Dietary wolfberry upregulates carotenoid metabolic genes and enhances mitochondrial biogenesis in the retina of db/db diabetic mice

Abstract

Scope Our aim was to investigate whether dietary wolfberry altered carotenoid metabolic gene expression and enhanced mitochondrial biogenesis in the retina of diabetic mice. Methods and Results Six-week-old male db/db and wild type mice were fed the control or wolfberry diets for 8 weeks. At study termination, liver and retinal tissues were collected for analysis by transmission electron microscopy, real-time PCR, immunoprecipitation, Western blot, and HPLC. Wolfberry elevated zeaxanthin and lutein levels in the liver and retinal tissues and stimulated expression of retinal scavenger receptor class B type I, glutathione S-transferase Pi 1, and β,β-carotene 9’,10’-oxygenase 2, and induced activation and nuclear enrichment of retinal AMP-activated protein kinase α2 (AMPKα2). Furthermore, wolfberry attenuated hypoxia and mitochondrial stress as demonstrated by declined expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, and heat shock protein 60. Wolfberry enhanced retinal mitochondrial biogenesis in diabetic retinas as demonstrated by reversed mitochondrial dispersion in the retinal pigment epithelium, increased mitochondrial copy number, elevated citrate synthase activity, and up-regulated expression of peroxisome proliferator-activated receptor γ co-activator 1 α, nuclear respiratory factor 1, and mitochondrial transcription factor A. Conclusion Consumption of dietary wolfberry could be beneficial to retinoprotection through reversal of mitochondrial function in diabetic mice.

Lack of β, β‐carotene‐9′, 10′‐oxygenase 2 leads to hepatic mitochondrial dysfunction and cellular oxidative stress in mice

“…Further, the loss of BCO2 protein expression is associated with the development of anemia in zebrafish, though the anemia results not from impaired erythropoiesis, but instead from increased apoptosis of erythrocyte precursors (24). BCO2 expression is also significantly reduced in obese and diabetic mice (25, 26) . Accordingly, increased intake of a high-fat diet rich in carotenoids increase the expression of BCO2 protein and was associated with increased insulin sensitivity and attenuation of fatty liver in obese C57BL/6J mice (25).…”

“…BCO2 expression is also significantly reduced in obese and diabetic mice (25, 26) . Accordingly, increased intake of a high-fat diet rich in carotenoids increase the expression of BCO2 protein and was associated with increased insulin sensitivity and attenuation of fatty liver in obese C57BL/6J mice (25). Collectively, these findings indicate that BCO2 likely plays roles other than just as a carotenoid cleavage enzyme in mammals.…”

Inactivity of human β,β-carotene-9′,10′-dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment

“…Highaffinity binding proteins might drive this process. Mice and humans express a zeaxanthin-binding protein, the pi isoform of glutathione S-transferase (GSTP1), abundantly in the retina, yet only the human retina naturally contains zeaxanthin and meso-zeaxanthin (11,12). Thus, other biochemical mechanisms underlying accumulation of the human macular pigment need to be considered.…”

Hypercholesterolemia-induced ocular disorder: Ameliorating role of phytotherapy

“…Dietary administration of Wolfberry to diabetic mice was found to enhance retinal mitochondrial biogenesis especially in retinal pigmented epithelium [129].…”