Bariatric surgery rapidly improves mitochondrial respiration in morbidly obese patients

Abstract

Obesity and its attendant comorbidities are an emerging epidemic. Chronic metabolic inflammation (metainflammation) is thought to precipitate obesity-associated morbidities; however, its mechanistic progression is poorly understood. Moreover, although interventions such as diet, exercise, and bariatric surgery can control body weight, their effects on metainflammation are also poorly understood. Recently, metainflammation and the pathobiology of obesity have been linked to mitochondrial dysfunction. Herein we examined the effects of bariatric surgery on mitochondrial respiration as an index of resolving metainflammation in morbidly obese patients. This institutional review board-approved study involved morbidly obese patients (body mass index > 35 kg/m(2)) undergoing sleeve gastrectomy or Roux-en-Y gastric bypass. Mitochondrial respiration was assessed in peripheral blood monocytes and in skeletal muscle samples before surgery and at 12 weeks after surgery. Patient biometrics, homeostasis model assessment-estimated insulin resistance (HOMA-IR) score, C-reactive protein, and lipid profile were analyzed. Twenty patients were enrolled and showed an average percent excess body weight loss of 30.3% weight loss at 12 weeks after surgery. Average HOMA-IR score decreased from 3.0 to 1.2 in insulin-resistant patients. C-reactive protein, an index of metainflammation, showed a modest decrease. Lipid profile remained stable. Intriguingly, mitochondrial basal and maximal respiration rates in peripheral blood monocytes increased after surgery. Basal rates of skeletal muscle mitochondrial respiration were unchanged, but the maximal respiration rate trended toward an increase after surgery. Cellular and tissue mitochondrial respiration increased in a morbidly obese patient cohort after laparoscopic bariatric surgery. These changes were consistent in patients with postsurgical weight loss. Importantly, no significant changes or improvements occurred in canonical indices used to assess recovery after bariatric surgery over this short time course. Thus, increased mitochondrial respiration may represent a novel biomarker of early improvement and positive outcome after surgery in morbidly obese patients.