Calorie restriction modulates mitochondrial dynamics and autophagy in leukocytes of patients with obesity

• Published in: Free radical biology & medicine Vol. 225; pp. 677 - 686
• Main Authors: Abad-Jiménez, Zaida, López-Domènech, Sandra, Pelechá, María, Perea-Galera, Laura, Rovira-Llopis, Susana, Bañuls, Celia, Blas-García, Ana, Apostolova, Nadezda, Morillas, Carlos, Víctor, Víctor Manuel, Rocha, Milagros
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.11.2024
• Subjects: Adult; Autophagy; Beclin-1 - genetics; Beclin-1 - metabolism; Caloric Restriction - methods; Dynamins - genetics; Dynamins - metabolism; Female; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; Humans; Leukocytes - metabolism; Leukocytes - pathology; Male; Membrane Potential, Mitochondrial; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Middle Aged; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial Dynamics; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Mitochondrial quality control; Obesity; Obesity - diet therapy; Obesity - metabolism; Obesity - pathology; Oxidative stress; PBMCs; Reactive Oxygen Species - metabolism; VLCD; Obesity; Oxidative stress; PBMCs; Autophagy; Mitochondrial quality control; VLCD
• ISSN: 0891-5849; 1873-4596; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2024.10.295

Although it is established that caloric restriction offers metabolic and clinical benefits, the molecular mechanisms underlying these effects remain unclear. Thus, this study aimed to investigate whether caloric restriction can modulate mitochondrial function and remodeling and stimulate autophagic flux in the PBMCs of patients with obesity. This was an interventional study of 38 obese subjects (BMI >35 kg/m2) who underwent 6 months of dietary therapy, including a 6-week very-low-calorie diet (VLCD) followed by an 18-week low-calorie diet (LCD). We determined clinical variables, mitochondrial function parameters (by fluorescence imaging of mitochondrial ROS and membrane potential), and protein expression of markers of mitochondrial dynamics (MNF1, MFN2, OPA, DRP1 and FIS1) and autophagy (LC3, Beclin, BCL2 and NBR1) by Western blot. Caloric restriction induced an improvement in metabolic outcomes that was accompanied by an increase in AMPK expression, a decrease of mitochondrial ROS and mitochondrial membrane potential, which was associated with increased markers of mitochondrial dynamics (MFN2, DRP1 and FIS1) and activation of autophagy as evidenced by augmented LC3 II/I, Beclin1 and NBR1, and a decrease in BCL2. These findings shed light on the specific molecular mechanisms by which caloric restriction facilitates metabolic improvements, highlighting the relevance of pathways involving energy homeostasis and cell recovery, including mitochondrial function and dynamics and autophagy. [Display omitted] •38 patients with obesity underwent a 6-month hipocaloric diet.•Caloric restriction improved metabolism by modulating mitochondria and reducing ROS.•Enhanced mitochondrial dynamics and autophagy are key in caloric restriction benefits.•AMPK expression aids mitochondrial remodeling and energy homeostasis in restriction.•Insights could lead to new obesity therapies, including pharmacological targets.