A randomized clinical trial involving obese individuals highlights the significance of dietary interventions in improving mitochondrial functions and the metabolic profile of monocytes, which are key aspects for controlling chronic inflammation in obesity. The trial report is published in the journal Clinical Nutrition . Randomized Control Trial: Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial .
Image Credit: Lightspring / Shutterstock Background Various dietary interventions, including calorie restriction, intermittent fasting, and ketogenic diet, have gained immense popularity for improving metabolic profiles and promoting body weight loss in obese or overweight individuals. Being the main source of cellular energy, mitochondria play a vital role in detecting and integrating environmental signals to induce adaptive cellular responses related to energy utilization. Mitochondrial dysfunction in obese individuals has been found to be associated with various chronic diseases.
Mitochondrial dysfunction in monocytes during obesity is known to contribute to low-grade chronic inflammation, a major hallmark of obesity. Recent evidence indicates that monocytes positively regulate fatty acid oxidation to reduce inflammatory responses in low-glucose environments. This suggests that dietary restrictions may influence monocyte bioenergetics.
In this randomized controlled clinical trial, scientists have investigated the effects of calorie restriction, intermittent fasting, a ketogenic diet, and an ad libitum (unrestricted) habitual diet on mitochondrial function in monocytes and its modulation by gut microbiota. Study design 44 obese individuals participated in this trial. For one month, they were randomly assigned to one of the four dietary intervention groups: calorie restriction, intermittent fasting, a ketogenic diet, or an ad libitum habitual diet.
Related Stories Tinnitus linked to obesity and body composition in men, study finds Accurate adiposity measurements key to tackling obesity-related diseases, study finds Feline gut microbes shed light on obesity treatment for humans The participants subsequently received rifaximin, a non-absorbable antibiotic, and continued with the assigned diet for another month. Rifaximin was used to evaluate gut microbiota's role in modulating dietary interventions' effects on mitochondrial function in monocytes. The trial included four follow-up visits, wherein mitochondrial function (oxygen consumption rate) in monocytes, anthropometric and biochemical parameters in serum samples, and gut microbiota composition in fecal samples were measured.
Important observations The study found a significant induction in the maximal respiration oxygen consumption rate in monocytes isolated from participants who underwent calorie restriction, intermittent fasting, or a ketogenic diet intervention, as compared to monocytes isolated from participants who consumed ad libitum habitual diet. This improvement in mitochondrial function was associated with a reduction in monocyte dependence on glycolysis for participants from the intermittent fasting and ketogenic diet groups. A significant induction in the gut microbiota diversity was observed in response to both dietary intervention and rifaximin in the intermittent fasting and ketogenic diet groups.
The dietary intervention and rifaximin collectively enriched the abundance of Phascolarctobacterium faecium in the calorie restriction group and Ruminococcus bromii in the calorie restriction and ketogenic diet groups and reduced the abundance of lipopolysaccharide (LPS)-producing bacteria in the calorie restriction, intermittent fasting, and ketogenic diet groups, as compared to that in the ad libitum habitual diet group. The correlation analysis between the tested variables identified serum LPS as a potential mediator of the changes observed in monocyte bioenergetics and gut microbiota composition. Specifically, significant inverse correlations of serum LPS concentration were observed with the maximal respiration oxygen consumption rate, bioenergetic health index, and the bacterium Phascolarctobacterium faecium (enriched abundance in the calorie restriction group).
In contrast, significant positive correlations of serum LPS concentration were observed with body mass index (BMI), compensatory glycolysis, and the bacterium Bacteroides eggertii . Enrichment of these variables was observed in the study population before dietary interventions, and these three variables were also enriched in the ad libitum habitual diet group. These observations collectively indicate that the modulation of the gut microbiota by dietary interventions and rifaximin impacts the phenotype and bioenergetic profile of the participants in the monocyte population, highlighting the potential role of LPS as a modulator of the observed effects.
A significant reduction in LPS-mediated intracellular signaling was observed in monocytes isolated from participants in the three dietary intervention groups. A significant reduction in body weight and visceral fat was also observed in these participants. Study significance The study finds that dietary interventions, including calorie restriction, intermittent fasting, and ketogenic diet, can improve body composition and mitochondrial bioenergetic health of monocytes in obese adults.
The study demonstrates that these dietary interventions shifted monocyte dependence from glycolysis to mitochondrial respiration. Apart from increasing mitochondrial function in monocytes, these interventions have induced positive changes in the gut microbiota composition. The study also proposes a potential mechanism explaining that the observed improvement in mitochondrial function due to dietary interventions is associated with a reduction in serum LPS and LPS-mediated intracellular signaling in monocytes.
Given the study findings, scientists suggest that evaluating mitochondrial function in monocytes could be used as an indicator of metabolic and inflammatory status, with potential applications in future clinical trials. Martha Guevara-Cruz. 2024.
Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial. Clinical Nutrition. https://www.
sciencedirect.com/science/article/pii/S0261561424002280.
