Journal Article

Metabolomic profiling identifies complex lipid species and amino acid analogues associated with response to weight loss interventions

Bihlmeyer, Nathan A., Shah, Svati H., Pagidipati, Neha J., Kraus, William E., Clish, Clary B., Gerszten, Robert E., Deik, Amy Anderson, Newgard, Christopher B., Laferrère, Blandine, Kwee, Lydia Coulter, Svetkey, Laura P.

2021

Overview

Obesity is an epidemic internationally. While weight loss interventions are efficacious, they are compounded by heterogeneity with regards to clinically relevant metabolic responses. Thus, we sought to identify metabolic biomarkers that are associated with beneficial metabolic changes to weight loss and which distinguish individuals with obesity who would most benefit from a given type of intervention. Liquid chromatography mass spectrometry-based profiling was used to measure 765 metabolites in baseline plasma from three different weight loss studies: WLM (behavioral intervention, N = 443), STRRIDE-PD (exercise intervention, N = 163), and CBD (surgical cohort, N = 125). The primary outcome was percent change in insulin resistance (as measured by the Homeostatic Model Assessment of Insulin Resistance [%ΔHOMA-IR]) over the intervention. Overall, 92 individual metabolites were associated with %ΔHOMA-IR after adjustment for multiple comparisons. Concordantly, the most significant metabolites were triacylglycerols (TAGs; p = 2.3e-5) and diacylglycerols (DAGs; p = 1.6e-4), with higher baseline TAG and DAG levels associated with a greater improvement in insulin resistance with weight loss. In tests of heterogeneity, 50 metabolites changed differently between weight loss interventions; we found amino acids, peptides, and their analogues to be most significant (4.7e-3) in this category. Our results highlight novel metabolic pathways associated with heterogeneity in response to weight loss interventions, and related biomarkers which could be used in future studies of personalized approaches to weight loss interventions.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Amino acids / Bile acids / Biology and Life Sciences / Biomarkers / Biomarkers - blood / Body Mass Index / Body weight loss / Cardiovascular diseases / Chromatography / Computer and Information Sciences / Consent / Developing countries / Diabetes / Diabetes mellitus / Diabetes mellitus (non-insulin dependent) / Diet / Dietary intake / Diglycerides - blood / Dyslipidemia / Epidemics / Exercise / Fatty acids / Female / Gastrointestinal surgery / Health care facilities / Heart diseases / Humans / Hypertension / Identification and classification / Insulin resistance / Insulin Resistance - physiology / Intervention / LDCs / Lipid Metabolism - physiology / Lipids / Lipids - blood / Male / Mass Spectrometry / Medicine / Medicine and Health Sciences / Metabolites / Metabolomics / Methodology / Methods / Middle Aged / Negative ions / Obesity / Obesity - blood / Obesity - metabolism / Obesity - surgery / Obesity - therapy / Overweight / Phlebotomy / Physical activity / Physical fitness / Physical Sciences / Physiological aspects / Physiology / Plasma / Polarity / Research and Analysis Methods / Triglycerides - blood / Weight control / Weight loss / Weight Loss - physiology