Metabolic recovery after weight loss surgery is reflected in serum microRNAs

[Abstract] INTRODUCTION: Bariatric surgery offers the most effective treatment for obesity, ameliorating or even reverting associated metabolic disorders, such as type 2 diabetes. We sought to determine the effects of bariatric surgery on circulating microRNAs (miRNAs) that have been implicated in the metabolic cross talk between the liver and adipose tissue. RESEARCH DESIGN AND METHODS: We measured 30 miRNAs in 155 morbidly obese patients and 47 controls and defined associations between miRNAs and metabolic parameters. Patients were followed up for 12 months after bariatric surgery. Key findings were replicated in a separate cohort of bariatric surgery patients with up to 18 months of follow-up. RESULTS: Higher circulating levels of liver-related miRNAs, such as miR-122, miR-885-5 p or miR-192 were observed in morbidly obese patients. The levels of these miRNAs were positively correlated with body mass index, percentage fat mass, blood glucose levels and liver transaminases. Elevated levels of circulating liver-derived miRNAs were reversed to levels of non-obese controls within 3 months after bariatric surgery. In contrast, putative adipose tissue-derived miRNAs remained unchanged (miR-99b) or increased (miR-221, miR-222) after bariatric surgery, suggesting a minor contribution of white adipose tissue to circulating miRNA levels. Circulating levels of liver-derived miRNAs normalized along with the endocrine and metabolic recovery of bariatric surgery, independent of the fat percentage reduction. CONCLUSIONS: Since liver miRNAs play a crucial role in the regulation of hepatic biochemical processes, future studies are warranted to assess whether they may serve as determinants or mediators of metabolic risk in morbidly obese patients.

SS-A was recipient of a travel/visiting scientist fellowship “José Castillejo” from the Ministerio de Educación, Cultura y Deporte-Spain. Project Nº PI16/00884 was awarded to FC and SS-A integrated in the Spanish National Plan for Scientific Research, Development and Technological Innovation 2013–2016 and funded by the ISCIII. CG is funded by a British Heart Foundation (BHF) PhD studentship (FS/18/60/34181). MM is a BHF Chair Holder (CH/16/3/32406) with BHF program grant support (RG/16/14/32397). MM was awarded a BHF Special Project grant to participate in the ERA-CVD Transnational Grant “MacroERA: Noncoding RNAs in cardiac macrophages and their role in heart failure” and is part of the Marie Skłodowska-Curie Innovative Training Network TRAIN-HEART (http://train-heart.euhttp://train-heart.eu) as well as a networks on “MicroRNAbased Therapeutic Strategies in Vascular Disease” and on “Defining the Roles of Smooth Muscle Cells and other Extracellular Matrix Producing Cells in Late Stage Atherosclerotic Plaque Formation” funded by the Fondation Leducq. This work was supported by the National Institute of Health Research Biomedical Research Centre based at Guy’s and St Thomas’ NHS (National Health Service) Foundation Trust and King’s College London in partnership with King’s College Hospital and an R&D K-Centre and the excellence initiative VASCage (Centre for Promoting Vascular Health in the Ageing Community, project number 868624) of the Austrian Research Promotion Agency FFG (COMET program—Competence Centers for Excellent Technologies) funded by the Austrian Ministry for Transport, Innovation and Technology, the Austrian Ministry for Digital and Economic Affairs and the federal states Tyrol (via Standortagentur), Salzburg and Vienna (via Vienna Business Agency).

info:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/PI16%2F00884/ES/RELACION ENTRE MARCADORES HORMONALES DE CONTROL DE LA INGESTA Y GASTO METABÓLICO. EFECTO DEL BALANCE ENERGÉTICO NEGATIVO Y LA MODIFICACIÓN DE GH

Bristish Heart Foundation; FS/18/60/34181

Bristish Heart Foundation; RG/16/14/32397