Oxylipin responses to fasting and insulin infusion in a large mammalian model of fasting-induced insulin resistance, the northern elephant seal
Year: 2021
Type: article
Abstract: The prolonged, postweaning fast of northern elephant seal ( Mirounga angustirostris) pups is characterized by a reliance on lipid metabolism and reversible, fasting-induced insulin resistance, providing a unique model to examine the effects of insulin on lipid metabolism. We have previously shown that acute insulin infusion induced a shift in fatty acid metabolism dependent on fasting duration. This study complements the previous study by examining the effects of fasting duration and insulin infusion on circulating levels of oxylipins, bioactive metabolites derived from the oxygenation of polyunsaturated fatty acids. Northern elephant seal pups were studied at two postweaning periods ( n = 5/period): early fasting (1–2 wk postweaning; 127 ± 1 kg) and late fasting (6–7 wk postweaning; 93 ± 4 kg). Different cohorts of pups were weighed, sedated, and infused with 65 mU/kg of insulin. Plasma was collected prior to infusion (T0) and at 10, 30, 60, and 120 min postinfusion. A profile of ∼80 oxylipins was analyzed by UPLC-ESI-MS/MS. Nine oxylipins changed between early and late fasting and eight were altered in response to insulin infusion. Fasting decreased prostaglandin F2α (PGF2α) and increased 14,15-dihydroxyicosatrienoic acid (14,15-DiHETrE), 20-hydroxyeicosatetraenoic acid (20-HETE), and 4-hydroxy-docosahexaenoic acid (4-HDoHE) ( P < 0.03) in T0 samples, whereas insulin infusion resulted in an inverse change in area-under-the-curve (AUC) levels in these same metabolites ( P < 0.05). In addition, 12-12-hydroperoxyeicosatetraenoic acid (HpETE) and 12-HETE decreased with fasting and insulin infusion, respectively ( P < 0.04). The oxylipins altered during fasting and in response to insulin infusion may contribute to the manifestation of insulin resistance and participate in the metabolic regulation of associated cellular processes.
Authors: Dana N. Wright, Kondwani G. H. Katundu, Jose A. Viscarra, Daniel E. Crocker, John W. Newman, Michael R. La Frano, Rudy M. Ortiz
Institutions: California Polytechnic State University, University of Malawi, University of California, Merced, Sonoma State University, National Institutes of Health, Agricultural Research Service, United States Department of Agriculture, Western Human Nutrition Research Center, University of California, Davis
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Agriculture, California Polytechnic State University, San Luis Obispo, National Institutes of Health, University of California, Davis, National Heart, Lung, and Blood Institute, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1311054762, G1444661466, G1485084580, G1488703235, G2293003199, West Coast Central Comprehensive Metabolomics Resource Core (WC3MRC), G3014993624, Nutritional antecedents of chronic diseases and disorders in low-income populatio, G3738150164, G6739180201, G6806856224, G76794246, Independent Scientist Development Award in Oxidative Stress and Apnea, G9000033486
OpenAlex ID: W3193229455