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Decrease in leptin mediates rat bone metabolism impairments during high-fat diet-induced catch-up growth by modulating the OPG/RANKL balance

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Abstract

Due to catch-up growth (CUG), there are adverse effects on human health. However, there is little information about its influence on bone metabolism. This study aimed to investigate the effects of leptin on bone metabolism and formation during high-fat diet (HFD)-induced CUG. We randomly divided male Wistar rats (5 weeks old) into four groups: control (CTL), caloric restriction and normal chow (RN), caloric restriction (4 weeks), and HFD (RH), and RH + leptin antagonist (RH + LEPA). We monitored body weights, biochemical markers, and epididymal and perirenal fat in these rats. We then performed Hematoxylin and Eosin (H&E) staining to evaluate bone metabolism. We detected osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa b ligand (RANKL) by qRT-PCR and immunohistochemistry (IHC). We found that HFD increased the body weights in rats. In RN, RH, and RH + LEPA groups, major biochemical markers of bone metabolism in rat serum were significantly altered. We found that epididymal and perirenal fat tissues of RH and RH + LEPA groups were higher than those in the RN group. Severe bone formation impairment in the distal diaphysis and metaphysis of the left femora and lumbar vertebra was seen in the RH group compared to RN, which was even aggravated by a leptin antagonist. OPG in the left femora and lumbar vertebra was lower in RH than the RN group. The leptin antagonist decreased OPG during CUG in the RH group, whereas RANKL expression showed an opposite alteration. During HFD-induced CUG, bone formation was mediated by OPG and RANKL and was affected by the leptin content.

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Funding

The work is supported by Basic ability importment project of Yong and Middle-aged teachers in Guangxi Zhuang autonomous region (No. 2017KY0487).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China

    Xiaoling Liu, Ning Xia & Qiong Yang

  2. Department of Endocrinology and Metabolism. The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China

    Yuzhen Liang

  3. Department of Orthopedics, The Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China

    Weiming Liu

  4. Department of Clinical Laboratory, The Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China

    Caimei Wang

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  1. Xiaoling Liu
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Contributions

NX conceived and designed the experiments. XLL, YZL, WML and QY performed the experiments and XLL, YZL and CMW analyzed the data. NX and XLL wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Ning Xia.

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Liu, X., Liang, Y., Xia, N. et al. Decrease in leptin mediates rat bone metabolism impairments during high-fat diet-induced catch-up growth by modulating the OPG/RANKL balance. 3 Biotech 11, 103 (2021). https://doi.org/10.1007/s13205-021-02658-2

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