Dietary Curcumin Systemically Maintains Insulin Homeostasis in Diet-Induced Aged Obese Mice via Liver-Pancreas-Brain Axis

Abstract Objectives Aging is a condition in which we gradually lose the ability to maintain homeostasis due to dysfunction. There continues to be a knowledge gap in implicating how dietary intervention affects the mechanisms delaying or preventing aging-related chronic diseases. Although curcumin (CUR), a natural antioxidant, shows the putative therapeutic properties such as reinstating insulin homeostasis in obese mice, an aging-associated mechanism in which CUR regulates insulin levels largely remains unclear. Thus, the objective of this study is to determine effects of CUR on anti-aging under obese condition mediated by maintaining insulin homeostasis via cross-talk among liver, pancreas and brain. Methods We examine how dietary CUR improves insulin clearance and maintains a proper range of circulating insulin level in the aged diet-induced obesity (DIO) mouse model. Old male C57BL/6J mice were fed a normal chow diet (NCD) or a NCD containing 0.4% (w/w) curcumin (NCD + CUR), a high fat/high sugar diet (HFHSD) or a HFHSD + CUR (N = 7–9 per group) for 16 weeks. Results Old male C57BL/6J mice were fed a normal chow diet (NCD) or a NCD containing 0.4% (w/w) curcumin (NCD + CUR), a high fat/high sugar diet (HFHSD) or a HFHSD + CUR (N = 7–9 per group) for 16 weeks. Mice given HFHSD + CUR had reduced body weight gain (4.7 ± 1.8 vs 7.8 ± 1.6g) and had lower blood insulin levels (2.24 ± 0.3 vs. 1.53 ± 0.3 ng/ml) under fasting conditions compared to mice on HFHSD alone, resulting from significantly improved insulin clearance via upregulation of hepatic insulin-degrading enzyme (IDE) and circulating IDE levels in serum. On the other hand, the expression of IDE gene in hypothalamus was significantly lower in HFHSD + CUR mice (1.3 folds) than HFHSD animals. Obesity induces hyperglycemic condition in brain by higher IDE expression to excessively break down insulin. We also observed significantly smaller islets of Langerhans (4.53 ± 0.72 vs 7.90 ± 0.34 a.u.) in HFSD + CUR fed mice and increased glucagon contents compared to HFS fed mice, indicating less secretion of insulin in pancreas under obese condition. Conclusions The conclusion of this study is that curcumin is a potent, natural therapeutic agent that can systemically regulate insulin levels in a multifaceted manner to protect against insulin resistance in aged mice. Funding Sources Intramural Research Program of NIAThe OTTOGI HAM TAIHO Foundation