Dietary interventions such as calorie restriction, intermittent fasting, and ketogenic diets have gained popularity for improving metabolic health and aiding weight loss in individuals with obesity. Mitochondria, crucial for cellular energy production, play a pivotal role in responding to environmental signals and are implicated in metabolic dysregulation associated with obesity.
Mitochondrial dysfunction in monocytes during obesity contributes to chronic low-grade inflammation, a hallmark of the condition. Recent studies suggest that dietary restrictions may influence monocyte bioenergetics, potentially mitigating inflammation.
Study Design:
A randomized controlled clinical trial involved 44 obese participants randomly assigned to one of four dietary groups: calorie restriction, intermittent fasting, ketogenic diet, or ad libitum habitual diet for one month. Following this, participants received rifaximin, a non-absorbable antibiotic, to assess the role of gut microbiota in modulating dietary effects on mitochondrial function.
Participants underwent four follow-up visits to assess mitochondrial function in monocytes (oxygen consumption rate), anthropometric measures, serum biochemical parameters, and gut microbiota composition.
Key Findings:
Improved Mitochondrial Function: Calorie restriction, intermittent fasting, and ketogenic diet interventions significantly increased maximal respiratory oxygen consumption rate in monocytes compared to ad libitum habitual diet.
Shift in Monocyte Bioenergetics: Intermittent fasting and ketogenic diet groups showed reduced reliance on glycolysis, indicating enhanced mitochondrial function.
Gut Microbiota Changes: Intermittent fasting and ketogenic diet groups exhibited increased gut microbiota diversity. Rifaximin further enriched beneficial bacteria like Phascolarctobacterium faecium (in calorie restriction group) and Ruminococcus bromii (in calorie restriction and ketogenic diet groups), while reducing LPS-producing bacteria.
Serum LPS as a Mediator: Serum LPS levels correlated inversely with mitochondrial function and beneficial bacteria (e.g., Phascolarctobacterium faecium), and positively with BMI and glycolysis. Dietary interventions and rifaximin lowered LPS-mediated signaling in monocytes.
Clinical Significance: Dietary interventions improved body composition, reduced visceral fat, and enhanced mitochondrial bioenergetics in monocytes of obese adults. These findings suggest monocyte mitochondrial function as a potential indicator of metabolic and inflammatory status.
Conclusion:
This study underscores the therapeutic potential of dietary interventions in improving mitochondrial health and reducing inflammation in obesity. By influencing gut microbiota and lowering LPS-mediated signaling, these interventions offer promising strategies for managing metabolic disorders. Future clinical trials may consider monitoring monocyte bioenergetics to evaluate treatment efficacy in metabolic and inflammatory diseases.