Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial
Artikel i vetenskaplig tidskrift, 2024

Background: Mitochondrial dysfunction occurs in monocytes during obesity and contributes to a low-grade inflammatory state; therefore, maintaining good mitochondrial conditions is a key aspect of maintaining health. Dietary interventions are primary strategies for treating obesity, but little is known about their impact on monocyte bioenergetics. Thus, the aim of this study was to evaluate the effects of calorie restriction (CR), intermittent fasting (IF), a ketogenic diet (KD), and an ad libitum habitual diet (AL) on mitochondrial function in monocytes and its modulation by the gut microbiota.
Methods and findings: A randomized controlled clinical trial was conducted in which individuals with obesity were assigned to one of the 4 groups for 1 month. Subsequently, the subjects received rifaximin and continued with the assigned diet for another month. The oxygen consumption rate (OCR) was evaluated in isolated monocytes, as was the gut microbiota composition in feces and anthropometric and biochemical parameters. Forty-four subjects completed the study, and those who underwent CR, IF and KD interventions had an increase in the maximal respiration OCR (p = 0.025, n2p = 0.159 [0.05, 0.27] 95% confidence interval) in monocytes compared to that in the AL group. The improvement in mitochondrial function was associated with a decrease in monocyte dependence on glycolysis after the IF and KD interventions. Together, diet and rifaximin increased the gut microbiota diversity in the IF and KD groups (p = 0.0001), enriched the abundance of Phascolarctobacterium faecium (p = 0.019) in the CR group and Ruminococcus bromii (p = 0.020) in the CR and KD groups, and reduced the abundance of lipopolysaccharide (LPS)-producing bacteria after CR, IF and KD interventions compared to the AL group at the end of the study according to ANCOVA with covariate adjustment. Spearman's correlation between the variables measured highlighted LPS as a potential modulator of the observed effects. In line with this findings, serum LPS and intracellular signaling in monocytes decreased with the three interventions (CR, p = 0.002; IF, p = 0.001; and KD, p = 0.001) compared to those in the AL group at the end of the study. Conclusions: We conclude that these dietary interventions positively regulate mitochondrial bioenergetic health and improve the metabolic profile of monocytes in individuals with obesity via modulation of the gut microbiota. Moreover, the evaluation of mitochondrial function in monocytes could be used as an indicator of metabolic and inflammatory status, with potential applications in future clinical trials.
Trial registration: This trial was registered with ClinicalTrials.gov (NCT05200468).

Gut microbiota

Dietary interventions

Monocyte bioenergetics

Obesity

Mitochondrial function

Författare

Martha Guevara-Cruz

Instituto Nacional de la Nutricion Salvador Zubiran

Karla G. Hernández-Gómez

Instituto Nacional de la Nutricion Salvador Zubiran

Citlally Condado-Huerta

Instituto Nacional de la Nutricion Salvador Zubiran

Luis E. González-Salazar

Instituto Nacional de la Nutricion Salvador Zubiran

Ana Karen Peña-Flores

Instituto Nacional de la Nutricion Salvador Zubiran

Edgar Pichardo-Ontiveros

Instituto Nacional de la Nutricion Salvador Zubiran

Aurora E. Serralde-Zúñiga

Instituto Nacional de la Nutricion Salvador Zubiran

Mónica Sánchez-Tapia

Instituto Nacional de la Nutricion Salvador Zubiran

Otoniel Maya Lucas

Chalmers, Fysik, E-commons

Isabel Medina-Vera

Instituto Nacional de Pediatría

Lilia G. Noriega

Instituto Nacional de la Nutricion Salvador Zubiran

Adriana López-Barradas

Instituto Nacional de la Nutricion Salvador Zubiran

Oscar Rodríguez-Lima

Universidad Nacional Autónoma de México, Facultad de Medicina

Irma Mata

Instituto Nacional de la Nutricion Salvador Zubiran

Viridiana Olin–Sandoval

Centro de Investigacion y de Estudios Avanzados (CINVESTAV)

Nimbe Torres

Instituto Nacional de la Nutricion Salvador Zubiran

Armando R. Tovar

Instituto Nacional de la Nutricion Salvador Zubiran

Laura A. Velázquez-Villegas

Instituto Nacional de la Nutricion Salvador Zubiran

Clinical Nutrition

0261-5614 (ISSN) 15321983 (eISSN)

Vol. 43 8 1914-1928

Ämneskategorier

Pediatrik

Neurovetenskaper

Näringslära

DOI

10.1016/j.clnu.2024.06.036

Mer information

Senast uppdaterat

2024-08-02