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Long-term dietary DHA intervention prevents telomere attrition and lipid disturbance in telomerase-deficient male mice

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Abstract

Purpose

Previous evidence indicated anti-ageing potential of docosahexaenoic acid (DHA), but the underlying mechanism remains unclear. We investigated protective effect of DHA on telomere attrition and lipid disturbance in male mice with premature ageing caused by telomerase deficiency.

Methods

Wild-type (WT) and fourth-generation telomerase-deficient (G4 Terc−/−, Terc knockout, KO) male mice (C57BL/6, 2 months old) were fed control diet (WT-C and KO-C groups) or DHA-enriched diet containing 0.80% DHA by weight (WT-DHA and KO-DHA groups) for 10 months. The ageing phenotypes and metabolic level [carbon dioxide emission, oxygen consumption, and respiratory exchange ratio (RER)] were assessed at the end of the experiment. Telomere length in various tissues and the hepatic gene and protein expression for regulating lipid synthesis and lipolysis were measured. Data were tested using one- or two-factor ANOVA.

Results

In KO male mice, DHA prevented weight loss, corrected high RER, and reduced fat loss. Telomere shortening was reduced by 22.3%, 25.5%, and 13.5% in heart, liver, and testes of the KO-DHA group compared with those in the KO-C group. The KO-DHA group exhibited higher gene transcription involved in glycerol-3-phosphate pathway [glycerol-3-phosphate acyltransferase (Gpat)], lower gene expression of β-oxidation [carnitine palmitoyltransferase 1a (Cpt1a)], and upregulation of proteins in lipid synthesis [mammalian target of rapamycin complex 1 (mTORC1) and sterol responsive element binding protein 1 (SREBP1)] in liver than the KO-C group.

Conclusion

Long-term DHA intervention attenuates telomere attrition and promotes lipid synthesis via the tuberous sclerosis complex 2 (TSC2)-mTORC1-SREBP1 pathway in KO male mice.

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Data availability

The data in our present study can be made available after corresponding author’s review of request for data.

Abbreviations

Acaca:

Acetyl-CoA carboxylase alpha

ALA:

α-Linolenic acid

Apat:

Acyl-glycerol-phosphate acyltransferase

CAC:

Cancer-associated cachexia

Cpt1a:

Carnitine palmitoyltransferase 1A

Dgat:

Diacylglycerol acyltransferase

DHA:

Docosahexaenoic acid

Fasn:

Fatty acid synthase

G4 Terc −/− :

Fourth generation of telomerase deficient

Gpat:

Glycerol-3-phosphate acyltransferase

GSK3β:

Glycogen synthase kinase-3β

H&E:

Haematoxylin and eosin

Lcad:

Long-chain acyl-coenzyme A dehydrogenase

Mcad:

Medium-chain acyl-coenzyme A dehydrogenase

MEF:

Murine embryonic fibroblast

mTOR:

Mammalian target of rapamycin

mTORC1:

MTOR complex 1

NMR:

Nuclear magnetic resonance

PUFA:

Polyunsaturated fatty acid

Q-FISH:

Quantitative fluorescence in situ hybridization

RER:

Respiratory exchange ratio

ROS:

Reactive oxygen species

S6K1:

S6 Kinase 1

SREBP1:

Sterol responsive element binding protein 1

TG:

Triacylglycerol

TSC2:

Tuberous sclerosis complex 2

WT:

Wild type

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Acknowledgements

We gratefully thank the Zhejiang Provincial Natural Science Foundation of China (Grant No. LR18C200001).

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Author notes

  1. Jingnan Chen and Shanyun Wu have contributed equally to the research.

Authors and Affiliations

  1. National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China

    Jingnan Chen, Shanyun Wu, Yuqi Wu, Pan Zhuang & Yu Zhang

  2. Department of Nutrition, School of Public Health, Department of Endocrinology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China

    Jingjing Jiao

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Contributions

JNC, YZ and JJJ designed the research; JNC, SYW and YQW conducted the experimental work and data acquisition; JNC and SYW analyzed data; JNC and SYW wrote the manuscript; PZ, YZ and JJJ contributed to the review and editing; JJJ had primary responsibility for final content. All authors have approved the final version of the article.

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Correspondence to Yu Zhang or Jingjing Jiao.

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Chen, J., Wu, S., Wu, Y. et al. Long-term dietary DHA intervention prevents telomere attrition and lipid disturbance in telomerase-deficient male mice. Eur J Nutr 62, 1867–1878 (2023). https://doi.org/10.1007/s00394-023-03120-0

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  • DOI: https://doi.org/10.1007/s00394-023-03120-0

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