Although GPCRs and their downstream pathways have been studied in various indications, with regard to mimicking exercise, a single receptor is unlikely to bring about the myriad metabolic adaptations and the consequent benefits. Many different G protein–coupled receptors (GPCRs), which represent the largest (~800) group of receptors, recognize a mixture of external molecules ( 12). Myofibers may recognize environmental changes through cell-surface receptors and reprogram the fiber type. Therefore, it is crucial to identify the signaling node that converts the external environmental changes to cellular metabolic control. Signaling molecule levels fluctuate respectively, and each of them binds to specific receptor(s) to transmit a mixture of cell-surface signals. In addition to the numerous exogenous stimuli introduced into the bloodstream, many endogenous ligands are secreted from other organs such as the gut, liver, adipose tissue, and brain. However, the vast majority of signals come from outside the cell. Previous identification of exercise-mimetic regulators mainly focused on intrinsic triggers such as ATP turnover and redox balance. As a result, mice ectopically overexpressing certain proteins (e.g., PGC1α) have been reported to have an endurance skeletal muscle phenotype, although many of them conversely exhibit increased adiposity with insulin resistance on a whole-body level ( 7, 11). Studies using transgenic mice ( 6– 8) or pharmacological agents ( 9, 10) have ignited interest in developing exercise mimetics. Hence, identifying the molecules or components responsible for reprogramming the myofiber phenotype can have a profound impact on the understanding of muscle dysfunction and the consequent pathophysiology of metabolic diseases. In contrast, individuals suffering from obesity or type 2 diabetes mellitus have fewer oxidative myofibers ( 2– 5). Reprogramming of myofiber types alters overall metabolic capacity endurance exercise training is linked to an increase in oxidative fibers, along with mitochondrial respiration and fatty acid oxidation ( 1). They differ with respect to their metabolic properties and are interconvertible. Mammalian skeletal muscles are composed of a mixture of oxidative and nonoxidative myofiber types. Skeletal muscle is a major contributor to systemic energy homeostasis because of its large mass relative to other tissues and its high rate of fuel consumption.
Our results define Gα13 as a switch regulator of myofiber reprogramming, implying that modulations of Gα13 and its downstream effectors in skeletal muscle are a potential therapeutic approach to treating metabolic diseases. Consequently, Gα13 ablation in muscles enhanced whole-body energy metabolism and increased insulin sensitivity, thus affording protection from diet-induced obesity and hepatic steatosis. Ser243 phosphorylation of NFATc1 was reduced after exercise, but was higher in obese animals. Mechanistically, Gα13 and its downstream effector RhoA suppressed nuclear factor of activated T cells 1 (NFATc1), a chief regulator of myofiber conversion, by increasing Rho-associated kinase 2–mediated (Rock2-mediated) phosphorylation at Ser243. Here, we show that muscle-specific ablation of Gα13 in mice promotes reprogramming of myofibers to the oxidative type, with resultant increases in mitochondrial biogenesis and cellular respiration. Heterotrimeric G proteins converge signals from cell-surface receptors to potentiate or blunt responses against environmental changes. I have also started taking Evamil spray and progesterone pills daily about a month ago, after blood tests determined a hormonal imbalance.Skeletal muscle is a key organ in energy homeostasis owing to its high requirement for nutrients. This was discovered after having an ultrasound and biopsy prior to the XXXXXXX sure ablation procedure. My periods were not significantly heavy, as many of the women I have read have this procedure performed, but very erratic, and my body was in a constant state of pre period bloating, due to discovering I have a “fluffy” uterine lining. My periods have been running as often as every two weeks, up to every 6 or 7 weeks throughout the year. I am 46 years old and have been experiencing very erratic periods the last year or so, thus prompting me to go to an OBGYN. I have read quite a few postings of women of all ages experiencing weight gain ( some significant ) after having the XXXXXXX sure procedure performed, and I would like to know, firstly, what would cause this weight gain, and secondly, if I could possibly expect to incur this weight gain in the future. Question: I had a XXXXXXX sure endometrial ablation procedure performed last Friday, and have some concerns about possible weight gain post procedure.