Year: 2022
Type: article
Abstract: Metabolic syndrome increases risk of complicating co-morbidities. Current clinical indicators reflect established metabolic impairment, preventing earlier intervention strategies. Here we show that circulating sphingolipids are altered in the very early stages of insulin resistance development. The study involved 16 paired overweight but healthy monkeys, one-half of which spontaneously developed metabolic syndrome over the course of 2 years. Importantly, animals did not differ in adiposity and were euglycemic throughout the study period. Using mass spectrometry, circulating sphingolipids, including ceramides and sphingomyelins, were detected and quantified for healthy and impaired animals at both time points. At time of diagnosis, several ceramides were significantly different between healthy and impaired animals. Correlation analysis revealed differences in the interactions among ceramides in impaired animals at diagnosis and pre-diagnosis when animals were clinically indistinguishable from controls. Furthermore, correlations between ceramides and early-stage markers of insulin resistance, diacylglycerols and non-esterified fatty acids, were distinct for healthy and impaired states. Regression analysis identifies coordinated changes in lipid handling across lipid classes as animals progress from healthy to insulin resistant. Correlations between ceramides and the adipose-derived adipokine adiponectin were apparent in healthy animals but not in the metabolically impaired animals, even in advance of loss in insulin sensitivity. These data suggest that circulating ceramides are clinically relevant in identifying disease risk independent of differences in adiposity, and may be important in devising preventative strategies.
Source: Scientific Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,190
Funders: U.S. Department of Veterans Affairs, University of Texas Southwestern Medical Center, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: EXTRAMURAL RESEARCH FACILITIES CONSTRUCTION, Reproductive Hormones in Skeletal Muscle Aging in Rhesus Monkeys, EXTRAMURAL REGIONAL FACILITIES CONSTRUCTION, Metabolism of Alzheimer’s Disease: systems and cellular networks, Adiponectin, A Protein Secreted From Adipose Tissue, G6904138969, Generation of Novel Genetic Tools to Study Cellular Heterogeneity in Adipose Tissues, G7473568262, Caloric Restriction and Aging in Rhesus Monkeys, Wisconsin National Primate Research Center Support, University of Wisconsin Institute for Clinical and Translational Research, White Adipose Tissue Physiology, Mitochondrial Function and Adiponectin, Competing Renewal P01, Molecular Networks in Aging and Caloric Restriction in Rhesus Monkeys, Wisconsin National Primate Research Center Support
OpenAlex ID: W4282965432