Deciphering metformin action in obese mice: A critical re-evaluation of established protocols.

Background And Purpose: Despite extensive efforts and a plethora of suggested targets and pathways, the mechanism via which metformin lowers blood glucose remains obscure. Obstacles that hamper progress in understanding metformin action include unexplained discrepancies between preclinical models and patients.

Procedures: We treated obese male C57BL/6J mice fed high fat diet with metformin provided in the form of a single dose, daily intraperitoneal injections, admixture to drinking water, or continuous infusion via intraperitoneal minipumps.

Adipocyte STAT5 deficiency does not affect blood glucose homeostasis in obese mice.

The aim of this study was to investigate whether the lack of signal transducer and activator of transcription 5 (STAT5) in mature adipocytes of obese mice (Stat5Adipoq mice) improves glucose and lipid metabolism as previously observed in lean mice. Male Stat5Adipoq mice and their wild type (WT) littermates were fed high-fat diet (HFD). Effects of adipocyte STAT5 deficiency on adiposity as well as on glucose and lipid metabolism were determined under ad libitum feeding and after weight loss induced by calorie restriction.

Down-regulation of A20 promotes immune escape of lung adenocarcinomas.

Inflammation is a well-known driver of lung tumorigenesis. One strategy by which tumor cells escape tight homeostatic control is by decreasing the expression of the potent anti-inflammatory protein tumor necrosis factor alpha-induced protein 3 (TNFAIP3), also known as A20. We observed that tumor cell intrinsic loss of A20 markedly enhanced lung tumorigenesis and was associated with reduced CD8 T cell-mediated immune surveillance in patients with lung cancer and in mouse models.