ArticleAmerican journal of physiology. Endocrinology and metabolism2018
Nonalcoholic fatty liver disease and gastric bypass surgery regulate serum and hepatic levels of pyruvate kinase isoenzyme M2.
Article in American journal of physiology. Endocrinology and metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Myeloid HDAC7 drives liver inflammation and systemic glucose dysregulation during diet-induced obesity.Clinical & translational immunology · 2026Article
- Smilax glabra flavonoids ameliorate non-alcoholic steatohepatitis by regulating PKM2-dependent glycolysis and suppressing AIM2 inflammasome activation.Frontiers in immunology · 2026Article
- Pyruvate Kinase M2 Links Metabolism and Epigenetics: A New Target for Liver Disease Treatment.Biomolecules · 2025Review
- MicroRNA-122 regulates inflammatory and autophagic proteins by downregulating pyruvate kinase M2 in non-alcoholic fatty liver disease.Molecular and cellular biochemistry · 2025Article
- Association between TyG-related parameters and NAFLD risk in Japanese non-obese population.Scientific reports · 2025Article
- Contribution of Sex Differences to the Development of Cardiovascular Disease in Metabolic-Associated Steatotic Liver Disease (MASLD).International journal of translational medicine (Basel, Switzerland) · 2024Article
- Glycolysis in Chronic Liver Diseases: Mechanistic Insights and Therapeutic Opportunities.Cells · 2023Review
- DRAM1 increases the secretion of PKM2-enriched EVs from hepatocytes to promote macrophage activation and disease progression in ALD.Molecular therapy. Nucleic acids · 2022Article
- Covalent Inhibition of Pyruvate Kinase M2 Reprograms Metabolic and Inflammatory Pathways in Hepatic Macrophages against Non-alcoholic Fatty Liver Disease.International journal of biological sciences · 2022Article
- Pyruvate Kinase, Inflammation and Periodontal Disease.Pathogens (Basel, Switzerland) · 2021Review
- The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs.International journal of molecular sciences · 2021Review
- Pyruvate kinase M2: A simple molecule with complex functions.Free radical biology & medicine · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Treatment of nonalcoholic fatty liver disease (NAFLD) focuses on the underlying metabolic syndrome, and Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective options. In rodents and human patients, RYGB induces an increase in the gene and protein expression levels of the M2 isoenzyme of pyruvate kinase (PKM2) in the jejunum. Since PKM2 can be secreted in the circulation, our hypothesis was that the circulating levels of PKM2 increase after RYGB. Our data, however, revealed an unexpected finding and a potential new role of PKM2 for the natural history of metabolic syndrome and NAFLD. Contrary to our initial hypothesis, RYGB-treated patients had decreased PKM2 blood levels compared with a well-matched group of patients with severe obesity before RYGB. Interestingly, PKM2 serum concentration correlated with body mass index before but not after the surgery. This prompted us to evaluate other potential mechanisms and sites of PKM2 regulation by the metabolic syndrome and RYGB. We found that in patients with NAFLD and nonalcoholic steatohepatitis (NASH), the liver had increased PKM2 expression levels, and the enzyme appears to be specifically localized in Kupffer cells. The study of murine models of metabolic syndrome and NASH replicated this pattern of expression, further suggesting a metabolic link between hepatic PKM2 and NAFLD. Therefore, we conclude that PKM2 serum and hepatic levels increase in both metabolic syndrome and NAFLD and decrease after RYGB. Thus, PKM2 may represent a new target for monitoring and treatment of NAFLD.
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