mProX™ Human HCAR1 Stable Cell Line

Talarico GGM, et al. "Lactate signaling and fuel selection in rainbow trout: Mobilization of energy ." American journal of physiology. Regulatory, integrative and comparative , 2023.
The lipolytic rate, also known as the rate of appearance of glycerol in the circulation (R(a) glycerol), and hepatic glucose production (R(a) glucose) are important measurements for analyzing metabolic processes in rainbow trout. Additionally, the involvement of certain tissue proteins in lactate signaling, glucose transport, glycolysis, gluconeogenesis, lipolysis, and beta-oxidation were studied. Results indicate that while lactate does not affect lipolysis in the same way as in mammals (with R(a) glycerol remaining at 7.3 +/- 0.5 micromol kg(-1) min(-1)), it does significantly decrease hepatic glucose production (16.4 +/- 2.0 to 8.9 +/- 1.2 micromol kg(-1) min(-1)). This reduction is linked to a decrease in PCK1 activity (with a 60% decrease in gene expression and 24% decrease in protein level), as well as the substitution of lactate for glucose as a fuel source in most tissues, except white muscle, which increases glut4a expression. It is also noted that rainbow trout do not activate HCAR1 signaling in response to hyperlactatemia, as seen in unchanged or repressed gene expression of the receptor in red muscle. Ultimately, this study highlights important functional differences in HCAR1 signaling between fish and mammals, specifically in the regulation of fuel selection.
Pubmed: 37694336   DOI: 10.1152/ajpregu.00033.2023

Huang YF, et al. "Lactate-upregulated NADPH-dependent NOX4 expression via HCAR1/PI3K pathway ." Redox biology, 2023.
Recent research suggests that metabolic factors play a key role in the development and progression of osteoarthritis (OA). One such factor is lactate, which has been shown to contribute to disease onset and progression. However, the mechanism by which lactate affects chondrocyte function in OA remains unclear. This study aimed to confirm whether serum lactate levels were elevated in OA patients and to explore its potential role in chondrocyte damage. The findings revealed a positive correlation between lactate levels and markers of metabolic dysfunction, such as fasting blood glucose and lipids, in OA patients. Additionally, treatment with lactate was found to activate both the lactate receptor HCAR1 and lactate transporters in human chondrocytes. Our study revealed that lactate serves a dual function, enhancing NADPH levels through the pentose phosphate pathway and activating the PI3K/Akt signaling pathway via HCAR1 to up-regulate NADPH oxidase 4 (NOX4). This ultimately leads to the generation of reactive oxygen species (ROS) and contributes to chondrocyte damage, as evidenced by increased expression of catabolic enzymes, inflammation markers, and cellular aging. However, pre-treatment with the ROS scavenger N-Acetyl-l-cysteine (NAC) was able to reverse the damaging effects of lactate on chondrocytes. Notably, in vivo experiments using a rat model demonstrated that intra-articular injection of lactate exacerbated cartilage damage and accelerated the progression of OA, which could be attenuated by treatment with the NOX4 inhibitor GLX351322. This study highlights the role of lactate as a metabolic factor in the pathogenesis of OA and provides a basis for potential metabolic-based therapies for the disease.
Pubmed: 37688977   DOI: 10.1016/j.redox.2023.102867