Valencia 2023 MiP2023
T-cell mitochondria exhibit a functional decline with obesity that is aggravated by weight loss. |
Link: MiP2023 Obergurgl AT
Valencia Ana P (2023)
Event: MiP2023 Obergurgl AT
Authors: Valencia Ana P, Melhorn Susan J, Schur Ellen A, Marcinek David J
Introduction: Weight loss (WL) promotes counterregulatory mechanisms that may involve mitochondrial (MITO) function to limit cardiometabolic benefit. This study compared T-cell MITO function in states of obesity (OB), active weight loss (OB-WL), weight loss plateau (OB-PL), regain (OB-RG), and healthy weight (HWC).
Methods: Participants with obesity (61.5%female, 39.5±10.8 yr, BMI 36.7±6.4) underwent a 24-week WL intervention and transmitted their daily weight for 18 months. T-cells (CD3+) were isolated from blood samples obtained at baseline, 6-month, or 12-months. We measured MITO respiratory capacity (MITO-RC) (XFe Analyzer) and sensitivity of membrane depolarization with ADP (IC50) (O2K Fluorespirometer).
Results: Compared to HWC, MITO-RC was lower in OB T-cells (4.1±1.7 vs. 3.3±1.0 pmol O2/106 cells, p<0.05), and even lower in OB-PL (3.0±0.7, p<0.05) and OB-RG (2.7±0.3, p<0.05). Maximal membrane potential was also lower in the OB group and remained low in all phases of WL. IC50 did not differ in T-cells between HWC and OB but was lower in OB-WL and OB-PL (156±15 vs. 7±1 & 22±5, p<0.05).
Conclusions: T-cell MITO respiratory capacity is reduced in obesity and further aggravated in response to WL, particularly following a plateau. However, WL improved ADP sensitivity, suggesting a potential counterregulatory mechanism to meet energy demand. Findings suggest that the MITO function of T-cells is not restored by WL to resemble HWC and is rather altered in a way that could potentially limit cardiometabolic benefit of WL.
• Keywords: ADP sensitivity, peripheral mononuclear cells, weight loss plateau, metabolic adaptation
• O2k-Network Lab: US WA Seattle Valencia A
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Affiliations
- Valencia Ana P1,2, Melhorn Susan J3, Schur Ellen A3, Marcinek David J1
- Dept of Radiology, Univ of Washington, Seattle, WA, USA
- Div of Metabolism, Endocrinology, and Nutrition, Univ of Washington, Seattle, WA, USA
- Div of General Internal Medicine, Dept of Medicine, Univ of Washington, Seattle, WA, USA
- Corresponding author: [email protected]
- Valencia Ana P1,2, Melhorn Susan J3, Schur Ellen A3, Marcinek David J1
Labels: MiParea: Respiration, mt-Membrane
Pathology: Obesity
Organism: Human Tissue;cell: Blood cells
HRR: Oxygraph-2k Event: E2