treatment on adult life are still understudied. In this study, we investigated whether postnatal TAM treatment had long-lasting effects on adult body composition and adiposity in male and female mice, fed either with chow or a high-fat diet (HFD). We found that postnatal, but not adult, TAM treatment had long-lasting impacts on female mice, resulting in lower body weight, lower fat mass, and smaller adipocytes. In contrast, postnatal exposure to TAM impaired male but not female cold-induced adipose beiging capacity. Interestingly, upon HFD feeding, the sex-dependent effects of TAM on adult life disappeared, and both female and male mice showed a more obese phenotype with impaired glucose tolerance. These findings suggest that postnatal TAM injection exerts a long-lasting impact on adipose tissue in adult life in a sex- and diet-dependent manner.
他莫昔芬(TAM)常用于包含与 ER 融合的 Cre 重组酶的各种诱导型或条件性转基因小鼠。虽然成年 TAM 治疗的影响在脂肪生物学领域已有充分记录,但 TAM 对成年后的长期影响仍研究不足。在这项研究中,我们研究了 TAM 处理是否对雄性和雌性小鼠的成年身体组成和肥胖有长期影响,这些小鼠分别用标准饮食或高脂肪饮食(HFD)喂养。我们发现,TAM 处理仅在幼年期而非成年期对雌性小鼠有长期影响,导致体重降低、脂肪量减少和脂肪细胞变小。相反,TAM 处理会损害雄性但不会损害雌性的冷诱导脂肪褐变能力。有趣的是,在 HFD 喂养时,TAM 对成年期的性别依赖性影响消失,雌雄小鼠均表现出肥胖表型和葡萄糖耐量受损。这些发现表明,TAM 注射在幼年期对成年期的脂肪组织有持久的影响,其影响具有性别和饮食依赖性。