Vitamin A deficiency results in dysregulation of lipid efflux pathway in rat kidney

Abstract

The mechanisms of action of vitamin A deficiency (VAD) on lipid metabolism in the rat kidney were investigated in adult female rats and their offspring. The rats were randomized into three groups: (1) control, in which the mother and offspring received a normal diet (4000 retinol IU/kg diet) for 8 weeks; (2) VAD group, in which the mothers and offspring received a VAD diet (400 retinol IU/kg diet) for 8 weeks; (3) vitamin A-refed group, in which a group of pups on a VAD diet for 8 weeks received a complete diet (6500 retinol IU/kg diet) for 15 days. The lipid metabolism of the offsprings' kidneys and its relation to the expression of apolipoprotein B100 (Apo-B100), liver X receptor alpha (LXRalpha), and retinoid X receptor-alpha/beta (RXRalpha/beta) mRNA was analyzed. VAD was found to alter renal lipid metabolism and its immune environment due to the expression of Apo-B100. Compared with the control, VAD rats had significantly higher levels of transforming growth factor-beta 1 and lower levels of ABCA1, a key gene involved in cholesterol efflux and tissue lipid homeostasis. The expression of LXRalpha and RXRalpha/beta mRNA also decreased in the VAD rat kidney. Vitamin A refeeding reversed all of the changes. Lipid metabolism involved in renal reverse cholesterol transport may be mediated by decreasing the signaling through the ABCA1 cholesterol efflux pathway, which is significantly modified in kidneys of vitamin A-deficient rats.

Vitamin A Deficiency and the Lung

“…Moreover, TGF-β1, via an integration of the Smad3 and STAT3 signalling pathways stimulates the connective tissue growth factor (CTGF), a central mediator of ECM production. In agreement, increased levels of TGF-β1 have been found in VAD tissues such as kidney, lung and aorta [ 32 , 123 , 186 , 188 , 189 , 190 , 191 , 192 , 193 ].…”

Vitamin A Deficiency and Alterations in the Extracellular Matrix

“…It has also been suggested that prenatal exposure to VAD may be a factor that contributes disproportionately to rising kidney disease incidence in disadvantaged populations [ 97 , 98 ]. It has also been found that VAD induces significant alterations in renal lipid metabolism and immune status, may contribute to the development of idiopathic kidney stones and may worsen renal diseases such as pyelonephritis [ 99 , 100 , 101 ]. The beneficial effect that retinoids have on several renal disorders, and their antifibrotic and cytoprotective effect on different types of renal cells [ 91 , 102 ], have also been demonstrated, which supports the importance of vitamin A for proper kidney development and for maintaining its integrity and function.…”

“…All these processes potentially lead to ECM overproduction. Increased TGF-β1 levels have been found in VAD tissues, such as kidney [ 101 ], lung [ 138 ], and aorta [ 173 ]. Therefore, signaling by this profibrotic factor can also mediate in ECM modifications.…”

Effect of Nutritional Status and Changes in Protein Intake on Renal Function

“…In developing countries, vitamin A deficiency is still a serious and widespread public health problem among pregnant women and children. Vitamin A also has an effect on energy metabolism, adipocyte differentiation, and lipid metabolism in different organs [109], including the kidney [110]. Animal studies have shown that mild vitamin A deficiency leads to inborn nephron deficit in the rat [108].…”