Effect of mitratapide on body composition, body measurements and glucose tolerance in obese Beagles

The objective of this study was to confirm that weight loss after treatment with mitratapide (Yarvitan®) is loss of adipose tissue. Obese dogs were treated with the recommended treatment schedule of mitratapide. Dual-energy X-ray absorptiometry (DEXA) was done before and after the treatment schedule. Body weight, feed consumption and pelvic circumference were recorded and a glucose tolerance test was performed. Dual-energy X-ray absorptiometry measurements showed an impressive loss of fat tissue, corresponding to a mean loss of approximately 41.6% of the body fat mass recorded before treatment. After treatment with mitratapide, the mean body fat percentage had returned within the normal range. At the end of the study, the dogs had lost on average 14.2% of their body weight and 15.2% of their pelvic circumference compared to baseline. The results also suggest that losing weight with mitratapide might help to reverse insulin resistance

Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism.

HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic ATP production through activation of a Pparalpha pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress