are not entirely understood. Rev-erbα regulates the expression of liver apolipoproteins, sterol regulatory element binding protein, and the fatty acid elongase elovl3 through its repressional activity In addition, the silencing of Rev-erbα is associated with the reduction of fatty acid synthase, a key regulator of lipogenesis. Rev-erbα deficient mice exhibit dyslipidemia due to elevated triglyceride levels and Rev-erbα polymorphisms in humans have been associated with obesity. Rev-erbα also regulates adipogenesis of white and brown adipocytes. Rev-Erbα transcription is induced during the adipogenic process, and over-expression of Rev-erbα enhances adipogenesis. Researchers have proposed that Rev-erbα's role in adipocyte function may affect the timing of processes such as lipid storage and lipolysis, contributing to long term issues with BMI control. Rev-erbα also regulates bile acid metabolism by indirectly down-regulating Cyp7A1, which encodes the first and rate controlling enzyme of the major bile acid biosynthetic pathway. Rev-erbα plays both indirect and direct roles in glucose metabolism. BMAL1 heavily influences glucose production and glycogen synthesis, thus through the regulation of BMAL1, Rev-erbα indirectly regulates glucose synthesis. More directly, Rev-erbα’s expression in the pancreas regulates the function of α-cells and β-cells, which produce glucagon and insulin, respectively. Muscle and cartilage Rev-erbα plays a role in myogenesis through interaction with the transcription complex Nuclear Factor-T. It also represses the expression of genes involved in muscle cell differentiation and is expressed in a circadian manner in mouse skeletal muscle. Loss of Rev-erbα function reduces mitochondrial content and function, leading to an impaired exercise capacity. Over-expression leads to improvement. This protein has also been implicated in the integrity of cartilage. Out of all known nuclear receptors, Rev-erbα is the most highly expressed in osteoarthritic cartilage. One study found that in patients with osteoarthritis has reduced Rev-erbα levels compared to normal cartilage. Research on rheumatoid arthritis (RA) has implicated the potential for treatment with Rev-erbα agonists to RA patients due to their suppression of bone and cartilage destruction. Immune system Rev-erbα contributes to the inflammatory response in mammals. In mouse smooth muscle cells, the protein up-regulates expression of interleukin 6 (IL-6) and cyclooxygenase-2. In humans, it controls the lipopolysaccharide (LPS) induced endotoxic response through repressing toll-like receptor (TLR-4), which triggers the immune response to LPS. In the brain, Rev-erbα deletion causes a disruption in the oscillation of microglial activation and increases the expression of pro-inflammatory transcripts. Many immune and inflammatory proteins exhibit circadian oscillatory behavior, and research has shown