Introduction and Objective: Humans with obesity-related insulin resistance (IR) and metabolic dysfunction-associated steatotic liver disease (MASLD) show different mitochondrial alterations. While oxidative phosphorylation (OXPHOS) can be increased in liver, it may be decreased in visceral (VAT), but neither in subcutaneous adipose tissue (SAT) nor skeletal muscle (SM). However, it remains unclear how weight loss affects tissue-specific OXPHOS. We hypothesized that bariatric surgery would induce mitochondrial adaptation mainly in VAT in parallel to improved IR and hepatic lipid content (HLC). Methods: Within the prospective BARIA-DDZ study, participants underwent bariatric surgery (baseline, BL) and elective follow-up (FU) surgery (interval 29±18 months). Whole-body insulin sensitivity (M-value) was measured by hyperinsulinemic-euglycemic clamps, HLC by histology and adipose IR by the Adipo-IR index. During surgery, VAT, SAT, liver and SM biopsies were obtained to assess maximal fatty acid oxidation+complex (C)I+II-linked OXPHOS capacity (CI+IIP) and substrate control ratio (SCR) by high-resolution respirometry and protein expression of CI-CV by Western blotting. Results: At BL, 16 individuals (42±2 years, 75% female, BMI 52±2 kg/m²) featured IR (M-value 3.4±0.5 mg*kg-1*min-1, Adipo-IR 8.1±1.4 mmol*l-1*pmol*l-1) and hepatic steatosis (25.0±6.6%). At FU, they showed 33% weight loss, 62% higher M-value, 59% lower Adipo-IR, and 89% less HLC (all p0.05). CI+IIP increased by 103% in VAT and 38% in SAT, paralleled by a 110% and 54% rise in CV content, respectively (all p0.05); CI-CIV content remained unchanged. In SM and liver CI+IIP and CI-CV content were unchanged. SCR improved only in VAT (13%) and liver (12%; both p0.05). Conclusion: Surgical weight loss improves (i) mitochondrial respiration in VAT and to less extent in SAT, partly via increased mitochondrial biogenesis, and (ii) mitochondrial efficiency in VAT and liver, suggesting a beneficial visceral adipose-liver crosstalk for IR and MASLD. Disclosure K. Pafili: None. K.B. Bódis: Other - travel support; Ended; Sanofi. Other - lecture honoraria; Ended; Pfizer Inc. C. Binsch: None. L. Mastrototaro: None. B. Dewidar: None. G. Heilmann: None. J. Pützer: None. S. Gancheva: None. A. Yavas: None. I. Esposito: None. M. Schlensak: None. F.A. Granderath: None. P. Schrauwen: Consultant; Current; AstraZeneca. Research Support; Ended; Pfizer Inc., MedImmune. S. Kahl: None. M. Roden: Advisory Panel; Current; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Madrigal Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Echosens. Funding The research of KP is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation): Project number 493659010 in the context of the Clinician Scientist Program (FUTURE-4-CSPMM) and by grants from the German Diabetes Research (DZD) foundation and the Heinrich-Heine-University Düsseldorf.
Pafili et al. (Sat,) studied this question.