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Valencia 2023 MiP2023

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MiPschool 2023

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


Figure. Differences in respiratory capacity and ADP sensitivity in T-cells in response to obesity and different phases of weight loss


Valencia Ana P1,2, Melhorn Susan J3, Schur Ellen A3, Marcinek David J1
  1. Dept of Radiology, Univ of Washington, Seattle, WA, USA
  2. Div of Metabolism, Endocrinology, and Nutrition, Univ of Washington, Seattle, WA, USA
  3. Div of General Internal Medicine, Dept of Medicine, Univ of Washington, Seattle, WA, USA
Corresponding author:

Labels: MiParea: Respiration, mt-Membrane  Pathology: Obesity 

Organism: Human  Tissue;cell: Blood cells 

HRR: Oxygraph-2k  Event: E2