Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects.
Level 4 - case-series / case-control
Small single-arm before-after human intervention combined with ex vivo and in vitro laboratory experiments.
PubMed 26529255 · doi:10.1172/JCI83260
What was done
Nineteen healthy volunteers underwent a 24-hour fast followed by a fixed-calorie meal, with blood collected during fasted and refed states to measure NLRP3 inflammasome activation. An additional cohort of 8 healthy volunteers was evaluated to assess the effects of the sirtuin activator nicotinamide riboside. Ex vivo human leukocytes and a human macrophage cell line were used to evaluate SIRT3 manipulation and mitochondrial reactive oxygen species production.
What was found
The abstract reports directional findings without numeric values or effect sizes. NLRP3 inflammasome activation was lower in the fasted state compared with the refed state in human subjects. In macrophage culture, SIRT3 depletion elevated NLRP3 activation alongside increased mitochondrial reactive oxygen species, whereas genetic and pharmacologic SIRT3 activation blunted NLRP3 activity in cultured cells and leukocytes from refed individuals.
Why it matters
This study provides mechanistic evidence in humans linking acute fasting to suppressed NLRP3 inflammasome activity via SIRT3-dependent mitochondrial regulation.
Limits
The human component used small sample sizes (19 and 8 participants) of healthy volunteers in single-arm protocols without a parallel control group. The protocol evaluated only an acute 24-hour fast, leaving longer-term effects and clinical efficacy in patients with inflammasome-linked diseases untested. No quantitative estimates or confidence intervals are reported in the abstract.
Cited by
- supports A 24-hour fast in 19 healthy volunteers suppressed gene expression of the NLRP3 inflammasome, which reversed upon refeeding.