Biology subjects

Zhang, Y. L.

Publications and source records attributed to Zhang, Y. L..

2 recordsLinked to original sources

bioRxiv2019

α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation

Beneficial effects of resistance exercise on metabolic health and particularly muscle hypertrophy and fat loss are well established, but the underlying chemical and physiological mechanisms are not fully understood. Here we identified a myometabolite-mediated metabolic pathway that is essential for the beneficial metabolic effects of resistance exercise in vivo. We showed that substantial accumulation of the tricarboxylic acid cycle intermediate -ketoglutaric acid (AKG) is a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is also negatively correlated with BMI. Pharmacological elevation of circulating AKG induces muscle hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysis in vivo. We further found that AKG stimulates the adrenal release of adrenaline through 2-oxoglutarate receptor 1 (OXGR1) expressed in adrenal glands. Finally, by using both loss-of-function and gain-of-function mouse models, we showed that OXGR1 is essential for AKG-mediated exercise-induced beneficial metabolic effects. These findings reveal an unappreciated mechanism for the salutary effects of resistance exercise, using AKG as a systemically-derived molecule for adrenal stimulation of muscle hypertrophy and fat loss.

molecular biology↗

bioRxiv2018

Bioinorganic Angiogenesis

Causing a large diameter blood vessel to sprout branches and a capillary network on demand to create a new angiosome is key to harnessing to potential of regenerative medicine and advancing reconstructive surgery. Currently this can only be achieved by connecting a vein graft to an artery by microsurgery, the arteriovenous loop technique (AVL). The arterial blood pressure in the thin-walled vein is thought to drive remodelling to create branches, however the surgical complexity limits the application of the technique. In this study we demonstrate that unexpectedly, a vessel density of luminal branches in excess of that achieved by the surgical AVL approach can be induced simply by placing a vein in contact with a microporous calcium phosphate. Only osteoinductive biomaterials have been reported previously, this is thought to be the first report of an angio-inductive material. Pilot studies indicated that the material type greatly affected the degree of luminal vascularization. Material contact with the vein is not a requirement for luminal angiogenesis of the vein and together these findings point to a bioinorganic effect, wherein the degradation of the material both releases a stimulatory ionic milieu and creates space for the developing angiosome.

bioengineering↗