Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice
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ORIGINAL ARTICLE
Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice L. Martínez-Fernández 1,2 & P. González-Muniesa 1,2,3,4 & N. Sáinz 2 & X. Escoté 2,5 & J. A. Martínez 1,2,3,4 & J. M. Arbones-Mainar 3,6 & M. J. Moreno-Aliaga 1,2,3,4 Received: 28 December 2019 / Accepted: 4 November 2020 # University of Navarra 2020
Abstract Maresin 1 (MaR1) is a DHA-derived pro-resolving lipid mediator. The present study aimed to characterize the ability of MaR1 to prevent the alterations induced by TNF-α on insulin actions in glucose uptake and Akt phosphorylation in cultured human adipocytes from overweight/obese subjects, as well as to investigate the effects of MaR1 acute and chronic administration on Akt phosphorylation in absence/presence of insulin in white adipose tissue (WAT) and skeletal muscle from lean and diet-induced obese (DIO) mice. MaR1 (0.1 nM) prevented the inhibitory effect of TNF-α on insulin-stimulated 2-Deoxy-D-glucose uptake and Akt phosphorylation in human adipocytes. Acute treatment with MaR1 (50 μg/kg, 3 h, i.p.) induced Akt phosphorylation in WAT and skeletal muscle of lean mice. However, MaR1 did not further increase the stimulatory effect of insulin on Akt activation. Interestingly, intragastric chronic treatment with MaR1 (50 μg/kg, 10 days) in DIO mice reduced the hyperglycemia induced by the high fat diet (HFD) and improved systemic insulin sensitivity. In parallel, MaR1 partially restored the impaired insulin response in skeletal muscle of DIO mice and reversed HFD-induced lower Akt phosphorylation in WAT in non-insulin-stimulated DIO mice while did not restore the defective Akt activation in response to acute insulin observed in DIO mice. Our results suggest that MaR1 attenuates the impaired insulin signaling and glucose uptake induced by proinflammatory cytokines. Moreover, the current data support that MaR1 treatment could be useful to reduce the hyperglycemia and the insulin resistance associated to obesity, at least in part by improving Akt signaling. Keywords Maresin 1 . DHA . Insulin sensitivity . n-3 PUFAs derivatives . Glucose uptake Key points • MaR1 attenuates the impaired insulin signaling and glucose uptake induced by TNF-α • Acute and chronic MaR1 treatment promotes Akt signaling in WAT and skeletal muscle * M. J. Moreno-Aliaga [email protected] 1
University of Navarra, Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, Pamplona, Spain
2
University of Navarra, Center for Nutrition Research, School of Pharmacy and Nutrition, Pamplona, Spain
3
CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, Madrid, Spain
4
IDISNA, Navarra’s Health Research Institute, Pamplona, Spain
5
Eurecat, Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, Reus, Spain
6
Adipocyte and Fat Biology Laboratory (AdipoFat), Instituto de Investigación Sanitaria Aragón, Instituto Aragonés de Ciencias de la Salud, Unidad de Investigación Traslacion
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