Nuclear Receptor RORα/γ: Exciting Modulators in Metabolic Syndrome and Related Disorders

Abstract

Under the influences of modern lifestyle, metabolic syndromes (MetS), including insulin resistance, obesity, and fatty liver, featuring a worldwide chronic disease, greatly raise the risk of type 2 diabetes, heart disease, and stroke. However, its pathogenesis is still unclear, and there are limited drugs with strong clinical efficacy and specificity. Given the close connection between impaired lipid metabolism and MetS onset, modulating the lipid metabolic genes may provide potential prospects in the development of MetS therapeutics. Nuclear receptors are such druggable transcription factors that translate physiological signals into gene regulation via DNA binding upon ligand activation. Recent studies reveal vital functions of the NRs retinoic acid's receptor-related orphan receptors (RORs), including RORα and RORγ, in the gene regulation in lipid metabolism and MetS. This review focuses on the latest developments in their actions on MetS and related metabolic disorders, which would benefit future clinically therapeutic applications.

Retinoic acids and nuclear receptor signaling in liver development: Pathogenic roles in liver diseases

“…71 Retinoic acid's receptor-related orphan receptors (ROR) exhibits widespread distribution in various body tissues, influencing essential processes like inflammatory responses, lipid metabolism, and neural tissue formation. 72,73 The imbalance in inflammatory response and lipid metabolism control plays a crucial role in determining the rate of liver fibrosis development. ROR regulates the expression of target genes involved in lipid metabolism, thereby promoting lipid metabolism stabilization, making it a potential key factor in preventing liver fibrosis.…”

“…Retinoic acid’s receptor‐related orphan receptors (ROR) exhibits widespread distribution in various body tissues, influencing essential processes like inflammatory responses, lipid metabolism, and neural tissue formation 72,73 . The imbalance in inflammatory response and lipid metabolism control plays a crucial role in determining the rate of liver fibrosis development.…”

Light Pollution and Oxidative Stress: Effects on Retina and Human Health

“…Despite these effects, the anti-proliferative properties of blue light may be leveraged for treating certain dermatological conditions, including acne, psoriasis, and precancerous lesions [ 39 , 152 ]. Blue light therapy has shown promising results in acne management [ 40 , 153 ], and positive outcomes have been noted in treatments with topical retinoids for mild skin conditions, such as psoriasis [ 130 , 131 , 132 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 ].…”

“…Additionally, they can serve as agonists or antagonists for retinoic acid or retinoid-X receptors, which are involved in regulating gene transcription impacting embryonic development, tissue homeostasis, metabolism, and cellular differentiation [ 132 , 159 ]. Dysregulation of these receptors has been associated with a variety of conditions, including cancer, autoimmune diseases, metabolic disorders, and inflammatory diseases [ 132 , 159 , 160 , 161 ]. Moreover, blue LED light has been observed to significantly enhance hair growth in patients with androgenetic alopecia [ 41 , 162 ].…”