Absence of leptin has been associated with reduced skeletal muscle mass in leptin-deficient ob/ob mice. The aim of our study was to examine the effect of leptin on the catabolic and anabolic pathways regulating muscle mass. Gastrocnemius, extensor digitorum longus and soleus muscle mass as well as fiber size were significantly lower in ob/ob mice compared to wild type littermates, being significantly increased by leptin administration (P<0.001). This effect was associated with an inactivation of the muscle atrophy-related transcription factor forkhead box class O3 (FoxO3a) (P<0.05), and with a decrease in the protein expression levels of the E3 ubiquitin-ligases muscle atrophy F-box (MAFbx) (P<0.05) and muscle RING finger 1 (MuRF1) (P<0.05). Moreover, leptin increased (P<0.01) protein expression levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a regulator of muscle fiber type, and decreased (P<0.05) myostatin protein, a negative regulator of muscle growth. Leptin administration also activated (P<0.01) the regulators of cell cycle progression proliferating cell nuclear antigen (PCNA) and cyclin D1, and increased (P<0.01) myofibrillar protein troponin T. The present study provides evidence that leptin treatment may increase muscle mass of ob/ob mice by inhibiting myofibrillar protein degradation as well as enhancing muscle cell proliferation.

The beneficial actions of n‐3 fatty acids on obesity‐induced insulin resistance and inflammation have been related to the synthesis of specialized proresolving lipid mediators (SPMs) like resolvins. The aim of this study was to evaluate the ability of one of these SPMs, maresin 1 (MaR1), to reverse adipose tissue inflammation and/or insulin resistance in two models of obesity: diet‐induced obese (DIO) mice and genetic (ob/ob) obese mice. In DIO mice, MaR1 (2 mg/kg; 10 d) reduced F4/80‐positive cells and expression of the proinflammatory M1 macrophage phenotype marker Cd11c in white adipose tissue (WAT). Moreover, MaR1 decreased Mcp‐1, Tnf‐a, and Il‐1b expression, upregulated adiponectin and Glut‐4, and increased Akt phosphorylation in WAT. MaR1 administration (2 mg/kg; 20 d) to ob/ob mice did not modify macrophage recruitment but increased the M2 macrophage markers Cd163 and Il‐10. MaR1 reduced Mcp‐1, Tnf‐a, Il‐1b, and Dpp‐4 and increased adiponectin gene expression in WAT. MaR1 treatment also improved the insulin tolerance test of ob/ob mice and increased Akt and AMPK phosphorylation in WAT. These data suggest that treatment with MaR1 can counteract the dysfunctional inflamed WAT and could be useful to improve insulin sensitivity in murine models of obesity.—Martínez‐Fernández, L., González‐Muniesa, P., Laiglesia, L. M., Sáinz, N., Prieto‐Hontoria, P. L., Escoté, X., Odriozola, L., Corrales, F. J., Arbones‐Mainar, J. M., Martínez, J. A., Moreno‐Aliaga, M. J. Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in ob/ob and diet‐induced obese mice. FASEB J. 31, 2135–2145 (2017). www.fasebj.org