Hostname: page-component-65f69f4695-pm9fr Total loading time: 0 Render date: 2025-06-27T02:08:03.720Z Has data issue: false hasContentIssue false
  • English
  • Français

Curcumin ameliorates the effects of high-fat diet-induced obesity via activating the DNA repair response

Published online by Cambridge University Press:  02 June 2025

Jinkyung Cho Open the ORCID record for Jinkyung Cho [Opens in a new window]  and
Eunmi Park
Jinkyung Cho
Affiliation:
College of Sport Science, Sungkyunkwan University, Suwon, Republic of Korea Diabetes Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, USA
Eunmi Park*
Affiliation:
Diabetes Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, USA Department of Food and Nutrition, Hannam University, Daejeon, Republic of Korea
*
Corresponding author: Eunmi Park; Email: eunmi_park@hnu.kr
Get access Rights & Permissions [Opens in a new window]

Abstract

Curcumin, a natural bioactive compound, is known to exert therapeutic effects on cancer and dysplasia. However, less is known about its effects on DNA damage and repair in obesity. Therefore, this study was to examine the novel role of curcumin in regulating DNA repair signalling using a high-fat diet (HFD)-induced obesity in mice. Male C57BL/6 mice were fed either a 60 % HFD or standard chow with curcumin (2·5 g/kg diet) for 8 weeks. We observed that curcumin alleviated weight gain, preserved glucose balance and enhanced liver fat accumulation and lipid profile in mice with obesity induced by an HFD. Curcumin enhanced the adipocyte-derived mesenchymal stem cell (ADMSC) population (Sca-1 + CD45-) and expression of phosphorylated checkpoint kinase1 (pCHK1), a DNA repair gene, in adipocytes isolated from adipose tissues of HFD-induced obesity in mice. Moreover, in human preadipocytes, treatment with 10 μM curcumin effectively reduced the mRNA levels of IL6 and CCL2 in a dose-dependent manner, while treatment with 100 μM H2O2 together with curcumin upregulated the levels of pCHK2 and total CHK2 protein and reduced level of γH2AX, a biomarker of DNA damage. In addition, curcumin inhibits preadipocyte-to-adipocyte differentiation. In conclusion, our data demonstrated that curcumin reduced the pro-inflammatory response and DNA damage in adipocytes, controlling weight gain in mice with HFD-induced obesity.

Keywords

CurcuminDNA repairAdipocytesObesityHigh fat diet

Information

Type
Research Article
Information
British Journal of Nutrition , First View , pp. 1 - 10
Check for updates
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of the Nutrition Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Lee, MJ, Wu, Y & Fried, SK (2013) Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Aspects Med 34, 1–11.Google Scholar
Crewe, C, An, YA & Scherer, PE (2017) The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. J Clin Invest 127, 74–82.Google Scholar
Chandel, NS, Maltepe, E, Goldwasser, E, et al. (1998) Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci U S A 95, 11715–11720.Google Scholar
Lumeng, CN, Bodzin, JL & Saltiel, AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117, 175–184.Google Scholar
Saltiel, AR & Olefsky, JM (2017) Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest 127, 1–4.Google Scholar
McLaughlin, T, Ackerman, SE, Shen, L, et al. (2017) Role of innate and adaptive immunity in obesity-associated metabolic disease. J Clin Invest 127, 5–13.Google Scholar
Al-Aubaidy, HA & Jelinek, HF (2011) Oxidative DNA damage and obesity in type 2 diabetes mellitus. Eur J Endocrinol 164, 899–904.Google Scholar
Bar, RS, Levis, WR, Rechler, MM, et al. (1978) Extreme insulin resistance in ataxia telangiectasia: defect in affinity of insulin receptors. N Engl J Med 298, 1164–1171.Google Scholar
Lin, Q, Lee, YJ & Yun, Z (2006) Differentiation arrest by hypoxia. J Biol Chem 281, 30678–30683.Google Scholar
Ching, JK, Spears, LD, Armon, JL, et al. (2013) Impaired insulin-stimulated glucose transport in ATM-deficient mouse skeletal muscle. Appl Physiol Nutr Metab 38, 589–596.Google Scholar
Zhou, BB & Elledge, SJ (2000) The DNA damage response: putting checkpoints in perspective. Nature 408, 433–439.Google Scholar
Lans, H, Hoeijmakers, JHJ, Vermeulen, W, et al. (2019) The DNA damage response to transcription stress. Nat Rev Mol Cell Biol 20, 766–784.Google Scholar
Takagi, M, Uno, H, Nishi, R, et al. (2015) ATM regulates adipocyte differentiation and contributes to glucose homeostasis. Cell Rep 10, 957–967.Google Scholar
Choi, YE & Park, E (2015) Curcumin enhances poly (ADP-ribose) polymerase inhibitor sensitivity to chemotherapy in breast cancer cells. J Nutr Biochem 26, 1442–1447.Google Scholar
Weisberg, SP, Leibel, R & Tortoriello, DV (2008) Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinol 149, 3549–3558.Google Scholar
Feng, D, Zou, J, Su, D, et al. (2019) Curcumin prevents high-fat diet-induced hepatic steatosis in ApoE-/- mice by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF-κB inflammation. Nutr Metab (Lond) 16, 79.Google Scholar
Hasanzadeh, S, Read, MI, Bland, AR, et al. (2020) Curcumin: an inflammasome silencer. Pharmacol Res 159, 104921.Google Scholar
Mokgalaboni, K, Ntamo, Y, Ziqubu, K, et al. (2021) Curcumin supplementation improves biomarkers of oxidative stress and inflammation in conditions of obesity, type 2 diabetes and NAFLD: updating the status of clinical evidence. Food Funct 12, 12235–12249.Google Scholar
Hassan, MH, Awadalla, EA, Abd El-Kader, AEM, et al. (2022) Antitoxic effects of curcumin against obesity-induced multi-organs’ biochemical and histopathological abnormalities in an animal model. Evid Based Complement Alternat 2022, 9707278.Google Scholar
Shao, W, Yu, Z, Chiang, Y, et al. (2012) Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS One 7, e28784.Google Scholar
Li, S, You, J, Wang, Z, et al. (2021) Curcumin alleviates high-fat diet-induced hepatic steatosis and obesity in association with modulation of gut microbiota in mice. Food Res Int 143, 110270.Google Scholar
Kleiner, DE, Brunt, EM, Natta, MV, et al. (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41, 1313–1321.Google Scholar
Folch, J, Lees, M & Sloane Stanley, GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226, 497–509.Google Scholar
Cho, J & Park, E (2020) Ferulic acid maintains the self-renewal capacity of embryo stem cells and adipose-derived mesenchymal stem cells in high fat diet-induced obese mice. J Nutr Biochem 77, 108327.Google Scholar
Acharya, JD & Ghaskadbi, SS (2013) Protective effect of Pterostilbene against free radical mediated oxidative damage. BMC Complement Altern Med 13, 238.Google Scholar
Ferguson, BS, Nam, H & Morrison, RF (2016) Curcumin inhibits 3T3-L1 preadipocyte proliferation by mechanisms involving post-transcriptional p27 regulation. Biochem Biophys Rep 5, 16–21.Google Scholar
Jiménez-Flores, LM, López-Briones, S, Macías-Cervantes, MH, et al. (2014) A PPARγ, NF-κB and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver. Molecules 19, 8289–8302.Google Scholar
Xu, H, Barnes, GT, Yang, Q, et al. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112, 1821–1830.Google Scholar
Guilherme, A, Virbasius, JV, Puri, V, et al. (2008) Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 9, 367–377.Google Scholar
Wang, T, Yan, R, Xu, X, et al. (2019) Curcumin represses adipogenic differentiation of human bone marrow mesenchymal stem cells via inhibiting kruppel-like factor 15 expression. Acta Histochem 121, 253–259.Google Scholar
Ong, WK, Tan, CS, Chan, KL, et al. (2014) Identification of specific cell-surface markers of adipose-derived stem cells from subcutaneous and visceral fat depots. Stem Cell Rep 2, 171–179.Google Scholar
Pincu, Y, Huntsman, HD, Zou, K, et al. (2016) Diet-induced obesity regulates adipose-resident stromal cell quantity and extracellular matrix gene expression. Stem Cell Res 17, 181–190.Google Scholar
Uccelli, A, Moretta, L & Pistoia, V (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8, 726–736.Google Scholar
Ravindranath, V & Chandrasekhara, N (1980) Absorption and tissue distribution of curcumin in rats. Toxicology 16, 259–265.Google Scholar
Xue, M, Cheng, Y, Xu, L, et al. (2017) Study of the intestinal absorption characteristics of curcumin in vivo and in vitro . J Appl Pharm 9, 3.Google Scholar
Sharm, RA, Euden, SA, Platton, SL, et al. (2004) Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10, 6847–6854.Google Scholar
Supplementary material: File

Cho and Park supplementary material 1

Cho and Park supplementary material
Download Cho and Park supplementary material 1(File)
File 540 KB
Supplementary material: File

Cho and Park supplementary material 2

Cho and Park supplementary material
Download Cho and Park supplementary material 2(File)
File 514.9 KB
Supplementary material: File

Cho and Park supplementary material 3

Cho and Park supplementary material
Download Cho and Park supplementary material 3(File)
File 24.6 KB
Supplementary material: File

Cho and Park supplementary material 4

Cho and Park supplementary material
Download Cho and Park supplementary material 4(File)
File 486.9 KB