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

New Findings What is the central question of this study? Previously, we reported that chronic feeding of a vitamin A‐enriched diet to euglycaemic obese rats (WNIN/Ob) ameliorated obesity. Does this diet exert similar effects even with a different genetic background, i.e. obese rats of the WNIN/GR‐Ob strain with impaired glucose tolerance? What is the main finding and its importance? Vitamin A‐enriched diet aggravated weight gain and adiposity/obesity in both lean and glucose‐intolerant obese rats of the WNIN/GR‐Ob strain. Therefore, the role of genetic factors and their regulation by nutrients in determining health and disease conditions assumes greater significance in experimental and clinical research. Vitamin A and its metabolites are key regulators of the development of adipose tissue and its associated metabolic complications. Here, we tested, in a glucose‐intolerant obese rat model (the WNIN/GR‐Ob stain), whether feeding a vitamin A‐enriched diet alters adiposity and its associated changes. For this purpose, 30‐week‐old male lean and obese rats were divided into two groups and received either stock diet or vitamin A‐enriched diet [2.6 or 129 mg vitamin A (kg diet)−1, respectively] for 14 weeks. At the end, feeding of the vitamin A‐enriched diet resulted in increased body weight gain/obesity and retroperitoneal white adipose tissue (RPWAT) in both lean and obese rats of the WNIN/GR‐Ob strain, when compared with their respective control animals receiving stock diet, without affecting food intake. An improvement in hypertriglyceridaemia and circulatory non‐esterified fatty acid levels and unaltered hepatic fatty acid oxidative and triglyceride secretory pathway proteins with vitamin A‐enriched diet feeding are suggestive of enhanced hepatic clearance of circulatory lipids, resulting in increased hepatic triglyceride accumulation. Transcriptional analysis of RPWAT showed that feeding the vitamin A‐enriched diet augmented the expression of adipogenic/adipose tissue‐specific genes; peroxisome proliferator‐activated receptor‐γ, stearoyl CoA desaturase 1, retinol saturase, leptin and lipoprotein lipase and vitamin A metabolic pathway genes; retinoic acid receptors, retinoid X receptors and cytochrome P450 26B1. Besides, RPWAT–lipoprotein lipase‐mediated clearance of triglyceride could also have contributed to increased adiposity and improved hypertriglyceridaemia. In conclusion, chronic feeding of vitamin A‐enriched diet induces weight gain and adiposity in