MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways

The MAP kinase-interacting kinases (MNK1 and MNK2) are non-essential enzymes which are activated by MAP kinases. They are implicated in controlling protein synthesis. Here we show that mice in which the expression of either MNK1 or MNK2 has been knocked out (KO) are protected against adverse effects of high-fat feeding, and in distinct ways. High-fat diet (HFD)-fed MNK2-KO show less weight gain than wild-type animals, and improved glucose tolerance, better insulin sensitivity and markedly diminished adipose tissue inflammation. This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology. MNK1-KO/HFD mice show better glucose tolerance and insulin sensitivity, but gain weight and show similar adipose inflammation to WT animals. These data suggest MNK1 participates in mediating HFD-induced insulin resistance. Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease

Pharmacotherapies for COPD

This review article summarizes the main treatments for chronic obstructive pulmonary disease, their mechanisms, and the key evidence from trials supporting their use. Drug classes covered were short acting beta agonists (SABA), short acting muscarinic antagonists (SAMA), long acting beta agonists (LABA), long acting antimuscarinics (LAMA), inhaled corticosteroids (ICS), LABA/ICS combinations, specific phosphodiesterase (PDE4) inhibitors, non-specific PDE inhibitors, mucolytics, and oxygen. Non-specific therapies, such as opiates for relief of dyspnoea and therapies for smoking cessation, are also covered briefly. For each class of drug, mechanisms of action are described, key clinical trial results are reported, and available agents compared. Finally, the place of each drug in therapy is compared between current worldwide guidelines