Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Obesity (Silver Spring). 2019 Dec;27(12):2025-2036. doi: 10.1002/oby.22652.
Obesity is a major risk factor for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus, whereas weight loss is associated with improved health outcomes. It is therefore important to learn how adipose contraction during weight loss contributes to improved health. It was hypothesized that adipose tissue undergoing weight loss would have a unique transcriptomic profile, expressing specific genes that might improve health.
This study conducted an RNA-sequencing analysis of the epididymal adipose tissue of mice fed either a high-fat diet (HFD) or a regular rodent chow diet (RD) ad libitum for 10 weeks versus a cohort of mice fed HFD for the first 5 weeks before being swapped to an RD for the remainder of the study (swapped diet [SWAP]).
The swapped diet resulted in weight loss, with a parallel improvement in insulin sensitivity. RNA sequencing revealed several transcriptomic signatures distinct to adipose tissue in SWAP mice, distinguished from both RD and HFD adipose tissue. The analysis found a unique upregulated mRNA that encodes a secreted lipopolysaccharide-binding glycoprotein (CRISPLD2) in adipose tissue. Whereas cellular CRISPLD2 protein levels were unchanged, plasma CRIPSLD2 levels increased in SWAP mice following weight loss and could correlate with insulin sensitivity.
Taken together, these data demonstrate that CRISPLD2 is a circulating adipokine that may regulate adipocyte remodeling during weight loss.
肥胖是心血管疾病、代谢综合征和 2 型糖尿病的主要危险因素,而体重减轻与改善健康结果有关。因此,了解减肥过程中脂肪收缩如何有助于改善健康非常重要。据推测,正在减肥的脂肪组织会具有独特的转录组特征,表达可能改善健康的特定基因。
本研究对高脂肪饮食(HFD)或随意自由喂养的常规啮齿动物饲料(RD)喂养的小鼠的附睾脂肪组织进行了 RNA 测序分析,这些小鼠连续喂养 10 周,而另一组小鼠则在研究的前 5 周内用 HFD 喂养,然后在剩余时间内用 RD 喂养(交换饮食[SWAP])。
SWAP 导致体重减轻,同时胰岛素敏感性得到平行改善。RNA 测序揭示了 SWAP 小鼠脂肪组织中几个与 RD 和 HFD 脂肪组织明显不同的转录组特征。分析发现一种独特的上调 mRNA,其编码一种在脂肪组织中分泌的脂多糖结合糖蛋白(CRISPLD2)。尽管细胞内 CRISPLD2 蛋白水平没有变化,但 SWAP 小鼠在体重减轻后血浆 CRISPLD2 水平增加,并且可能与胰岛素敏感性相关。
综上所述,这些数据表明 CRISPLD2 是一种循环脂肪因子,可能在减肥过程中调节脂肪细胞重塑。