Improved Muscle Mitochondrial Capacity Following Gastric Bypass Surgery in Obese Subjects

Abstract

Background: Weight loss resulting from low-calorie diets is often less than expected. We hypothesized that energy restriction would influence proton leakage and improve mitochondrial efficiency, leading to reduced energy expenditure, partly explaining the difficulties in weight loss maintenance. Methods: Eleven women with a median BMI of 38.5 kg/m2 (q-range 37–40), and referred to gastric bypass surgery participated. Before surgery, and at 6 months of follow-up, muscle biopsies were collected from the vastus lateralis muscle. Mitochondria were isolated and analyzed for coupled (state 3) and uncoupled (state 4) respiration and mitochondrial capacity (P/O ratio). Results: At follow-up, the participants had a median BMI of 29.6 kg/m2 (28.3–32.0). State 3 increased from 20.6 (17.9–28.9) to 34.9 nmol O2/min/U citrate synthase (CS) (27.0–49.0), p = 0.01, while state 4 increased from 2.8 (1.8–4.2) to 4.2 nmol O2/min/U CS (3.1–6.1), although not statistically significant. The P/O ratio increased from 2.7 (2.5–2.8) to 3.2 (3.0–3.4), p = 0.02, indicating improved mitochondrial efficiency. Conclusions: Six months after gastric bypass surgery, the mitochondrial capacity for coupled, i.e., ATP-generating, respiration increased, and the P/O ratio improved. Uncoupled respiration was not enhanced to the same extent. This could partly explain the decreased basal metabolism and the reduced inclination for weight loss during energy restriction.