Perimenopause Decreases SERCA2a Activity in the Hearts of a Mouse Model of Ovarian Failure.

Risk of cardiovascular disease mortality rises in women after menopause. While increased cardiovascular risk is largely attributed to postmenopausal declines in estrogens, the molecular changes in the heart that contribute to risk are poorly understood. Disruptions in intracellular calcium handling develop in ovariectomized mice and have been implicated in cardiac dysfunction.

Creatine and low-dose lithium supplementation separately alter energy expenditure, body mass, and adipose metabolism for the promotion of thermogenesis.

Nutraceutical approaches to promote adipose tissue thermogenesis may help to prevent obesity onset. Creatine is a critical regulator of adipose metabolic function and low-dose lithium supplementation has been shown to promote adipose thermogenesis. In the present study, we sought to directly compare the two supplements for their effects on adipose metabolism and thermogenesis.

Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB.

That uncoupling protein 1 (UCP1) is the sole mediator of adipocyte thermogenesis is a conventional viewpoint that has primarily been inferred from the attenuation of the thermogenic output of mice genetically lacking Ucp1 from birth (germline Ucp1). However, germline Ucp1 mice harbor secondary changes within brown adipose tissue. To mitigate these potentially confounding ancillary changes, we constructed mice with inducible adipocyte-selective Ucp1 disruption.

Toward countering muscle and bone loss with spaceflight: GSK3 as a potential target.

We examined the effects of ∼30 days of spaceflight on glycogen synthase kinase 3 (GSK3) content and inhibitory serine phosphorylation in murine muscle and bone samples from four separate missions (BION-M1, rodent research [RR]1, RR9, and RR18). Spaceflight reduced GSK3β content across all missions, whereas its serine phosphorylation was elevated with RR18 and BION-M1. The reduction in GSK3β was linked to the reduction in type IIA fibers commonly observed with spaceflight as these fibers are particularly enriched with GSK3.

Measuring SERCA-mediated calcium uptake in mouse muscle homogenates.

This protocol employs the indo-1 Ca fluorophore to quantify Ca uptake by the sarco(endo)plasmic reticulum Ca ATPase pump in murine muscle homogenates and allows for real-time kinetic measurement of Ca mobilization within the muscle homogenate. This protocol can be easily adapted for other tissue types and can be modified to single-emission/single-excitation Ca dyes. Fitted to a 96-well plate, this assay can be readily performed in most laboratories with minimal sample requirement and the option of multiple replicates.

Erratum: Corringendum: The effects of neurogranin knockdown on SERCA pump efficiency in soleus muscles of female mice fed a high fat diet.

[This corrects the article DOI: 10.3389/fendo.2022.

Low-dose lithium supplementation promotes adipose tissue browning and sarco(endo)plasmic reticulum Ca ATPase uncoupling in muscle.

Sarco(endo)plasmic reticulum Ca-ATPase (SERCA) uncoupling in skeletal muscle and mitochondrial uncoupling via uncoupling protein 1 (UCP1) in brown/beige adipose tissue are two mechanisms implicated in energy expenditure. Here, we investigated the effects of glycogen synthase kinase 3 (GSK3) inhibition via lithium chloride (LiCl) treatment on SERCA uncoupling in skeletal muscle and UCP1 expression in adipose. C2C12 and 3T3-L1 cells treated with LiCl had increased SERCA uncoupling and UCP1 protein levels, respectively, ultimately raising cellular respiration; however, this was only observed when LiCl treatment occurred throughout differentiation.

Sarco(endo)plasmic reticulum Ca-ATPase function is impaired in skeletal and cardiac muscles from young DBA/2J mdx mice.

The DBA/2J (D2) mouse is a more severe model of Duchenne muscular dystrophy when compared to the traditional C57BL/10 (C57) mouse. Here, we questioned whether sarco(endo)plasmic reticulum Ca-ATPase (SERCA) function would differ in muscles from young D2 and C57 mice. Both D2 and C57 mice exhibited signs of impaired Ca uptake in the gastrocnemius, diaphragm, and left ventricle; however, the level of impairment was more severe in D2 mice.

The effects of neurogranin knockdown on SERCA pump efficiency in soleus muscles of female mice fed a high fat diet.

The sarco(endo)plasmic reticulum Ca ATPase (SERCA) pump is responsible for the transport of Ca from the cytosol into the sarcoplasmic reticulum at the expense of ATP, making it a regulator of both muscle relaxation and muscle-based energy expenditure. Neurogranin (Ng) is a small protein that negatively regulates calcineurin signaling. Calcineurin is Ca/calmodulin dependent phosphatase that promotes the oxidative fibre type in skeletal muscle and regulates muscle-based energy expenditure.

Heterozygous SOD2 deletion selectively impairs SERCA function in the soleus of female mice.

The sarco(endo)plasmic reticulum Ca ATPase (SERCA) restores intracellular Ca ([Ca ] ) to resting levels after muscle contraction, ultimately eliciting relaxation. SERCA pumps are highly susceptible to tyrosine (T)-nitration, impairing their ability to take up Ca resulting in reduced muscle function and increased [Ca ] and cellular damage. The mitochondrial antioxidant enzyme, superoxide dismutase 2 (SOD2), converts superoxide radicals into less reactive H O .

Characterizing SERCA Function in Murine Skeletal Muscles after 35-37 Days of Spaceflight.

It is well established that microgravity exposure causes significant muscle weakness and atrophy via muscle unloading. On Earth, muscle unloading leads to a disproportionate loss in muscle force and size with the loss in muscle force occurring at a faster rate. Although the exact mechanisms are unknown, a role for Ca dysregulation has been suggested.

Neuronatin promotes SERCA uncoupling and its expression is altered in skeletal muscles of high-fat diet-fed mice.

Neuronatin (NNAT) is a transmembrane protein in the endoplasmic reticulum involved in metabolic regulation. It shares sequence homology with sarcolipin (SLN), which negatively regulates the sarco(endo)plasmic reticulum Ca -ATPase (SERCA) that maintains energy homeostasis in muscles. Here, we examined whether NNAT could uncouple the Ca transport activity of SERCA from ATP hydrolysis, similarly to SLN.

Neuronatin regulates whole-body metabolism: is thermogenesis involved?

Neuronatin (NNAT) was originally discovered in 1995 and labeled as a brain developmental gene due to its abundant expression in developing brains. Over the past 25 years, researchers have uncovered NNAT in other tissues; notably, the hypothalamus, pancreatic β-cells, and adipocytes. Recent evidence in these tissues indicates that NNAT plays a significant role in metabolism whereby it regulates food intake, insulin secretion, and adipocyte differentiation.