Maresin 1 Exerts a Tissue-Specific Regulation of Adipo-Hepato-Myokines in Diet-Induced Obese Mice and Modulates Adipokine Expression in Cultured Human Adipocytes in Basal and Inflammatory Conditions.

This study analyses the effects of Maresin 1 (MaR1), a docosahexaenoic acid (DHA)-derived specialized proresolving lipid mediator with anti-inflammatory and insulin-sensitizing actions, on the expression of adipokines, including adiponectin, leptin, dipeptidyl peptidase 4 (DPP-4), cardiotrophin-1 (CT-1), and irisin (FNDC5), both in vitro and in in vivo models of obesity. The in vivo effects of MaR1 (50 μg/kg, 10 days, oral gavage) were evaluated in epididymal adipose tissue (eWAT), liver and muscle of diet-induced obese (DIO) mice. Moreover, two models of human differentiated primary adipocytes were incubated with MaR1 (1 and 10 nM, 24 h) or with a combination of tumor necrosis factor-α (TNF-α, 100 ng/mL) and MaR1 (1-200 nM, 24 h) and the expression and secretion of adipokines were measured in both models.

Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice.

Objective: Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning.

Methods: MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes.

Ptpn1 deletion protects oval cells against lipoapoptosis by favoring lipid droplet formation and dynamics.

Activation of oval cells (OCs) has been related to hepatocyte injury during chronic liver diseases including non-alcoholic fatty liver disease (NAFLD). However, OCs plasticity can be affected under pathological environments. We previously found protection against hepatocyte cell death by inhibiting protein tyrosine phosphatase 1B (PTP1B).

Maresin 1 Regulates Hepatic FGF21 in Diet-Induced Obese Mice and in Cultured Hepatocytes.

Scope: To study the effects of Maresin 1 (MaR1), a docosahexaenoic-acid-derived lipid mediator, on fibroblast growth factor 21 (FGF21) production and to characterize the tissue-specific regulation of Fgf21 and its signaling pathway in liver, skeletal muscle, and white adipose tissue (WAT).

Methods And Results: Diet-induced obese (DIO) mice are treated with MaR1 (50 µg kg , 10 days, oral gavage) and serum FGF21 levels and liver, muscle and WAT Fgf21, β-Klotho, Fgfr1, Egr1, and cFos mRNA expression are evaluated. Additionally, MaR1 effects are tested in mouse primary hepatocytes, HepG2 human hepatocytes, C2C12 myotubes, and 3T3-L1 adipocytes.

Dual role of protein tyrosine phosphatase 1B in the progression and reversion of non-alcoholic steatohepatitis.

Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries. Protein tyrosine phosphatase 1B (PTP1B), a negative modulator of insulin and cytokine signaling, is a therapeutic target for type 2 diabetes and obesity. We investigated the impact of PTP1B deficiency during NAFLD, particularly in non-alcoholic steatohepatitis (NASH).