One week very low calorie diet fasting activates myeloid cell inflammasome responses to stimuli of the inborn immune system in people with type 2 diabetes

Subclinical inflammation induced by obesity, unhealthy diet and sedentary behavior is closely linked to the risks of cardiovascular disease and type 2 diabetes. Weight loss is recommended to resolve inflammation which involves the inflammasome in the inborn immune system.

We investigated the responses to inflammasome-TLR stimuli ex vivo in circulating immune cells before and after one week and 12 weeks of very low calorie diet fasting with 600/800 kcal/day in 20 obese women/men with T2DM. RNAseq of monocytes was used to assess changes of gene expression. A highly significant increase of the cytokines IL-1ß, IL-6, IL-10 and IFNy was observed after 1 week followed by a significant decrease after 12 weeks of continued fasting. The chemokines MIP1a, MIP1beta, MCP-1 and IP-10 which direct immune cell trafficking followed a similar although less pronounced pattern. TLR4 (LPS) and TLR8 (resiquimod) inducers, but much less TLR2 (Peptidoglycan) and TLR7 (Imiquimod) stimuli, were most potent. RNAseq in monocytes revealed variable changes of gene expression which did not fully match the immune responses. Notably, levels of glucose and insulin were markedly reduced in parallel indicating a separation of inflammation from insulin resistance. Short term fasting may rather induce than attenuate inflammation which offers an explanation for the unfavorable consequences of weight cycling. Whether long term fasting persistently reduces inflammasome hyperactivation remains to be answered.

Publication History

Article published online:
02 May 2023