(P03-078-23) Zeaxanthin Improves Lipid and Glucose Metabolism in Type 2 Diabetic Mice

Objectives: As a lipophilic antioxidant, zeaxanthin is protective against diabetes-associated retinal metabolic dysfunction, oxidative stress, and damage. This study aimed to investigate zeaxanthin’s protective role on lipid and glucose metabolism in type 2 diabetic mice.

Methods: Four-week-old male and female C57BL/6J wild type (WT) and type 2 diabetic (db/db) mice were assigned into four groups: 1) WT fed an AIN93M control diet (WT + C), 2) WT fed an AIN93M supplemented with 0.02 % zeaxanthin (WT + Z), 3) db/db + C, 4) db/db + Z for four weeks. Mice were fed ad libitum and had free access to water throughout the study.  Body weight (BW), fasting blood glucose (FBG), and food intake were monitored on a weekly basis. At the end of the dietary treatments, animals were euthanized, and blood, liver, and epididymal white adipose tissue (eWAT) were collected. qPCR and immunoblotting were used to evaluate expression levels of genes and proteins related to lipid and glucose metabolism. Serum non-esterified fatty acids (NEFA) were measured using a clinical chemistry analyzer. Data were analyzed by two-way ANOVA and student’s t-test, with P< 0.05 considered statistically significant. N=10-15 per group.

Results: Db/db mice fed a control diet were diabetic at 8 weeks of age. Compared to the control diet, zeaxanthin administration significantly decreased FBG levels, food intake, BW gain, and eWAT mass in db/db mice but not WT. In db/db mice, zeaxanthin administration markedly downregulated peroxisome proliferator-activated receptor alpha transcription and elevated AMP-activated protein kinase alpha (AMPK-α) protein levels in the liver. Furthermore, zeaxanthin administration significantly decreased expression levels of fatty acid translocase and fatty acid transport 1, while increasing expression of long-chain acyl-CoA dehydrogenase and forkhead box protein O1 genes in the liver of db/db mice.

Conclusions: Our results suggest that zeaxanthin may improve impaired lipid metabolism and blood glucose control in diabetic mice potentially by enhancing hepatic AMPK activation and long-chain fatty acid oxidation.

Funding Sources: USDA NIFA