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.
