In conclusion LA is able

In conclusion, LA is able to enhance osteoblast differentiation that mediated by PTH in a MCT-1 independent but GPR81 signaling dependent manner. This increase requires p38 activation and an Akt activation that depended on Gβγ-protein-PLC-PKC signaling. However, the ability of LA to increase PTH–mediated osteoblast differentiation should be reproduced in vivo. These data provide fundamental insight into how bone microenvironments, especially in physiological or pathological conditions that with LA production, can greatly alter osteoblast responses to bone inducing factors. Given our expanding comprehension of myriad activities played by LA and osteoblast, understanding and intervening in these signaling cascades is likely to be clinically important.
Acknowledgements This work was supported by the National Natural Science Foundation of China (81670808, 81541103), Natural Science Foundation of Jiangsu Province (Basic Research Program, BK20161136) to Yu Wu. Miaomiao Wang received the support from the National Natural Science Foundation of China (81602833).Yu Wu received the intramural funding from the Jiangnan University Science Research Program (JUSRP115A32, JUPH201503 and JUSRP51710A). This work was partially supported by national first-class displine program of Food Science and Technology (JUFSTR20180101).
Introduction Lactate is produced from glucose through glycolysis and the conversion of pyruvate by lactate dehydrogenase (Meyerhof and Kiessling, 1935). It serves as a precursor for hepatic gluconeogenesis and may also be an energy substrate for aerobic oxidation via the citric Fmoc-Cl cycle in various peripheral tissues (Brooks, 2002, Kreisberg, 1980). The role of lactate in the delivery of oxidative and gluconeogenic substrates is described by the “lactate shuttle” concept (Brooks, 2009). The skeletal muscle is regarded as the major site of lactate production. While it forms and utilizes lactate continuously under resting conditions, lactate formation increases during exercise (Bergman et al., 1999, Margaria et al., 1933). Also, the adipose tissue is an important source for lactate (Crandall et al., 1983, DiGirolamo et al., 1992, Ellmerer et al., 1998, Jansson et al., 1990, Marin et al., 1987). It can convert more than 50% of the metabolized glucose to lactate, a process stimulated by insulin and glucose uptake (Coppack et al., 1989, Hagstrom et al., 1990, Henry et al., 1996, Jansson et al., 1994, Qvisth et al., 2007). The major role of the adipose tissue is to store energy in the form of triglycerides, which are constantly turned over by lipolysis and re-esterification (Duncan et al., 2007, Wang et al., 2008). Net lipolysis increases when energy demands are high and insulin levels are low, for example, during mild and intermediate exercise as well as during fasting, while it decreases postprandially after energy uptake. The second messenger cyclic AMP (cAMP) plays an important role in the regulation of lipolysis, as it can activate lipolytic enzymes via stimulation of the cAMP-dependent kinase (Langin, 2006, Zechner et al., 2005). During exercise and starvation, activation of β-adrenergic receptors induces lipolysis through the activation of cAMP formation by adenylyl cyclase, a process mediated by the G protein Gs (Horowitz, 2003, Ros et al., 1989). Insulin is the major hormone exerting an antilipolytic effect in the fed state. Its action is mediated by phosphatidylinositoI-3-kinase (PI-3-kinase)-dependent activation of phosphodiesterase 3B (PDE3B) resulting in an increased rate of cAMP degradation (Degerman et al., 1998, Duncan et al., 2007, Langin, 2006). Several other antilipolytic regulators like adenosine, prostaglandin E2, neuropeptide Y, 3-hydroxy-butyrate, or the antidyslipidemic drug nicotinic acid act through Gi-coupled receptors, resulting in an inhibition of cAMP formation via adenylyl cyclase (Gille et al., 2008, Granneman and Moore, 2008, Langin, 2006, Wang et al., 2008).