Fasting regulates inflammation in inflammatory bowel diseases
The mechanisms by which reduced caloric intake modulates inflammation are poorly understood. Here we show that short-term fasting reduced monocyte metabolic and inflammatory activity.
Caloric excess, frequent in the Western world, has been linked to systemic low-grade chronic inflammation (Lumeng and Saltiel, 2011) and is thought to contribute to numerous diseases including metabolic syndrome (MetS), non-alcoholic fatty liver diseases (NAFLD), type 2 diabetes mellitus (T2DM), atherosclerosis, cardiovascular disease (CVD), and other related co-morbidities (Haslam and James, 2005). Accordingly, the recent diet westernization of developing countries has been associated with an increased prevalence of inflammatory or autoimmune disorders (Manzel et al., 2014).
In contrast, hypocaloric diets or fasting regimens are associated with improved outcomes of metabolic, autoimmune, and inflammatory diseases in humans, including NAFLD (Kani et al., 2017), T2DM (Zubrzycki et al., 2018), CVD (Wei et al., 2017), multiple sclerosis (Choi et al., 2016), rheumatoid arthritis (Kjeldsen-Kragh et al., 1991, Sköldstam et al., 1979), asthma (Johnson et al., 2007) and psoriasis (Jensen et al., 2016), and have been shown to prolong lifespan (Fontana et al., 2010, Picca et al., 2017). However, the molecular mechanisms by which reduced calorie intake or fasting modulate systemic inflammation remain poorly understood.
Our study identified a drastic effect of short-term and intermittent fasting on the blood and tissue monocyte pool and revealed the role of dietary intake in the control of metabolic and inflammatory activity of monocytes and their egress to the blood circulation.
Monocytes are important producers of pro-inflammatory cytokines and play a critical role in the induction and maintenance of inflammation. Therefore, it is conceivable that modulation of peripheral monocyte load in blood and tissues by repetitive short-term fasting or caloric restriction decreases susceptibility to pathological inflammatory disease. Indeed, circulating monocytes are increased in overweight and obese humans and caloric restriction has been shown to reduce peripheral pro-inflammatory cells leading to an overall improved inflammatory profile (Kani et al., 2017, Poitou et al., 2011).
Constant or intermittent reduced calorie intake improves inflammatory and autoimmune disease outcome. Importantly, our finding that pharmacological AMPK activation regardless of caloric intake was sufficient to regulate the blood monocyte pool suggests that targeting liver energy sensors could be an innovative strategy for the prevention and treatment of chronic inflammatory and autoimmune diseases without affecting antimicrobial immunity.
Read full research paper at https://www.cell.com/cell/fulltext/S0092-8674(19)30850-5