Research Paper Volume 14, Issue 1 pp 225—239

Dietary curcumin restores insulin homeostasis in diet-induced obese aged mice

Su-Jeong Lee1, , Prabha Chandrasekran2, , Caio Henrique Mazucanti2, , Jennifer F. O’Connell2, , Josephine M. Egan2, , Yoo Kim1, ,

  • 1 Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA
  • 2 Laboratory of Clinical Investigation, National Institute on Aging (NIA), Baltimore, MD 21224, USA

Received: November 8, 2021       Accepted: December 29, 2021       Published: January 11, 2022
How to Cite

Copyright: © 2022 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Although aging is a physiological process to which all organisms are subject, the presence of obesity and type 2 diabetes accelerates biological aging. Recent studies have demonstrated the causal relationships between dietary interventions suppressing obesity and type 2 diabetes and delaying the onset of age-related endocrine changes. Curcumin, a natural antioxidant, has putative therapeutic properties such as improving insulin sensitivity in obese mice. However, how curcumin contributes to maintaining insulin homeostasis in aged organisms largely remains unclear. Thus, the objective of this study is to examine the pleiotropic effect of dietary curcumin on insulin homeostasis in a diet-induced obese (DIO) aged mouse model. Aged (18-20 months old) male mice given a high-fat high-sugar diet supplemented with 0.4% (w/w) curcumin (equivalent to 2 g/day for a 60 kg adult) displayed a different metabolic phenotype compared to mice given a high-fat high-sugar diet alone. Furthermore, curcumin supplementation altered hepatic gene expression profiling, especially insulin signaling and senescence pathways. We then mechanistically investigated how curcumin functions to fine-tune insulin sensitivity. We found that curcumin supplementation increased hepatic insulin-degrading enzyme (IDE) expression levels and preserved islet integrity, both outcomes that are beneficial to preserving good health with age. Our findings suggest that the multifaceted therapeutic potential of curcumin can be used as a protective agent for age-induced metabolic diseases.


CUR: Curcumin; DIO: Diet-induced obese; IDE: Insulin degrading enzyme; T2D: Type 2 diabetes, NCD: Normal chow diet; HFHSD: High-fat high-sugar diet; RNAseq: RNA sequencing; FDR: False discovery rate; DEGs: Differentially expressed genes; GO: Gene Ontology; TRs: Transcription regulators; MODY: Maturity-onset diabetes of the young; FPI: Fasting plasma insulin; ITT: Insulin tolerance test; AUC: Area under the curve.