Myonectin (CTRP15), a Novel Myokine That Links Skeletal Muscle to Systemic Lipid Homeostasis

Abstract

Background: Skeletal muscle-derived myokines modulate metabolic, inflammatory, and other processes. Results: Myonectin, a novel myokine whose expression and circulating levels are regulated by diet, metabolic state, and exercise, functions to control lipid metabolism. Conclusion: Myonectin is a potential nutrient-responsive metabolic regulator secreted by muscle. Significance: Myonectin links muscle to systemic lipid metabolism via its action on adipocytes and hepatocytes, providing insight into complex tissue cross-talk.

Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia

“…Similarly, ERFE was not detectable in 3-, 6-, and 12-week-old WT mice, but Th3/1 mice exhibited massively increased circulating concentration of ERFE (25 ng/mL at 3 weeks of age and 10 ng/mL at 6 and 12 weeks of age) ( Figure 4B). Because ERFE has been previously described as a regulator whole-body fatty acid metabolism, 26 we assayed ERFE levels in the plasma of WT and Apoe-deficient mice fed 2 months with either a lowfat diet or a Western diet 23 (male mice, n 5 5 for each of the 4 groups). Interestingly, ERFE was not detectable in any of these groups, suggesting that the production of ERFE during the regulation of energy metabolism may not be stimulated or is negligible compared with its production by erythroid cells during increased erythropoietic activity.…”

Adipose tissue-derived cytokines, CTRPs as biomarkers and therapeutic targets in metabolism and the cardiovascular system

“…Novel metabolic/immune regulator; modulating both inflammation and insulin sensitivity; regulates fat development; alleviates AngII-induced hypertension and vascular endothelial dysfunction; potential therapeutic target for the prevention of skin fibrosis; endogenous complement regulator [5,29,68,69] 7 Adipose tissue, lung Improves insulin sensitivity; beneficial metabolic outcomes in the setting of obesity and diabetes [9,54] 8 (8B) Lung, testis, absent in mice Blocks glioblastoma dissemination within the brain [14,70] 9 (9A,9B) Cardiac tissue, adipose tissue Important in the development of type 2 diabetes; novel metabolic regulator and a new component of the metabolic network that links adipose tissue to lipid metabolism in skeletal muscle and liver; prevents vascular restenosis after angioplasty, hepatic steatosis and hypertension; stabilizes plaque, improves endothelial cell survival and function [12,20,48,[71][72][73] 10 Eye, adipose tissue Regulates metabolism, adipose tissue homeostasis [3,23] 11 Adipose tissue New regulator of adipogenesis; maintains adipose tissue homeostasis [3,74] 12 Adipose tissue Novel biomarkers for the prediction and early diagnosis of T2DM; regulates glucose and lipid metabolism and whole-body glucose homeostasis [24,50,51,75,76] 13 Adipose tissue, brain Associated with increased risk of T2DM and coronary artery disease and non-alcoholic fatty liver disease; negative association with metabolism; modulates whole-body energy balance [2,24,27,77,78] 14 Brain, adipose tissue Promotes tissue regeneration, and recovery of ischemic heart disease; maintains adipose tissue homeostasis by generating complexes with CTRP11 [74] 15 Skeletal muscle Modulates energy homeostasis and metabolic circuit; modulates inter-tissue crosstalk [21,79] ISR: in-stent restenosis; PCI: percutaneous coronary intervention; DES: d...…”

“…CTRP9 and CTRP15 are considered as cardiokine (the heart-derived proteins are termed cardiokines) due to their high profile in the cardiac tissue and for their protective and preventive actions against cardiovascular injury. Although the CTRP9's functional receptor has not been thoroughly investigated, cadherin family appears to be a potential candidate [21] . Loss of CTRP12 af fects the glucose and lipid metabolism in the obese and insulin-resistant mouse models [22] .…”

“…CTRP13 regulates the metabolism through AMPK activation and decrease of fatty acid-induced JNK signaling [23] . CTRP15 links skeletal muscle and liver to systemic lipid homeostasis [21] . We summarize current understanding of CTRPs metabolic functions and provide insight into the dynamic regulatory role of CTRP on metabolic balance.…”

“…CTRP1 and CTRP12 show opposite changes in the concentration, while CTRP3 may have a beneficial effect on the prevention of vascular remodeling through anti-inflammator y actions providing a promising strategy for the therapy of vascular disease linked to obesity [42,24] . CTRP6, although it has no effect on collagen or fibroblasts proliferation, does suppress in response to alterations in energy state and predicting changes in the metabolic circuit [21] . Therefore, among the CTRPs, CTRP1 displays the potential to serve as a marker and therapeutic target in the vascular system and CTRP3 exhibits biomarker features in patients with diabetic-related PDR [45] .…”