The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism

Abstract

Currently, two-thirds of American adults are overweight or obese. This high prevalence of overweight/obesity negatively affects the health of the population, as obese individuals tend to develop several chronic diseases, such as type 2 diabetes and cardiovascular diseases. Due to obesity's impact on health, medical costs, and longevity, the rise in the number of obese people has become a public health concern. Both genetic and environmental/dietary factors play a role in the development of metabolic diseases. Intuitively, it seems to be obvious to link over-nutrition to the development of obesity and other metabolic diseases. However, the underlying mechanisms are still unclear. Dietary nutrients not only provide energy derived from macronutrients, but also factors such as micronutrients with regulatory roles. How micronutrients, such as vitamin A (VA; retinol), regulate macronutrient homeostasis is still an ongoing research topic. As an essential micronutrient, VA plays a key role in the general health of an individual. This review summarizes recent research progress regarding VA's role in carbohydrate, lipid, and protein metabolism. Due to the large amount of information regarding VA functions, this review focusses on metabolism in metabolic active organs and tissues. Additionally, some perspectives for future studies will be provided.

Keywords: glucose metabolism; lipid metabolism; metabolic diseases; protein metabolism; vitamin A.

Figure 1

Schematic representation of vitamin A (VA) digestion, absorption, transport, and metabolism in the body. Dietary VA from plant and animal sources is digested in the intestinal lumen and absorbed by enterocytes via different mechanisms. Within the enterocytes, the dietary VA is converted into retinyl esters, which are packaged into chylomicrons for the secretion into the lymph and eventually enter the circulation. The lipoprotein lipase hydrolyzes triglycerides (TGs) on the chylomicrons to produce chylomicron remnants. The retinyl ester-containing chylomicron remnants are eventually taken up by hepatocytes, where the retinyl esters are again hydrolyzed into retinol. The released retinol can be transported to target cells and catabolized into retinal, retinoic acid (RA), or other metabolites. Excessive retinol is re-esterified into retinyl esters, which are stored in stellate cells. BB-REH, brush-border retinyl ester hydrolase; LRAT, lecithin:retinol acyltransferase; ARAT, acyl-CoA:retinol acyltransferase; RBP, retinol binding protein; RDH, retinol dehydrogenase; RALDH, retinal dehydrogenase; REH, retinol ester hydrolase; STRA6, stimulated by retinoic acid 6; RA, retinoic acid; RARE, retinoic acid responsive element; RAR, retinoic acid receptor; RXR, retinoid X receptor; TTR, transthyretin; PPAR, peroxisome proliferator-activated receptor; HNF4α, hepatocyte nuclear factor 4α; COUP-TFII, chicken ovalbumin up-stream transcription factor II.

Figure 2

Mechanism by which RA induces thermogenesis in adipocytes. Stepwise enzymatic reactions convert retinol into retinal, and then retinal into RA in the adipocytes. RA enters the nucleus, where it modulates the expression of UCP genes by activating the corresponding nuclear receptors in the promoters of the genes. Increased UCP proteins uncouple oxidative phosphorylation from ATP production. The reduced H⁺ gradient across the mitochondrial membranes leads to the increase of thermogenesis in the adipocytes. ROL, retinol; RBP, retinol binding protein; TTR, transthyretin; RAL, retinal; RDH, retinol dehydrogenase; RALDH, retinal dehydrogenase; RA, retinoic acid; RARE, retinoic acid responsive element; RAR, retinoic acid receptor; RXR, retinoid X receptor; UCP, uncoupling protein; PPAR, peroxisome proliferator activated receptor; HNF4α, hepatocyte nuclear factor 4α; COUP-TFII, chicken ovalbumin up-stream transcription factor II.