Vitamin A signaling and homeostasis in obesity, diabetes, and metabolic disorders

Abstract

Much evidence has accumulated in the literature over the last fifteen years that indicates vitamin A has a role in metabolic disease prevention and causation. This literature proposes that vitamin A can affect obesity development and the development of obesity-related diseases including insulin resistance, type 2 diabetes, hepatic steatosis and steatohepatitis, and cardiovascular disease. Retinoic acid, the transcriptionally active form of vitamin A, accounts for many of the reported associations. However, a number of proteins involved in vitamin A metabolism, including retinolbinding protein 4 (RBP4) and aldehyde dehydrogenase 1A1 (ALDH1A1, alternatively known as retinaldehyde dehydrogenase 1 or RALDH1), have also been identified as being associated with metabolic disease. Some of the reported effects of these vitamin A-related proteins are proposed to be independent of their roles in assuring normal retinoic acid homeostasis. This review will consider both human observational data as well as published data from molecular studies undertaken in rodent models and in cells in culture. The primary focus of the review will be on the effects that vitamin A per se and proteins involved in vitamin A metabolism have on adipocytes, adipose tissue biology, and adipose-related disease, as well as on early stage liver disease, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

Serum retinol‐binding protein 4 as a predictor of cardiovascular events in elderly patients with chronic heart failure

“…RBP4 is mainly secreted by liver and adipose tissue, and elevated circulating RBP4 levels have been linked to diabetes, obesity, and metabolic disorders . In the present study, we also found that serum RBP4 levels were increased in patients with diabetes.…”

Decay in Retinoic Acid Signaling in Varied Models of Alzheimer’s Disease and In-Vitro Test of Novel Retinoic Acid Receptor Ligands (RAR-Ms) to Regulate Protective Genes

“…Particularly intriguing is the correlation of decreasing RBP4 in the CSF with progression of normal to mild cognitive impairment to AD, suggesting a movement of RBP4 between brain compartments with disease, although this study was with a small patient pool [86]. Changes in RBP4 may be part of the metabolic disorder linked with AD [87] and the inconsistent change between mouse models at 3 months in RBP4 tran-script suggests that this may not be an early change in disease.…”

“…For instance, the change in RALDH2 may, like CYP26A1 and CYP26B1, be a result of feedback regulation of the RA signaling system, or alternatively may be a response to inflammation. Changes in RBP4, STRA6 and CRBP1, associated with vitamin A's role in metabolic disease [87] may be linked with the metabolic abnormalities that occur in AD [119].…”

The Effect of Vitamin Supplementation on Subclinical Atherosclerosis in Patients without Manifest Cardiovascular Diseases: Never-ending Hope or Underestimated Effect?

“…The processing of vitamin A in the intestine after dietary intake is similar with triglycerides and cholesterol, but once absorbed, the metabolism, as well as its storage, is unique. Vitamin A is essential for mediating various physiological processes in the human body, some of them related to cholesterol and triglycerides metabolism, contributing to pathogenesis of metabolic diseases when dysregulated [123].…”