Stanislas Veillet

Quinoa Extract Enriched in 20‐Hydroxyecdysone Protects Mice From Diet‐Induced Obesity and Modulates Adipokines Expression

Besides their well‐known effect in the molting control in insects, ecdysteroids are steroid hormones that display potential pharmacologic and metabolic properties in mammals. The most common ecdysteroid, 20‐hydroxyecdysone (20E) is found in many plants such as quinoa. The aim of the present study was to investigate the ability of quinoa extract (Q) enriched in 20E supplementation to prevent the onset of diet‐induced obesity and to regulate the expression of adipocyte‐specific genes in mice. Mice were fed a standard low‐fat (LF) or a high‐fat (HF) diet with or without supplementation by 20E‐enriched Q or pure 20E for 3 weeks. Supplementation with Q reduced adipose tissue development in HF mice without modification of their body weight gain. This adipose tissue‐specific effect was mainly associated with a reduced adipocyte size and a decrease in the expression of several genes involved in lipid storage, including lipoprotein lipase and phosphoenolpyruvate carboxykinase. Furthermore, Q‐treated mice exhibited marked attenuation of mRNA levels of several inflammation markers (monocyte chemotactic protein‐1, CD68) and insulin resistance (osteopontin, plasminogen activator inhibitor‐1 (PAI‐1)) as compared to HF mice. Q supplementation also reversed the effects of HF‐induced downregulation of the uncoupling protein(s) (UCP(s)) mRNA levels in muscle. Similar results were obtained in mice fed a HF diet supplemented with similar amounts of pure 20E, suggesting that the latter accounted for most of the Q effects. Our study indicates that Q has an antiobesity activity in vivo and could be used as a nutritional supplement for the prevention and treatment of obesity and obesity‐associated disorders.

Quinoa extract enriched in 20-hydroxyecdysone affects energy homeostasis and intestinal fat absorption in mice fed a high-fat diet

In a previous study, we have demonstrated that a supplementation of a high-fat diet with a quinoa extract enriched in 20-hydroxyecdysone (QE) or pure 20-hydroxyecdysone (20E) could prevent the development of obesity. In line with the anti-obesity effect of QE, we used indirect calorimetry to examine the effect of dietary QE and 20E in high-fat fed mice on different components of energy metabolism. Mice were fed a high-fat (HF) diet with or without supplementation by QE or pure 20E for 3 weeks. As compared to mice maintained on a low-fat diet, HF feeding resulted in a marked physiological shift in energy homeostasis, associating a decrease in global energy expenditure (EE) and an increase in lipid utilization as assessed by the lower respiratory quotient (RQ). Supplementation with 20E increased energy expenditure while food intake and activity were not affected. Furthermore QE and 20E promoted a higher rate of glucose oxidation leading to an increased RQ value. In QE and 20E-treated HFD fed mice, there was an increase in fecal lipid excretion without any change in stool amount. Our study indicates that anti-obesity effect of QE can be explained by a global increase in energy expenditure, a shift in glucose metabolism towards oxidation to the detriment of lipogenesis and a decrease in dietary lipid absorption leading to reduced dietary lipid storage in adipose tissue.

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

The accumulation of N-retinylidene-N-retinylethanolamine (A2E, a toxic by-product of the visual pigment cycle) in the retinal pigment epithelium (RPE) is a major cause of visual impairment in the elderly. Photooxidation of A2E results in retinal pigment epithelium degeneration followed by that of associated photoreceptors. Present treatments rely on nutrient supplementation with antioxidants. 9’-cis-Norbixin (a natural diapocarotenoid, 97% purity) was prepared from Bixa orellana seeds. It was first evaluated in primary cultures of porcine retinal pigment epithelium cells challenged with A2E and illuminated with blue light, and it provided an improved photo-protection as compared with lutein or zeaxanthin. In Abca4-/- Rdh8-/- mice (a model of dry AMD), intravitreally-injected norbixin maintained the electroretinogram and protected photoreceptors against light damage. In a standard rat blue-light model of photodamage, norbixin was at least equally as active as phenyl-N-tert-butylnitrone, a free radical spin-trap. Chronic experiments performed with Abca4-/- Rdh8-/- mice treated orally for 3 months with norbixin showed a reduced A2E accumulation in the retina. Norbixin appears promising for developing an oral treatment of macular degeneration. A drug candidate (BIO201) with 9’-cis-norbixin as the active principle ingredient is under development, and its potential will be assessed in a forthcoming clinical trial.