Obesity-Induced TNFα and IL-6 Signaling: The Missing Link between Obesity and Inflammation-Driven Liver and Colorectal Cancers.

Obesity promotes the development of numerous cancers, such as liver and colorectal cancers, which is at least partly due to obesity-induced, chronic, low-grade inflammation. In particular, the recruitment and activation of immune cell subsets in the white adipose tissue systemically increase proinflammatory cytokines, such as tumor necrosis factor α (TNFα) and interleukin-6 (IL-6). These proinflammatory cytokines not only impair insulin action in metabolic tissues, but also favor cancer development.

Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment.

Colorectal cancer (CRC) is one of the most lethal cancers worldwide in which the vast majority of cases exhibit little genetic risk but are associated with a sedentary lifestyle and obesity. Although the mechanisms underlying CRC and colitis-associated colorectal cancer (CAC) remain unclear, we hypothesised that obesity-induced inflammation predisposes to CAC development. Here, we show that diet-induced obesity accelerates chemically-induced CAC in mice via increased inflammation and immune cell recruitment.

Binding of the IclR-type regulator HutR in the histidine utilization (hut) gene cluster of the human pathogen Corynebacterium resistens DSM 45100.

The genome of the human pathogen Corynebacterium resistens DSM 45100 is equipped with a histidine utilization (hut) gene cluster encoding a four-step pathway for the catabolism of l-histidine and a transcriptional regulator of the IclR superfamily, now named HutR. The utilization of l-histidine might be relevant for the growth of C. resistens in its natural habitat, probably the histidine-rich inguinal and perineal areas of the human body.