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In this study, we aimed to determine whether liraglutide could effectively reduce insulin resistance (IR) by regulating Sestrin2 (SESN2) expression in L6 rat skeletal muscle cells by examining its interactions with SESN2, autophagy, and IR. L6 cells were incubated with liraglutide (10–1000 nM) in the presence of palmitate (PA; 0.6 mM), and cell viability was detected using the cell counting kit-8 (CCK-8) assay. IR-related and autophagy-related proteins were detected using western blotting, and IR and autophagy-related genes were analyzed using quantitative real-time polymerase chain reaction. Silencing SESN2 was used to inhibit the activities of SESN2. A reduction in insulin-stimulated glucose uptake was observed in PA-treated L6 cells, confirming IR. Meanwhile, PA decreased the levels of GLUT4 and phosphorylation of Akt and affected SESN2 expression. Further investigation revealed that autophagic activity decreased following PA treatment, but that liraglutide reversed this PA-induced reduction in autophagic activity. Additionally, silencing SESN2 inhibited the ability of liraglutide to up-regulate the expression of IR-related proteins and activate autophagy signals. In summary, the data showed that liraglutide improved PA-induced IR in L6 myotubes by increasing autophagy mediated by SESN2. [ABSTRACT FROM AUTHOR]

• Novel adipocytokines may form part of an important pathogenic mechanism of CAD. • Inflammatory cell infiltration could serve as promising medicating targets of CAD. • Increased number of blood vessels could lead to the onset and development of CAD. • EAT inflammation may be part of the pathological mechanism of CAD. This study investigates the expression of novel adipocytokines and inflammatory cells infiltration in epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) between 27 coronary artery disease (CAD) and 21 non-CAD (NCAD) patients enrolled from September 2020 to September 2021. Serum, gene, and protein expression levels of the novel adipocytokines were determined using ELISA, RT-qPCR, and western blot analyses. The number of blood vessels and adipocytes morphology were measured via hematoxylin-eosin staining, and inflammatory cells infiltration was examined via immunohistochemistry. Serum ANGPTL8, CTRP5, and Wnt5a levels were higher in the CAD than in the NCAD group, while serum CTRP3, Sfrp5, and ZAG levels were lower in the CAD than in the NCAD group. Compared to the EAT of NCAD and SAT of CAD patients, the EAT of CAD patients had higher mRNA levels of ANGPTL8, CTRP5, and Wnt5a while lower levels of CTRP3, Sfrp5, and ZAG; higher protein expression levels of ANGPTL8 and CTRP5 but lower levels of CTRP3; more blood vessels; and higher infiltration rates of macrophages (CD68 +), pro-inflammatory M1 macrophages (CD11c +), mast cells (Tryptase +), T lymphocytes (CD3 +), and B lymphocytes (CD20 +) but lower infiltration rates of anti-inflammatory M2 macrophages (CD206 +). Novel adipocytokines and inflammatory cells infiltration are dysregulated in human EAT, and could be important pathophysiological mechanisms and novelly promising medicating targets of CAD. [ABSTRACT FROM AUTHOR]