Vitamin A supplementation in early life affects later response to an obesogenic diet in rats

Abstract

OBJECTIVE:To assess the influence of supplementation with a moderate dose of vitamin A in early life on adipose tissue development and the response to an obesogenic diet later in life. METHODS: During the suckling period, rat pups received a daily oral dose of retinyl palmitate corresponding to three times the vitamin A ingested daily from maternal milk. Control rats received the vehicle (olive oil). Short-term effects of treatment on gene expression and morphology of white adipose tissue (WAT) were analyzed in animals on the day after weaning (day 21). To study long-term effects, control and vitamin A-treated rats were fed, after weaning, a normal fat or a high-fat (HF) diet for 16 weeks. RESULTS: WAT of vitamin A-treated young rats (day 21) was enriched in small adipocytes with a reduced expression of adipogenic markers (peroxisome proliferator-activated receptor g and lipoprotein lipase) and an increased cell proliferation potential as indicated by increased expression of proliferating cell nuclear antigen. Increased retinoic acid (RA)-induced transcriptional responses were present in the tissues of vitamin A-treated young rats (day 21) including WAT. Vitamin A-treated rats developed higher adiposity than control rats on a HF diet as indicated by body composition analysis and increased WAT depot mass, adipocyte diameter, WAT DNA content, leptinemia and adipose leptin gene expression. Excess adiposity gain in vitamin A-treated rats developed in the absence of changes in body weight and was attributable to excess adipocyte hyperplasia. No differences in adiposity were observed between vitamin A-treated rats and control rats on a normal fat diet. Total retinol levels in WAT of vitamin A-treated rats were elevated at weaning (day 21) and normalized by day 135 of age. CONCLUSION: Vitamin A intake in the early stages of postnatal life favors subsequent HF diet-induced adiposity gain through mechanisms that may relate to changes in adipose tissue development, likely mediated by RA.

Chronic vitamin A‐enriched diet feeding induces body weight gain and adiposity in lean and glucose‐intolerant obese rats of WNIN/GR‐Ob strain

“…Notably, more than three decades ago, Murray & Russell, 1980 demonstrated the inhibitory effect of retinoic acid on adipogenesis in 3T3-L1 pre-adipocytes. Subsequently, many studies have shown a similar inhibitory effect of retinoids on adipogenesis/adiposity, using both in vitro and in vivo models, perhaps through different mechanisms (Arana et al 2008;Redonnet et al 2008;Landrier et al 2012;Brun et al 2013;Granados et al 2013). Thus, the suggestion is that the regulation of adiposity/obesity by vitamin A and its metabolites depends on species, sex, age, duration and dosage.…”

“…; Granados et al . ). Thus, the suggestion is that the regulation of adiposity/obesity by vitamin A and its metabolites depends on species, sex, age, duration and dosage.…”

Tissue- and sex-specific effects of β-carotene 15,15′ oxygenase (BCO1) on retinoid and lipid metabolism in adult and developing mice

“…Furthermore, a number of laboratories have provided evidence that BCO1 can be placed at a critical intersection of carotenoid, retinoid and lipid metabolism in various tissues [15, 16, 31, 35, 36]. Our laboratory first proposed that BCO1, in addition to its main function as an enzyme that metabolizes β-carotene and apocarotenoids, can influence ester formation from various substrates, such as retinol, cholesterol and diacylglycerols in the mouse embryo at mid-gestation [16].…”

Dietary Antioxidant and Oxidative Stress: Interaction between Vitamins and Genetics

“…The animals supplemented with vitamin A developed greater adiposity hyperplasia compared to the control group after the intervention fat diet, detected by analysis of body composition (increased mass of subcutaneous adipose tissue), diameter of adipocytes, presence of leptin and increased expression of LEP gene in adipose tissue. In this study, it was concluded that, in animal models, vitamin A supplementation in the early stages of postnatal life favored fat diet induced adiposity, through mechanisms that may be related to changes in adipose tissue development [45].…”