Low‐dose lithium supplementation augments mitochondrial biogenesis in murine skeletal muscle after high fat feeding
Bibliographic record
Abstract
Promotion of oxidative metabolism in skeletal muscle improves muscle performance, fatigue resistance, and may help combat the obesogenic effects of a high fat diet. Lithium is a well‐known glycogen synthase kinase (GSK3) inhibitor and we have recently shown that low‐dose lithium supplementation (10 mg kg ‐1 day ‐1 ) augments skeletal muscle oxidative capacity in mice. In the soleus muscle, lithium mediated GSK3 inhibition increased the expression of oxidative markers such as peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1a) and myosin heavy chain I (MHCI) leading to improvements in muscle contractility and fatigue resistance. Interestingly, this same dose of lithium (10 mg kg ‐1 day ‐1 ) has been previously shown to attenuate high fat diet induced weight gain and metabolic efficiency (weight gained per calories consumed). However, the impact of lithium supplementation on muscle oxidative phenotype after high fat feeding has yet to be investigated. In this study, 36 wild‐type male C57BL/6J mice were randomly assigned to low‐fat standard chow diet (LFD, 4% kcal fat), high‐fat diet (HFD, 60% kcal fat), or HFD with lithium chloride (HFD + Li; 10 mg kg ‐1 day ‐1 ) treatment groups for 12 weeks. Soleus muscles were collected at the end for Western blot analysis of total and phosphorylated GSK3 (inhibitory sites serine9 for GSK3b and serine21 for GSK3a), PGC‐1a, cytochrome c oxidase subunit IV (COXIV), and MHCI protein content. Our results showed that the level of phosphorylated GSK3a and GSK3b (relative to total GSK3) were significantly lower after the HFD (‐41 and ‐44%, respectively, p < 0.05), but in the HFD + Li group levels were similar to the LFD group. Therefore, the HFD enhanced soleus muscle GSK3 activation, and lithium supplementation was able to reduce this effect. No significant changes in MHCI content were observed. When examining PGC‐1a, we found that the HFD + Li group had protein levels that were nearly 2‐fold higher vs LFD, albeit only trending towards significance ( p = 0.06). Further, COXIV content progressively increased from LFD, to HFD, and to HFD + Li (linear trend, r 2 =0.26, p = 0.002) with both HFD and HFD + Li groups having significantly higher COXIV content when compared to LFD. Altogether, our data shows that GSK3 inhibition via low dose lithium supplementation can augment mitochondrial biogenesis in the presence of a HFD. Future studies will further examine whether GSK3 inhibition via lithium can augment muscle oxidative metabolism after high fat feeding.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".