Vitamin A Supplementation during Suckling and Postweaning Periods Attenuates the Adverse Metabolic Effects of Maternal High-Fat Diet Consumption in Sprague-Dawley Rats

Abstract

Background Vitamin A (VA) is demonstrated to be a regulator of adipose tissue (AT) development in adult obese models. However, little is known about the effect of VA on obesity-associated developmental and metabolic conditions in early life. Objective To assess the effects of dietary VA supplementation during suckling and post-weaning periods on the adiposity and metabolic health of neonatal and weanling rats from mothers consuming a high fat diet (HFD). Methods Pregnant Sprague-Dawley rats were fed a normal fat diet (NFD; 25% fat; n = 2) or an HFD (50% fat; n = 2) both with 2.6 mg/kg of VA. Upon delivery, half of rat mothers were switched to diets with supplemented VA at 129 mg/kg, while the other half remained at 2.6 mg/kg of VA. Four groups of rat pups were designated as NFD, NFD + VA, HFD, and HFD + VA, respectively. At postnatal day 14 (P14), P25, and P35, pups (n = 4 or 3/group) were euthanized. Body weight (BW), visceral white AT (WAT) mass, brown AT (BAT) mass, uncoupling protein 1 mRNA expression in BAT, serum glucose, lipids, adipokines, and inflammatory biomarkers, as well as serum and AT redox status were assessed. Results Rat pups in the HFD group exhibited significantly higher BW, WAT mass, and serum glucose and leptin but reduced BAT mass compared with the NFD group. Without affecting the dietary intake, supplementing the HFD with VA significantly reduced the BW and WAT mass of pups but increased the BAT mass, significantly lowered the systemic and WAT oxidative stress, and modulated serum adipokines and lipids to some extent. Conclusion VA supplementation during suckling and post-weaning periods attenuated metabolic perturbations caused by excessive fat intake. Supplementing maternal or infant obesogenic diets with VA or establishing a higher recommended dietary allowance of VA for specific populations should be studied further for managing overweight/obesity in early life.

Retinoic acid promotes tissue vitamin A status and modulates adipose tissue metabolism of neonatal rats exposed to maternal high-fat diet-induced obesity

“…The changes may partially be the result of increased WAT in HFD pups and reduced tissue mass by the RA treatment. The findings on serum leptin are consistent with our previous study, in which maternal dietary VA supplementation was also found to decrease the enhanced serum leptin concentration in HFD pups (30) . Previous studies in adult rodent models also showed that chronic dietary VA supplementation reduced serum leptin as well as leptin gene expression in WAT (58,59) .…”

“…In adult rodents, RA was shown to inhibit adipogenesis and stimulate angiogenesis and apoptosis in white adipose tissue (WAT), and to increase the adaptive thermogenesis of brown adipose tissue (BAT) via regulating the expression of uncoupling proteins (UCPs) (26)(27)(28)(29) . Our previous study indicated that supplementing the maternal diet with VA during lactation significantly reduced the adiposity and modulated serum adipokines and lipids in neonatal and weanling rats from dams consuming a high fat diet (HFD) (30) . However, no study has evaluated the effect of direct RA administration on the AT development of neonates affected by maternal diet-induced obesity.…”

Developmental programming of peripheral diseases in offspring exposed to maternal obesity during pregnancy

“…This suggests that any adverse outcomes of the in utero environment cannot be negated by the postweaning diet. Notably, supplementation of the diet with vitamin A in rats augmented metabolic dysfunction in offspring exposed to an obesogenic diet in utero (108). This suggests that some aspects of the postweaning diet may be beneficial in reducing the programming potential of a maternal obesogenic diet in pregnancy.…”

Adipose Tissue Immunometabolism and Apoptotic Cell Clearance

“…Engulfment of apoptotic cells by macrophages leads to the synthesis of retinoids, which, in part, are responsible for some transcriptional changes of the M2-activation program and for the sustained phagocytosis capacity of macrophages [ 68 , 69 , 71 , 72 ]. Retinoids accumulate in the adipocytes and can inhibit adipocyte differentiation, reduce fat accumulation, and promote the expression of uncoupling protein 1 (UCP1) and the development of BAT-like adipocytes in WAT depots in mouse [ 73 , 74 , 75 , 76 , 77 ]. Expression of UCP1 confers BAT-like properties to WAT adipocytes, including thermogenic potential—a process termed adipocyte browning or beige adipogenesis [ 78 ].…”