Nutrient‐Gene Interactions in Mitochondrial Function: Vitamin A Needs Are Increased in BHE/Cdb Rats

Abstract

SummaryThe BHE/Cdb rat has a maternally inherited mutation in the ATPase 6 mitochondrial gene that associates with impaired oxidative phosphorylation (OXPHOS) and glucose intolerance. A longevity study revealed that feeding an egg-rich (vitamin A-rich) diet delayed the onset of impaired glucose tolerance. Two experiments were conducted to test the hypothesis that BHE/Cdb rats require more dietary vitamin A than normal rats. Experiment 1 was a dose-response study examining OXPHOS in BHE/Cdb rats fed one of six levels of vitamin A. In experiment 2 BHE/Cdb and Sprague-Dawley rats were used. The rats were depleted of retinol stores, then repleted with 4 or 12 IU vitamin A/g diet. Vitamin A status was assessed in depleted, never depleted, and depleted/repleted rats. OXPHOS was optimized at 4 IU/g diet for the Sprague-Dawley rats and 12 IU/g diet for the BHE/Cdb rats. These results suggested that the criteria for vitamin intake adequacy in the BHE/Cdb rats is the optimization of mitochondrial OXPHOS. Using this criteria, we conclude that diabetes-prone BHE/Cdb rats require more dietary vitamin A than normal rats. IUBMB Life, 53: 289-294, 2002

Mutated ATP synthase induces oxidative stress and impaired insulin secretion in β‐cells of female BHE/cdb rats

“…In addition, a reduction in oxygen consumption is predicted, again promoting increased oxygen radicals. A reduced respiratory control ratio is reported in the liver of BHE/cdb rats [8], consistent with increased free radical production. Pancreatic β-cells have low expression of antioxidant enzymes [9] and are highly susceptible to oxidative stress.…”

Endogenous Retinoids in the Pathogenesis of Alopecia Areata

“…Vitamin A deficiency leads to follicular hyperkeratosis and rupture in humans and rodents (Girard et al ., 2006; Wolbach and Howe, 1925). In rodents, vitamin A deficiency also leads to a thin hair coat that is frequently seen, but rarely reported (Anzano et al ., 1979) (unpublished observation; Everts and Berdanier, 2002). The results from these studies suggest precise RA levels are needed for optimal hair follicle function.…”

Endogenous retinoids in the hair follicle and sebaceous gland

“…Follicular hyperkeratosis was also seen in vitamin A deficient humans [2]. Vitamin A deficiency in rodents also leads to a thin hair coat that is frequently seen, but rarely reported [3] (unpublished observation from [4]). Hair loss (alopecia) is a consistent finding during vitamin A toxicity [5–7].…”