In a recent study published within the Journal of Biological Chemistry, researchers explored the association between high-fat diets and vitamin A aldehyde dysregulation, which leads to bisretinoid accumulation in eyes, resulting in opposed outcomes for retinal pigment epithelial and photoreceptor cells.
Study: A High Fat Weight loss program Fosters Elevated Bisretinoids. Image Credit: Lucky Business / Shutterstock
Vitamin A aldehyde adducts called bisretinoids are formed when retinaldehyde reacts with the photoreceptor outer segment lipid and accumulates naturally with age in human eyes. Bisretinoids have properties that cause opposed outcomes, comparable to photosensitivity, with the tendency to supply reactive oxygen forms comparable to singlet oxygen and superoxide anion. These reactive oxygen species further react with bisretinoids, resulting in the discharge of molecular fragments with dicarbonyl and aldehyde.
Modulation through visual cycle kinetics can control the speed of bisretinoid accumulation. These include limiting vitamin A delivery to retinal pigment epithelial cells, mutations that reduce the activity of retinoid isomerohydrolase RPE65, and deficiencies of assorted visual cycle proteins comparable to lecithin retinol acyltransferase and 11-cis retinol dehydrogenase. Moreover, race, gender, and smoking have shown associations with increased accumulation of bisretinoids. On condition that high-fat diets increase the degrees of vitamin A within the serum, it can be crucial to look at the associations between diets wealthy in fats and the buildup of bisretinoids.
In regards to the study
In the current study, the researchers used two mice models of obesity — one with high-fat diet-induced obesity (black C57BL/6J mice) and the opposite with leptin deficiency-induced obesity (ob/ob)— to check the buildup of bisretinoids. Leptin is a hormone produced within the adipose tissue that regulated food intake and energy expenditure. The identical mouse model that was fed a regular food plan as a substitute of a high-fat food plan was used because the control.
High performance liquid chromatography (HPLC) and ultra-performance liquid chromatography (UPLC) were used to discover peaks for pyridinium bisretinoid conjugates A2E (synthesized from vitamin A aldehyde and ethanolamine), isoA2E, A2-dihydropyridine-phosphatidylethanolamine (A2-DHP-PE), and A2-glycerophosphoethanolamine (A2GPE).
To account for the degradation of bisretinoids through photodegradation, comparisons were also made using albino mice that were fed the usual and the high-fat diets. Extremely old black C57BL/6J mice ate up a high-fat food plan were also studied to find out the impact of age on the association between a high-fat food plan and bisretinoid accumulation. Moreover, the degrees of retinol-binding protein 4, retinoids, and phosphatidylethanolamine were measured.
Bisretinoid levels were also non-invasively measured through spectrophotometry using confocal fluorescence scanning laser ophthalmoscopy to quantify the short wavelength fundus autofluorescence. Moreover, the outer nuclear layer thickness was measured after the mice were sacrificed, and the eyes were enucleated to find out the viability of the photoreceptor cells.
The outcomes indicated that within the black C57BL/6J and albino mice models that were fed high-fat diets, the extent of bisretinoids quantified using chromatography was higher than that in mice that were fed the usual food plan. Fundus autofluorescence measurements also indicated that the bisretinoid levels were elevated within the mice ate up a high-fat food plan.
Plasma levels of retinol-binding protein 4 and vitamin A were also higher within the mice ate up a high-fat food plan as in comparison with the mice ate up a regular food plan. Nevertheless, the vitamin A levels within the ocular tissue weren’t comparatively higher. Moreover, phosphatidylethanolamine levels were also elevated within the high-fat diet-fed mice than within the mice ate up the control food plan.
Within the mice model deficient in leptin, although the plasma levels of retinol-binding protein 4 were high, the bisretinoid levels within the retina had not increased. Nevertheless, the decrease in outer nuclear layer thickness indicated that the viability of the photoreceptor cells was reduced within the ob/ob mice as in comparison with the wild-type mice.
The researchers imagine that a high-fat food plan may end up in bisretinoid accumulation through two potential mechanisms — either through the rise within the bisretinoid fluorophores comprising the retina lipofuscin or by increasing the phosphatidylethanolamine levels within the photoreceptor cells. Other studies have also reported alterations as a result of a high-fat food plan within the relative proportions of linoleic acid and α-linoleic acid, the precursors of omega-3 and omega-6 polyunsaturated fatty acids, respectively, within the retina.
To summarize, the study examined the association between high-fat diet-induced and leptin deficiency-induced obesity and the buildup of bisretinoids within the eyes using mice models of obesity. The findings suggested that bisretinoid accumulation is related to a high-fat food plan and as a result of a rise in vitamin A delivery to the visual cycle.