Stress-induced myonectin improves glucose homeostasis by inhibiting glycemic response to HPA axis

Abstract

One Sentence Summary: Chronic stress breaks glucose intolerance cycle to resist diet-induced obesity, through myonectin-mediated inhibition of glycemic response to epinephrine (EPI) and activation of insulin signaling in adipose tissues. GraphicalAbstract Stress AAV+ Sympathetic output HFD 2wk Glucose intolerance 4wk Insulin sensitivity ↓ EPI sensitivity ↑ 3wk Glucose intolerance↑ Insulin sensitivity↑ Insulin sensitivity↑↑ P-Akt Ser473↑ EPI sensitivity↑ Thermogenesis↑ Insulin sensitivity↑ P-Akt Ser473↑ EPI sensitivity↑ Lipolysis↑ Myonectin↑ BAT WAT Improved Glycemic Control Stress diet Improved Metabolic Profile Glucose Intolerance Cycle ? ? Obesity Highlights  EPI sensitivity increases after glucose intolerance and with reduced insulin sensitivity in diet-induced obesity  Chronic stress blunts glycemic responses to EPI and increases myonectin levels in serum and skeletal muscle  Myonectin attenuates glycemic response to EPI and improves metabolic profile in HFD-fed mice  Reducing myonectin reverses beneficial effects of stress on glucose homeostasis AbstractInhibiting glycemic response to HPA axis contributes to glycemic control for diabetic patients.Here, mice were subjected to high-fat diet and intermittent chronic stress, and glucose homeostasis and lipolysis were determined during the intervention. Firstly, we found that glucose intolerance appears at the earliest, followed by reduced insulin sensitivity and increased epinephrine (EPI) sensitivity in the early stage of diet-induced obesity. Next we investigated whether chronic stress impairs glycemic control and which mediates its effects. Short-term stress training raises serum and skeletal muscle myonectin (Myn) levels and improves glucose intolerance. Stress attenuates blood glucose and glycerol responses to EPI, but enhances lipolytic response to EPI in adipose tissues. Myn overexpression in vivo improves glucose tolerance and enhances insulin sensitivity at the cost of blunting glycemic responses to EPI. Myn knockdown reduces beneficial effects of stress or exercise on glucose homeostasis. Together, myonectin is a stress-induced myokine that readjusts glycemic and metabolic responses to HPA axis, and thus prevent the progression of glucose intolerance and obesity. Clin Endocrinol Metab 92(7): JS, Samuel VT (2014) Targeting steroid receptor coactivator 1 with antisense oligonucleotides increases insulin-stimulated skeletal muscle glucose uptake in chow-fed and high-fat-fed male rats. Am J Physiol Endocrinol Metab 307(9): E773-E783 Chuang JC, Krishnan V, Yu HG, Mason B, Cui H, Wilkinson MB, Zigman JM, Elmquist JK, Nestler EJ, Lutter M (2010) A beta3-adrenergic-leptin-melanocortin circuit regulates behavioral and metabolic changes induced by chronic stress. Biol Psychiatry 67(11): 1075-1082 Covington JD, Tam CS, Bajpeyi S, Galgani JE, Noland RC, Smith SR, Redman LM, Ravussin E (2016) Myokine Expression in Muscle and Myotubes in Response to Exercise Stimulation. Med Sci Sports Exerc 48(3): 384-390 Crunkhorn S (2018) Metabolic disease: Safely mimicking c...

Circulating Myonectin and Irisin Levels in Gestational Diabetes Mellitus – A Case-control Study

“…This situation can be considered as valid for GDM, whose pathophysiology is comparable to T2DM. It is well-documented that exercise and stress training have favorable effects on glucose homeostasis through myonectin expression [ 24 ] . A study that assessed serum myonectin levels in T2DM and obese patients revealed that the myo nectin level was lower among T2DM and obese patients [ 13 ] .…”