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PLIN2-induced ectopic lipid accumulation promotes muscle ageing in gregarious locusts

Nature Ecology & Evolution volume 7, pages 914–926 (2023)Cite this article

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Abstract

Ageing plasticity represents the flexibility of the ageing process in response to non-genetic factors, occurring commonly in animals. However, the regulatory mechanisms underlying ageing plasticity are largely unclear. The density-dependent polyphenism of locusts, Locusta migratoria, displays dramatic lifespan divergence between solitary and gregarious phases, providing a useful system for studying ageing plasticity. Here, we found that gregarious locusts displayed faster locomotor deficits and increased muscle degeneration on ageing than solitary locusts. Comparative transcriptome analysis in flight muscles revealed significant differences in transcriptional patterns on ageing between two phases. RNA interference screening showed that the knockdown of the upregulated PLIN2 gene significantly relieved the ageing-related flight impairments in gregarious locusts. Mechanistically, the gradual upregulation of PLIN2 could induce the accumulation of ectopic lipid droplets and triacylglycerols in flight muscles during the ageing process. Further experiments suggested that ectopic lipid accumulation led to an ageing-related β-oxidation decline through limiting fatty acid transport and content. These findings reveal the key roles of lipid metabolism in the differences of muscle ageing between solitary and gregarious locusts and provide a potential mechanism underlying environment-induced muscle ageing plasticity.

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Fig. 1: Phase-differential muscle ageing in the migratory locust.
Fig. 2: Differences in upregulated DEGs in aged muscles between solitary and gregarious locusts.
Fig. 3: PLIN2 upregulation triggers ageing-related accumulation of lipid droplets and TAGs.
Fig. 4: PLIN2 upregulation reduces fatty acid transport, content and oxidation in the flight muscles of old gregarious locusts.
Fig. 5: Ectopic lipid accumulation mediates the effects of PLIN2 upregulation on disrupted lipid metabolism in old gregarious locusts.
Fig. 6: Regulatory model of PLIN2-induced ectopic lipid accumulation in phase-dependent muscle ageing plasticity.

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Data availability

All data and materials generated in this study are available in the main text, supplementary materials and source data. The RNA-seq data were deposited at the NCBI Sequence Read Archive under BioProject no. PRJNA562411 and the National Genomics Data Center under BioProject no. CRA006718. Source data are provided with this paper.

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Acknowledgements

We thank J. Ge and D. Ding for their comments and suggestions to improve the manuscript, and P. Yang and B. Du for assistance with the Python and R software. We thank S. Liu, W. Cui and J. Yu for preparing the locusts. We thank iPheome (Yunpukang) Biotechnology for the lipidomic analyses. This work was supported by the National Key R&D Program of China no. 2022YFD1400500, the National Natural Science Foundation of China (grant nos. 31930012, 32088102 and 32100388), the China Postdoctoral Science Foundation (no. 2021M703204) and Youth Innovation Promotion Association CAS (no. 2021079).

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  1. These authors contributed equally: Siyuan Guo, Li Hou.

Authors and Affiliations

  1. State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

    Siyuan Guo, Li Hou, Liushu Dong, Xin Nie, Le Kang & Xianhui Wang

  2. CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, China

    Li Hou, Le Kang & Xianhui Wang

  3. Beijing Institutes of Life Science, Chinese Academy of Sciences, Chaoyang District, Beijing, China

    Le Kang

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Contributions

S.G., L.K. and X.W. designed the research. S.G., L.H. and L.D. performed the research. S.G. and X.N. contributed the analytical tools. S.G. and X.W. analysed the data. S.G., L.H., L.K. and X.W. wrote the paper.

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Correspondence to Le Kang or Xianhui Wang.

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Extended data

Extended Data Fig. 1 Abundance detection of total ROS in flight muscles of solitary and gregarious locusts during ageing.

n = 6 for the comparison between 14-D and 42-D solitary locusts and between 14-D and 28-D gregarious locusts, n = 7 for the comparison between 28-D solitary and 28-D gregarious locusts. Data are mean ± s.e.m. Significant differences are analysed using two-tailed unpaired t test.

Source data

Extended Data Fig. 2 RNAi efficiency of four ageing-related genes in muscles.

n = 6 for all conditions. Data are mean ± s.e.m. Significant differences are analysed using two-tailed unpaired t test.

Source data

Extended Data Fig. 3 Expression levels of PLIN2 during ageing in flight muscles of solitary and gregarious locusts at different population densities.

n = 5 for 28-d gregarious locusts (rearing density = 200 individuals per cage), and n = 6 for all other conditions. Data are mean ± s.e.m. Different letters corresponding to the population density indicate statistically significant differences across age groups using one-way ANOVA (Tukey’s multiple comparisons test, P < 0.05).

Source data

Extended Data Fig. 4 Lifespan of gregarious (G) and solitary (S) locust males after PLIN2 knockdown.

Blue and red lines represent the survival curves of dsGFP and dsPLIN2-injected locusts, respectively. n = 33 (dsGFP, gregarious locusts), 33 (dsPLIN2, gregarious locusts), 36 (dsGFP, solitary locusts) and 36 (dsPLIN2, solitary locusts). The P-value is determined by the Gehan–Breslow–Wilcoxon test (P = 0.670 for G, and 0.748 for S).

Source data

Extended Data Fig. 5 Pie chart of metabolite chemical classes structurally annotated.

In total, 593 lipid metabolites are characterised.

Source data

Extended Data Fig. 6 Gradual upregulation of PLIN2-induced ectopic lipids during ageing is closely related to muscle deficiency in gregarious locusts.

a, Measuring expression levels of PLIN2 during 21–28 D in flight muscles of gregarious locusts by qPCR. n = 5 for 14 D and 6 for all other conditions. b, LD staining and quantification in flight muscles of gregarious locusts during 21–28 D. Blue indicates cell nuclei stained by Hoechest 33342, and green indicates lipid droplets stained by BODIPYTM 493/503. Scale bars represent 50 μm. n = 5 for all conditions. c, Abundance detection of TAG in flight muscles of gregarious locusts during 21–28 d. n = 6 for all conditions. d, Detection of the TAG level, flight performance and ATP level in gregarious locusts at 14, 21, 23, 25 and 28 d after PLIN2 knockdown. For the TAG assays, n = 6 for all conditions. For the flight performance assays, n = 33 (14-d, dsGFP), 34 (14-d, dsPLIN2), 36 (21-d, dsGFP), 36 (21-d, dsPLIN2), 33 (23-d, dsGFP), 36 (23-d, dsPLIN2), 35 (25-d, dsGFP), 34 (25-d, dsPLIN2), 28 (28-d, dsGFP) and 29 (29-d, dsPLIN2). For the ATP assays, n = 6 for all conditions. For a–d, data are mean ± s.e.m. Significant differences are analysed using one-way ANOVA for multigroup comparisons (P < 0.05) (a–c) and two-tailed unpaired t test for two-group comparisons (d).

Source data

Extended Data Fig. 7 Venn diagram of DEGs after PLIN2 knockdown and during ageing in gregarious locusts.

a, Venn diagram of DEGs between upregulated genes after PLIN2 knockdown and downregulated DEGs during 21–28 d in gregarious locusts. b, Venn diagram of DEGs between downregulated genes after PLIN2 knockdown and upregulated DEGs during 21–28 d in gregarious locusts.

Source data

Extended Data Fig. 8 FABP expression in flight muscles of solitary and gregarious locusts during ageing and of gregarious locusts after PLIN2 knockdown.

a, Determination of FABP protein level by analysing band intensity on western blot images. n = 3 for S and G, 4 for PLIN2 knockdown. Significant differences are revealed using one-way ANOVA for multigroup comparisons (P < 0.05) and two-tailed unpaired t test for two-group comparison. b, Determination of FABP mRNA level by analysing RPKM value from transcriptomes. Data are mean ± s.e.m. The values that indicate statistically significant differences are the adjusted P-value with false discovery rate correction.

Source data

Extended Data Fig. 9 RNAi efficiency of ATGL in muscles.

n = 6 for both conditions. Data are mean ± s.e.m. Significant difference is analysed using two-tailed unpaired t test.

Source data

Supplementary information

Supplementary Information

Supplementary Fig. 1.

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Supplementary Tables 1–6

Table 1 RPKM values of all genes and statistical analyses in the transcriptomes. Table 2 PC scores of genes based on the AC-PCA analyses. Table 3 Abundance of lipid species in lipidomes. Table 4 Abundance of fatty acid species in the LC–MS/MS analyses. Table 5 Primers used in the qPCR and RNAi experiments. Table 6 Abbreviations.

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Guo, S., Hou, L., Dong, L. et al. PLIN2-induced ectopic lipid accumulation promotes muscle ageing in gregarious locusts. Nat Ecol Evol 7, 914–926 (2023). https://doi.org/10.1038/s41559-023-02059-z

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