Adiponectin and inflammation: Consensus and controversy

Role and regulation of adiponectin (APN) in metabolic versus autoimmune/chronic inflammatory disease. A variety of factors, including proinflammatory cytokines like TNF-α and IL-6, endothelial reticulum stress, and adipocyte hypertrophy have been demonstrated to inhibit APN production from adipocytes in the context of metabolic diseases such as T2D, CVD, and the metabolic syndrome (A). Possible (although not demonstrated) factors also influencing APN production during metabolic disease include, among others, increased adipocyte apoptosis and positive energy balance. A combination of the aforementioned conditions leads to low APN levels, which tend to perpetuate the state of low-grade chronic inflammation typical of metabolic disease. On the background of metabolic disease, APN levels are negatively correlated with markers of inflammation, such as CRP and IL-6, as well as with indices of insulin resistance and CVD. In contrast, during autoimmune/chronic inflammatory conditions such as T1D, RA, SLE, inflammatory bowel disease, and CF (B), an unknown range of factors, possibly including a tendency toward negative energy balance, leads to high levels of APN, either locally or systemically. These high levels of APN are positively rather than negatively correlated with markers of inflammation. The correlation between APN and insulin resistance or CVD in the context of autoimmune/chronic inflammatory diseases is still not completely clear. Furthermore, the issue of whether these high APN levels exert proinflammatory or anti-inflammatory effects remains open. ER, Endoplasmic reticulum.