Vitamin D and Systems Biology

Abstract

The biological actions of the vitamin D receptor (VDR) have been investigated intensively for over 100 years and has led to the identification of significant insights into the repertoire of its biological actions. These were initially established to be centered on the regulation of calcium transport in the colon and deposition in bone. Beyond these well-known calcemic roles, other roles have emerged in the regulation of cell differentiation processes and have an impact on metabolism. The purpose of the current review is to consider where applying systems biology (SB) approaches may begin to generate a more precise understanding of where the VDR is, and is not, biologically impactful. Two SB approaches have been developed and begun to reveal insight into VDR biological functions. In a top-down SB approach genome-wide scale data are statistically analyzed, and from which a role for the VDR emerges in terms of being a hub in a biological network. Such approaches have confirmed significant roles, for example, in myeloid differentiation and the control of inflammation and innate immunity. In a bottom-up SB approach, current biological understanding is built into a kinetic model which is then applied to existing biological data to explain the function and identify unknown behavior. To date, this has not been applied to the VDR, but has to the related ERα and identified previously unknown mechanisms of control. One arena where applying top-down and bottom-up SB approaches may be informative is in the setting of prostate cancer health disparities.

Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance

“…Vitamin D deficiency can lead to a decrease in β cell insulin secretion, exacerbating IR and increasing the risk of DM[ 28 ]. By binding to the receptor, vitamin D regulates the expression of immune- and apoptosis- related genes in pancreatic tissues, protecting islet β cells and weakening apoptosis[ 29 ]. In addition, vitamin D can affect insulin secretion and release by regulating intracellular calcium levels, and further improves insulin sensitivity by regulating insulin receptor expression and glucose transport sensitivity[ 30 ].…”

Editorial on Human Milk as a Biological System

“…Others advocate for mathematical or engineering perspectives, or “downstream” omics approaches, including genomics, transcriptomics, metabolomics, lipidomics, and proteomics (Amin et al, 2022), particularly useful for explanatory models of disorders and diseases. Typically, there are two approaches—a top down and a bottom-up—in systems biology (Hussain et al, 2022). The top-down approach uses omics type data and looks for hubs where interactions occur in biological networks for the area under study.…”

A Pleiotropic Nuclear Hormone Labelled Hundred Years Ago Vitamin D

“…This year we are celebrating 100 years of the naming of vitamin D, but the molecule is, in fact, more than one billion years old [ 1 ]. Nutrition Bulletin and Endocrine Connections are also honoring the centenary of vitamin D’s discovery, but with 21 original publications and review articles written by experts in the field, Nutrients represents the largest collection [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”