Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Basic Science Article
  • Published:

Prepuberty is a window period for curcumin to prevent obesity in postnatal overfed rats

Pediatric Research (2024)Cite this article

Abstract

Background

Overnutrition in early life increases the risk of obesity and metabolic diseases. We investigated the effects and the window period of a curcumin (CUR) diet on postnatal overfed rats.

Methods

Male rats aged 3 days were randomly divided into normal litters (NL, 10 pups/litter) and small litters (SL, 3 pups/litter). After weaning (Week 3, W3), NL rats were fed a normal diet (NL) and SL rats were fed a normal diet (SL) or 2% CUR diet from weaning (W3) (SL-CURW13), beginning of puberty (W6) (SL-CURW16), or end of puberty (W8) (SL-CURW18) for 10 weeks.

Results

Body weight, glucose intolerance and hyperlipidemia in the SL rats were higher than in the NL rats, especially after puberty. After the CUR intervention, SL-CURW13 and SL-CURW16 rats showed lower body weight gain, adipose tissue weight and mRNA level of C/EBPα in SAT, along with higher mRNA levels of β-catenin. There was no difference between SL and SL-CURW18 rats. Glucose tolerance, serum lipids and hepatic lipids recovered to normal in the SL-CURW13 rats, but only partially in the SL-CURW16 and SL-CURW18 rats.

Conclusion

Prepuberty is a window period for CUR intervention to improve programmed outcomes in postnatal overfed rats.

Impact

  • Overnutrition during the first 1000 days of life has persistent negative effects on metabolism. Strategies should be taken to prevent overnutrition in early life to reduce the risk of obesity and metabolic disease in later life.

  • A small-litter rat model was utilized to simulate early-life overnutrition in humans. We investigated the different effects and critical period for curcumin intervention on postnatal overfed rats.

  • Dietary curcumin intervention before puberty could effectively transform nutritional programming to reduce obesity and metabolic disorders caused by early-life overnutrition, and an earlier intervention might predict a better outcome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Dynamic changes of programmed outcomes in postnatal overfed rats
Fig. 2: Effects of curcumin intervention on body weight.
Fig. 3: Effects of curcumin intervention on glucose tolerance and biochemical parameters.
Fig. 4: Effects of curcumin intervention on adipose tissue weight and histology.
Fig. 5: Effect of curcumin intervention on hepatic lipids and histologic morphology.
Fig. 6: Expression levels of genes related to adipocyte proliferation and differentiation in SAT.

Similar content being viewed by others

Data availability

Data included in this manuscript are available upon request by contacting the corresponding author.

References

  1. Pan, X. F., Wang, L. & Pan, A. Epidemiology and Determinants of Obesity in China. Lancet Diabetes Endocrinol. 9, 373–392 (2021).

    Article  PubMed  Google Scholar 

  2. Jaacks, L. M. et al. The Obesity Transition: Stages of the Global Epidemic. Lancet Diabetes Endocrinol. 7, 231–240 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Di Cesare, M. et al. The Epidemiological Burden of Obesity in Childhood: A Worldwide Epidemic Requiring Urgent Action. BMC Med. 17, 212 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mameli, C., Mazzantini, S. & Zuccotti, G. V. Nutrition in the First 1000 Days: The Origin of Childhood Obesity. Int. J. Environ. Res. Public Health 13, 838 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Agosti, M., Tandoi, F., Morlacchi, L. & Bossi, A. Nutritional and Metabolic Programming during the First Thousand Days of Life. Pediatr. Med. Chir. 39, 157 (2017).

    Article  PubMed  Google Scholar 

  6. Draijer, L., Benninga, M. & Koot, B. Pediatric NAFLD: An Overview and Recent Developments in Diagnostics and Treatment. Expert Rev. Gastroenterol. Hepatol. 13, 447–461 (2019).

    Article  CAS  PubMed  Google Scholar 

  7. La Colla, A., Cámara, C. A., Campisano, S. & Chisari, A. N. Mitochondrial Dysfunction and Epigenetics Underlying the Link between Early-Life Nutrition and Non-Alcoholic Fatty Liver Disease. Nutr. Res. Rev. 362, 1–33 (2022).

    Google Scholar 

  8. Langley-Evans, S. C. Nutrition in Early Life and the Programming of Adult Disease: A Review. J. Hum. Nutr. Diet. 28, 1–14 (2015).

    Article  PubMed  Google Scholar 

  9. Xavier, J. L. P. et al. Litter Size Reduction Induces Metabolic and Histological Adjustments in Dams throughout Lactation with Early Effects on Offspring. Acad. Bras. Cienc. 91, e20170971 (2019).

    Article  Google Scholar 

  10. Parra-Vargas, M., Ramon-Krauel, M., Lerin, C. & Jimenez-Chillaron, J. C. Size Does Matter: Litter Size Strongly Determines Adult Metabolism in Rodents. Cell Metab. 32, 334–340 (2020).

    Article  CAS  PubMed  Google Scholar 

  11. Zhou, N., Du, S., Dai, Y., Yang, F. & Li, X. ω3pufas Improve Hepatic Steatosis in Postnatal Overfed Rats and HepG2 Cells by Inhibiting Acetyl-COA Carboxylase. Food Sci. Nutr. 9, 5153–5165 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhu, X. et al. Dietary Curcumin Supplementation Promotes Browning and Energy Expenditure in Postnatal Overfed Rats. Nutr. Metab. 18, 97 (2021).

    Article  CAS  Google Scholar 

  13. Du, S. et al. Curcumin Alleviates Hepatic Steatosis by Improving Mitochondrial Function in Postnatal Overfed Rats and Fatty L02 Cells through the SIRT3 Pathway. Food Funct. 13, 2155–2171 (2022).

    Article  CAS  PubMed  Google Scholar 

  14. Patel, S. S. et al. Cellular and Molecular Mechanisms of Curcumin in Prevention and Treatment of Disease. Crit. Rev. Food Sci. Nutr. 60, 887–939 (2020).

    Article  CAS  PubMed  Google Scholar 

  15. Jabczyk, M., Nowak, J., Hudzik, B. & Zubelewicz-Szkodzińska, B. Curcumin in Metabolic Health and Disease. Nutrients 13, 4440 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Abd El-Hameed, N. M., Abd El-Aleem, S. A., Khattab, M. A., Ali, A. H. & Mohammed, H. H. Curcumin Activation of Nuclear Factor E2-Related Factor 2 Gene (Nrf2): Prophylactic and Therapeutic Effect in Nonalcoholic Steatohepatitis (NASH). Life Sci. 285, 119983 (2021).

    Article  CAS  PubMed  Google Scholar 

  17. Hassan, M. H. et al. Antitoxic Effects of Curcumin against Obesity-Induced Multi-Organs’ Biochemical and Histopathological Abnormalities in an Animal Model. Evid. Based Complement Altern. Med. 2022, 9707278 (2022).

    Article  Google Scholar 

  18. Chen, Y. et al. Curcumin Prevents Obesity by Targeting TRAF4-Induced Ubiquitylation in M(6) A-Dependent Manner. EMBO Rep. 22, e52146 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hellmann, P. H. et al. The Effect of Curcumin on Hepatic Fat Content in Individuals with Obesity. Diabetes Obes. Metab. 24, 2192–2202 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vors, C. et al. Supplementation with Resveratrol and Curcumin Does Not Affect the Inflammatory Response to a High-Fat Meal in Older Adults with Abdominal Obesity: A Randomized, Placebo-Controlled Crossover Trial. J. Nutr. 148, 379–388 (2018).

    Article  PubMed  Google Scholar 

  21. Rahmani, S. et al. Treatment of Non-Alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-Controlled Trial. Phytother. Res. 30, 1540–1548 (2016).

    Article  CAS  PubMed  Google Scholar 

  22. Norris, S. A. et al. Nutrition in Adolescent Growth and Development. Lancet 399, 172–184 (2022).

    Article  PubMed  Google Scholar 

  23. Brown, T. et al. Interventions for Preventing Obesity in Children. Cochrane Database Syst. Rev. 7, Cd001871 (2019).

    PubMed  Google Scholar 

  24. Mintjens, S. et al. Cardiorespiratory Fitness in Childhood and Adolescence Affects Future Cardiovascular Risk Factors: A Systematic Review of Longitudinal Studies. Sports Med. 48, 2577–2605 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lee, J. H. et al. Heat-Killed Enterococcus Faecalis Prevents Adipogenesis and High Fat Diet-Induced Obesity by Inhibition of Lipid Accumulation through Inhibiting C/EBP-α and PPAR-γ in the Insulin Signaling Pathway. Nutrients 14, 1308 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Luo, J., Yu, Z., Tovar, J., Nilsson, A. & Xu, B. Critical Review on Anti-Obesity Effects of Phytochemicals through Wnt/β-Catenin Signaling Pathway. Pharm. Res. 184, 106461 (2022).

    Article  CAS  Google Scholar 

  27. Schneider, M. Adolescence as a Vulnerable Period to Alter Rodent Behavior. Cell Tissue Res. 354, 99–106 (2013).

    Article  CAS  PubMed  Google Scholar 

  28. Bolton, M. M. et al. Postnatal Alterations in GABAB Receptor Tone Produce Sensorimotor Gating Deficits and Protein Level Differences in Adulthood. Int J. Dev. Neurosci. 41, 17–27 (2015).

    Article  CAS  PubMed  Google Scholar 

  29. Koletzko, B. et al. Nutrition During Pregnancy, Lactation and Early Childhood and Its Implications for Maternal and Long-Term Child Health: The Early Nutrition Project Recommendations. Ann. Nutr. Metab. 74, 93–106 (2019).

    Article  CAS  PubMed  Google Scholar 

  30. Fall, C. H. D. & Kumaran, K. Metabolic Programming in Early Life in Humans. Philos. Trans. R. Soc. Lond. B Biol. Sci. 374, 20180123 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Haschke, F., Binder, C., Huber-Dangl, M. & Haiden, N. Early-Life Nutrition, Growth Trajectories, and Long-Term Outcome. Nestle Nutr. Inst. Workshop Ser. 90, 107–120 (2019).

    Article  PubMed  Google Scholar 

  32. Kerkhof, G. F. & Hokken-Koelega, A. C. Rate of Neonatal Weight Gain and Effects on Adult Metabolic Health. Nat. Rev. Endocrinol. 8, 689–692 (2012).

    Article  PubMed  Google Scholar 

  33. Tock, L. et al. Nonalcoholic Fatty Liver Disease Decrease in Obese Adolescents after Multidisciplinary Therapy. Eur. J. Gastroenterol. Hepatol. 18, 1241–1245 (2006).

    Article  PubMed  Google Scholar 

  34. Grønbæk, H. et al. Effect of a 10-Week Weight Loss Camp on Fatty Liver Disease and Insulin Sensitivity in Obese Danish Children. J. Pediatr. Gastroenterol. Nutr. 54, 223–228 (2012).

    Article  PubMed  Google Scholar 

  35. de Piano, A. et al. Metabolic and Nutritional Profile of Obese Adolescents with Nonalcoholic Fatty Liver Disease. J. Pediatr. Gastroenterol. Nutr. 44, 446–452 (2007).

    Article  PubMed  Google Scholar 

  36. Nowak, K. L. et al. Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with Autosomal Dominant Polycystic Kidney Disease: Design and Baseline Characteristics of Participants. Contemp. Clin. Trials Commun. 19, 100635 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Lewanda, A. F., Gallegos, M. F. & Summar, M. Patterns of Dietary Supplement Use in Children with Down Syndrome. J. Pediatr. 201, 100–105.e130 (2018).

    Article  PubMed  Google Scholar 

  38. Hanai, H. et al. Curcumin Maintenance Therapy for Ulcerative Colitis: Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial. Clin. Gastroenterol. Hepatol. 4, 1502–1506 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Heidari, Z., Daei, M., Boozari, M., Jamialahmadi, T. & Sahebkar, A. Curcumin Supplementation in Pediatric Patients: A Systematic Review of Current Clinical Evidence. Phytother. Res. 36, 1442–1458 (2022).

    Article  CAS  PubMed  Google Scholar 

  40. Saadati, S. et al. The Effects of Curcumin Supplementation on Liver Enzymes, Lipid Profile, Glucose Homeostasis, and Hepatic Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease. Eur. J. Clin. Nutr. 73, 441–449 (2019).

    Article  CAS  PubMed  Google Scholar 

  41. Hodaei, H., Adibian, M., Nikpayam, O., Hedayati, M. & Sohrab, G. The Effect of Curcumin Supplementation on Anthropometric Indices, Insulin Resistance and Oxidative Stress in Patients with Type 2 Diabetes: A Randomized, Double-Blind Clinical Trial. Diabetol. Metab. Syndr. 11, 41 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sahebkar, A. et al. Curcuminoids Modulate Pro-Oxidant-Antioxidant Balance but Not the Immune Response to Heat Shock Protein 27 and Oxidized LDL in Obese Individuals. Phytother. Res. 27, 1883–1888 (2013).

    Article  CAS  PubMed  Google Scholar 

  43. Saraf-Bank, S., Ahmadi, A., Paknahad, Z., Maracy, M. & Nourian, M. Effects of Curcumin on Cardiovascular Risk Factors in Obese and Overweight Adolescent Girls: A Randomized Clinical Trial. Sao Paulo Med. J. 137, 414–422 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Yan, H. et al. Ajuba Functions as a Co-Activator of C/EBPβ to Induce Expression of PPARγ and C/EBPα During Adipogenesis. Mol. Cell Endocrinol. 539, 111485 (2022).

    Article  CAS  PubMed  Google Scholar 

  45. Liu, M., Qin, J., Cong, J. & Yang, Y. Chlorogenic Acids Inhibit Adipogenesis: Implications of Wnt/β-Catenin Signaling Pathway. Int J. Endocrinol. 2021, 2215274 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Chen, N. & Wang, J. Wnt/β-Catenin Signaling and Obesity. Front. Physiol. 9, 792 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Harvey, I. et al. Glucocorticoid-Induced Metabolic Disturbances Are Exacerbated in Obese Male Mice. Endocrinology 159, 2275–2287 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hou, M. et al. Neonatal Overfeeding Induced by Small Litter Rearing Causes Altered Glucocorticoid Metabolism in Rats. PLoS One 6, e25726 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Yan, C. et al. Curcumin Regulates Endogenous and Exogenous Metabolism via Nrf2-FXR-LXR Pathway in NAFLD Mice. Biomed. Pharmacother. 105, 274–281 (2018).

    Article  CAS  PubMed  Google Scholar 

  50. Saadati, S. et al. Curcumin and Inflammation in Non-Alcoholic Fatty Liver Disease: A Randomized, Placebo Controlled Clinical Trial. BMC Gastroenterol. 19, 133 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Teixeira, D., Martins, C., Oliveira, G. & Soares, R. Metabolically Healthy Obesity in a Paediatric Obesity Clinic. J. Pediatr. Endocrinol. Metab. 35, 1147–1153 (2022).

    Article  CAS  PubMed  Google Scholar 

  52. Mathis, B. J., Tanaka, K. & Hiramatsu, Y. Factors of Obesity and Metabolically Healthy Obesity in Asia. Medicine 58, 1271 (2022).

    Google Scholar 

  53. Smith, G. I., Mittendorfer, B. & Klein, S. Metabolically Healthy Obesity: Facts and Fantasies. J. Clin. Invest 129, 3978–3989 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Li, S. et al. Curcumin Alleviates High-Fat Diet-Induced Hepatic Steatosis and Obesity in Association with Modulation of Gut Microbiota in Mice. Food Res. Int. 143, 110270 (2021).

    Article  CAS  PubMed  Google Scholar 

  55. Kindblom, J. M. et al. BMI Change during Puberty and the Risk of Heart Failure. J. Intern. Med. 283, 558–567 (2018).

    Article  CAS  PubMed  Google Scholar 

  56. Ohlsson, C., Bygdell, M., Nethander, M., Rosengren, A. & Kindblom, J. M. BMI Change During Puberty Is an Important Determinant of Adult Type 2 Diabetes Risk in Men. J. Clin. Endocrinol. Metab. 104, 1823–1832 (2019).

    Article  PubMed  Google Scholar 

  57. Suzuki, A. et al. Association between Puberty and Features of Nonalcoholic Fatty Liver Disease. Clin. Gastroenterol. Hepatol. 10, 786–794 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Jones, J. G. Hepatic Glucose and Lipid Metabolism. Diabetologia 59, 1098–1103 (2016).

    Article  CAS  PubMed  Google Scholar 

  59. Reinehr, T., Kleber, M., Lass, N. & Toschke, A. M. Body Mass Index Patterns over 5 Y in Obese Children Motivated to Participate in a 1-Y Lifestyle Intervention: Age as a Predictor of Long-Term Success. Am. J. Clin. Nutr. 91, 1165–1171 (2010).

    Article  CAS  PubMed  Google Scholar 

  60. Sangouni, A. A., Taghdir, M., Mirahmadi, J., Sepandi, M. & Parastouei, K. Effects of Curcumin and/or Coenzyme Q10 Supplementation on Metabolic Control in Subjects with Metabolic Syndrome: A Randomized Clinical Trial. Nutr. J. 21, 62 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by the National Natural Science Foundation of China (81773421) and the Innovation Team of Jiangsu Health (CXTDA2017035).

Author information

Authors and Affiliations

  1. Department of Child Health Care, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, Jiangsu, China

    Susu Du, Nan Zhou, Wen Zheng, Xiaolei Zhu, Ru Ling, Wei Zhou & Xiaonan Li

Authors
  1. Susu Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wen Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaolei Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ru Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaonan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Xiaonan Li designed the study. Susu Du, Nan Zhou and Wen Zheng performed the experiments. Susu Du analyzed the data and wrote the original draft. Xiaolei Zhu, Ru Ling and Wei Zhou reviewed the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Xiaonan Li.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

All animal studies were approved by the University Committee on Use and Care of Animals and were overseen by the Unit for Laboratory Animal Medicine of Nanjing Medical University (ID: 1904056-1).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Du, S., Zhou, N., Zheng, W. et al. Prepuberty is a window period for curcumin to prevent obesity in postnatal overfed rats. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03154-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41390-024-03154-y

Search

Advanced search

Quick links