Abstract
Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. RORα-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in RORα-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 RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in RORγ also protects against diet-induced insulin resistance by a mechanism that appears different from that in RORα 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.
Highlights
In the past 50 years, the occurrence of obesity has greatly increased worldwide in both adults and children and has become a major health-care concern in many countries
Obesity leads to a systemic state of low-grade inflammation, involving adipose tissue, that is causally involved in the development of insulin resistance and other diseases
These investigations showed that RORαsg/sg mice are protected against age- and diet-induced obesity and the development of several obesity-linked pathologies, including adipose tissue-associated inflammation, hepatosteatosis, and insulin resistance (Kang et al, 2011; Lau et al, 2011)
Summary
In the past 50 years, the occurrence of obesity has greatly increased worldwide in both adults and children and has become a major health-care concern in many countries. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes.
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