ArticleJournal of cachexia, sarcopenia and muscle2022
Extracellular lipidome change by an SGLT2 inhibitor, luseogliflozin, contributes to prevent skeletal muscle atrophy in db/db mice.
Article in Journal of cachexia, sarcopenia and muscle, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The Effects of SGLT2 Inhibitors on Muscle Health in Older Adults: A Systematic Review and Meta-Analysis.Pharmacology research & perspectives · 2026Pooled it
- Dapagliflozin modulates plasma lipidomic profile and urinary metabolite excretion in type 2 diabetes.Cardiovascular diabetology · 2025Trial
- Effects of Ipragliflozin on Skeletal Muscle Adiposity in Patients with Diabetes and Metabolic Dysfunction-associated Steatotic Liver Disease.Internal medicine (Tokyo, Japan) · 2025Trial
- Effects of empagliflozin alone and in combination with exercise on the soleus muscle in obese type 2 diabetic rats.The journal of physiological sciences : JPS · 2026Article
- Spatial-Bioenergetic-Immune Axis in Type 2 Diabetes Mellitus-Associated Sarcopenia: A Review from Pathogenesis to Targeted Reconstruction.Journal of inflammation research · 2026Review
- Redox Homeostasis in Metabolic Syndrome and Type II Diabetes: Role of Skeletal Muscle and Impact of Gold-Standard Treatments.International journal of molecular sciences · 2025Review
- Tofogliflozin ameliorates cardiotoxin induced skeletal muscle injury and fibrosis in obesity.Scientific reports · 2025Article
- Diabetes and Sarcopenia: Metabolomic Signature of Pathogenic Pathways and Targeted Therapies.International journal of molecular sciences · 2025Review
- Exploring the link between the ZJU index and sarcopenia in adults aged 20-59 using NHANES and machine learning.Scientific reports · 2025Article
- Changes in body composition and handgrip strength during dapagliflozin administration in patients with chronic kidney disease.Clinical kidney journal · 2025Article
- Linking the Planetary Health Diet Index to sarcopenia: the mediating effect of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR).Frontiers in nutrition · 2025Article
- SGLT2 inhibitor downregulates ANGPTL4 to mitigate pathological aging of cardiomyocytes induced by type 2 diabetes.Cardiovascular diabetology · 2024Article
- A multi-omics approach to overeating and inactivity-induced muscle atrophy in db/db mice.Journal of cachexia, sarcopenia and muscle · 2024Article
- Article
- SGLT2 inhibitors: a novel therapy for cognitive impairment via multifaceted effects on the nervous system.Translational neurodegeneration · 2024Review
- Article
- Treatment with dapagliflozin increases FGF-21 gene expression and reduces triglycerides content in myocardial tissue of genetically obese mice.Journal of endocrinological investigation · 2024Article
- RRM2 promotes the proliferation of chicken myoblasts, inhibits their differentiation and muscle regeneration.Poultry science · 2024Article
- MCC950 Ameliorates Diabetic Muscle Atrophy in Mice by Inhibition of Pyroptosis and Its Synergistic Effect with Aerobic Exercise.Molecules (Basel, Switzerland) · 2024Article
- The Current Landscape of Pharmacotherapies for Sarcopenia.Drugs & aging · 2024Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiabetes mellitus increases the excretion of urinary glucose from the renal glomeruli due to elevated blood glucose levels. In the renal tubules, SGLT2 is expressed and reabsorbs the excreted urinary glucose. In the pathogenesis of diabetes mellitus, glucose reabsorption by SGLT2 is increased, and SGLT2 inhibitors improve hyperglycaemia by inhibiting this reabsorption. When urinary glucose excretion is enhanced, glucose supply to skeletal muscle may be insufficient and muscle protein catabolism may be accelerated. On the other hand, SGLT2 inhibitors not only ameliorate hyperglycaemia but also improve fatty acid metabolism in muscle, which may prevent muscle atrophy.
methodsEight-week-old male db/m mice or db/db mice were fed a standard diet with or without the SGLT2i luseogliflozin (0.01% w/w in chow) for 8 weeks. Mice were sacrificed at 16 weeks of age, and skeletal muscle and serum lipidomes, as well as skeletal muscle transcriptome, were analysed.
resultsAdministration of SGLT2i led to not only decreased visceral fat accumulation (P = 0.004) but also increased soleus muscle weight (P = 0.010) and grip strength (P = 0.0001). The levels of saturated fatty acids, especially palmitic acid, decreased in both muscles (P = 0.017) and sera (P = 0.041) upon administration of SGLT2i, while the content of monosaturated fatty acids, especially oleic acid, increased in both muscle (P < 0.0001) and sera (P = 0.009). Finally, the accumulation of transcripts associated with fatty acid metabolism, such as Scd1, Fasn, and Elovl6, and of muscle atrophy-associated transcripts, such as Foxo1, Mstn, Trim63, and Fbxo32, decreased following SGLT2i administration.
conclusionsIntramuscular fatty acid metabolism and gene expression were influenced by the extracellular lipidome, which was modified by SGLT2i. Hence, secondary effects, other than the hypoglycaemic effects of SGLT2i, might lead to the alleviation of sarcopenia.
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