Low-dose lithium supplementation promotes adipose tissue browning and sarco(endo)plasmic reticulum Ca2+ ATPase uncoupling in muscle

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

“…And contrasts with the study by Geromella et al. 36 which observed a consistent increase in mitochondrial proteins, including UCP1, and multilocular phenotype in WAT with low-dose lithium supplementation. The difference in results is likely due to model differences as the present study was done in rats compared to a mouse model used in the previous study.…”

“…Similar uncoupling and upregulation of SERCA uncouplers was observed in muscle-specific GSK3 knockdown mice. 36 In the present study we examined SERCA coupling along with the protein expression of known uncouplers and contributors to SERCA-dependent thermogenesis including GSK3, RYR, SLN, and NNAT. None of the previous markers of muscle nonshivering thermogenesis were altered with lithium supplementation ( Figure S1 ) and may be dissimilar to previous results due to the utilization of a different rodent model and dosing than was used previously.…”

“… 25 Similarly, the serum concentration of lithium in the present study is unknown but is expected to be ∼0.1 mM based on previous literature, which is far below typical therapeutic values of ∼1.2 mM 45 and is similar to studies that show thermogenic potential for lithium. 36 Furthermore it is unknown if the sex-specificity of the findings are estrogen-dependent or are resultant of another mechanism. It is of critical importance to determine how to overcome sex-dependent mechanistic differences to promote optimal supplementation protocols for both sexes.…”

GSK3 inhibition improves skeletal muscle function and whole-body metabolism in the severe DBA/2Jmdxmouse model

“…DBA/2J (D2)- mdx (stock #001801) and D2 WT (stock #000671) were ordered from Jackson Laboratories at 5-6 weeks of age. Muscle-specific GSK3 KD mice were generated in our lab using cryorecovered GSK3 a and β floxed mice 81 . All mice were housed in Brock University’s Animal Facility, in an environmentally controlled room with a standard 12:12 hour light-dark cycle and allowed access to food and water ad libitum .…”

“…Insulin tolerance testing was performed as previously described 81 . Briefly, concentrations of blood glucose were determined by sampling blood from the tail vein at 0, 15, 30, 60, and 120 min following the IP insulin injection (0.5 U/kg) with the use of a hand-held glucometer (Freestyle Lite; Abbott).…”