Li Yan, Yu Shan, Chen Lulu, Hu Xiang, Zheng Juan, Deng Xiuling
1Department of Endocrinology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, 046000 People's Republic of China.
2Department of anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 People's Republic of China.
Nutr Metab (Lond). 2019 Feb 11;16:11. doi: 10.1186/s12986-019-0336-9. eCollection 2019.
Catch-up growth in adult (CUGA) is characterized by visceral fat accumulation, ectopic lipid deposition and insulin resistance (IR). Here, we investigated the determinants of these pathophysiological consequences of CUGA.
Rats were divided into different groups: control rats were offered normal chow ad libitum (AL), while experimental rats were put on 4-week caloric restriction (CR) initially, followed by regaining weight-matched normal chow (RN) in the RN group. General characteristics of lipid metabolism, expression level of genes in visceral adipose tissue (VAT), and glucose infusion rate (GIR) by the hyperinsulinemic-euglycemic clamp were examined.
After CR, percentage of abdominal fat mass (AFM%) was lower in the RN group than in the AL group but no difference was observed in serum non-esterified fatty acid (NEFA). Expression of fat-specific protein 27 (FSP27) was decreased in the RN group, while the expression of peroxisome proliferator-activated receptors γ (PPARγ), the key lipogenic gene, was increased. After refeeding, AFM% increased over time and serum NEFA persistently elevated in the RN group. Ectopic triglyceride contents were increased whereas insulin sensitivity was impaired. The expression of FSP27 did not follow the increase in the expression of PPARγ. Additionally, we observed a sustained increase in the expression of ATGL and CGI-58 in VAT in the RN group compared with the AL group after CR and refeeding, and a persistent shift-to-the-left of adipocyte size distribution accompanied by enhanced lipogenesis during CUGA.
The persistent CR-induced imbalance of lipogenesis/fat storage capacity might be responsible for the CUGA-associated metabolic disorders.
成人追赶生长（CUGA）的特征是内脏脂肪堆积、异位脂质沉积和胰岛素抵抗（IR）。在此，我们研究了CUGA这些病理生理后果的决定因素。
将大鼠分为不同组：对照组大鼠随意给予正常饲料（AL），而实验组大鼠最初进行4周的热量限制（CR），随后在恢复体重组（RN）给予体重匹配的正常饲料。通过高胰岛素-正常血糖钳夹技术检测脂质代谢的一般特征、内脏脂肪组织（VAT）中基因的表达水平以及葡萄糖输注率（GIR）。
CR后，RN组腹部脂肪量百分比（AFM%）低于AL组，但血清非酯化脂肪酸（NEFA）无差异。RN组脂肪特异性蛋白27（FSP27）的表达降低，而关键脂肪生成基因过氧化物酶体增殖物激活受体γ（PPARγ）的表达增加。再喂养后，RN组AFM%随时间增加，血清NEFA持续升高。异位甘油三酯含量增加，而胰岛素敏感性受损。FSP27的表达未随PPARγ表达的增加而增加。此外，与AL组相比，我们观察到RN组在CR和再喂养后VAT中ATGL和CGI-58的表达持续增加，并且在CUGA期间脂肪细胞大小分布持续左移，伴有脂肪生成增强。
持续的CR诱导的脂肪生成/脂肪储存能力失衡可能是CUGA相关代谢紊乱的原因。
