Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism

Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain- containing 5 （FNDC5） protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue （WAT） and uncoupling protein I （UCP1） expression, leading to an increase in total body energy expenditure by augmented UCPl-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone-tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal （IP） administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-kB ligand （RANKL）- induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice.

Unraveling complexity of interconnected regulatory circuits in lipid metabolism

In this issue of Journal of Biomedical Research,3review articles are published that cover a broad range of topics addressing current understanding on regulation of nutrient metabolism through protein phosphatases,homeostatic regulation of cellular lipid droplets by small GTPases,and mechanisms by which hepatic assembly and secretion of triglyceride-rich lipoproteins are regulated.

Research Progress on Prevention and Treatment of Glucolipid Metabolic Disease with Integrated Traditional Chinese and Western Medicine

Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settings. However, increasing of the disease incidence, lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattem of the single disease, single target therapy, that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine （WM）. On the basis of the combination of the advantages of integrated Chinese medicine （CM） and WM, with unified understanding of such diseases, the new concept of glucolipid metabolic disease （GLMD） is introduced. In this new concept, disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD. The key points of pathology included dysfunction of neuronal-endocrine-immune system,insulin resistance, oxidative stress, inflammation and intestinal flora imbalance. In the core pathogenic perspective of CM, it can be explained as ＂Gan （Liver） Shi Shu Xie＂ （dysfunction of Gan in metabolism and emotion regulation） that will lead to the occurence/production of endogenous dampness and phlegm, blood stasis and turbid. This leads to the new concept of ＂Liver-based regulatory system for metabolic homeostasis＂ to be introduced further. The comprehensive prevention and control strategy ＂Tiao Gan Qi Shu Hua Zhuo＂ （modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness）. Its representative formula Fufang Zhenzhu Tiaozhi Capsule （复方贞术调脂胶囊） is innovated under such rationales. Comment for some commonly-used CM GLMD therapeutic drugs was presented. High-level evidence-based and epidemiological and mechanism studies should be carded out to further interpret and explain of the scientific connotation of GLMD.