Retinoic acid-related orphan receptors ? and ?: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity.

ABSTRACT: Retinoic acid-related orphan receptors ROR? and ROR? play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. ROR?-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in ROR?-deficient mice is related to the reduced expression of several genes regulating lipid synthesis, transport, and storage. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in ROR?-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in ROR? also protects against diet-induced insulin resistance by a mechanism that appears different from that in ROR? deficiency. Recent studies indicated that RORs provide an important link between the circadian clock machinery and its regulation of metabolic genes and metabolic syndrome. As ligand-dependent transcription factors, RORs may provide novel therapeutic targets in the management of obesity and associated metabolic diseases, including hepatosteatosis, adipose tissue-associated inflammation, and insulin resistance.

SUBMITTER: Jetten AM 

PROVIDER: S-EPMC3555121 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature