ArticleMolecular metabolism2020
Glycerol not lactate is the major net carbon source for gluconeogenesis in mice during both short and prolonged fasting.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
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- Metabolic control by liver-kidney crosstalk and glucagon in health and disease.Nature reviews. Nephrology · 2026Review
- The Gibbs free energy landscape based on liver metabolome revealed thermodynamic robustness against fasting and obesity.iScience · 2026Article
- Hepatic GAPDH prevents excessive fasting-induced steatosis via serine-dependent inhibition of diacylglycerol synthesis.Cell death and differentiation · 2026Article
- Regulation and clinical manifestations of gluconeogenesis dysfunction.npj metabolic health and disease · 2026Review
- Absence of Thioredoxin Domain Containing 5 Improves Glucose Tolerance and Insulin Sensitivity in Male Mice.International journal of molecular sciences · 2026Article
- Adiponectin exerts sex-dependent effects on lipid, amino acid, and glucose metabolism during caloric restriction.PLoS biology · 2026Article
- Insulin receptorNature communications · 2026Article
- Endocrine regulation of the hepatic fasting response: cues, cooperation and consequences.Nature reviews. Endocrinology · 2026Review
- Brown adipose tissue activity impacts systemic lactate clearance in male mice.The Journal of physiology · 2025Article
- Fasting-Induced Hepatic Gluconeogenesis Is Compromised In Anxa6Journal of cellular physiology · 2025Article
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- An organism-level quantitative flux model of energy metabolism in mice.Cell metabolism · 2025Article
- Postbiotic Impact on Host Metabolism and Immunity Provides Therapeutic Potential in Metabolic Disease.Endocrine reviews · 2025Review
- Glucose sensing and homeostasis by adipocyte GPCR.Frontiers in endocrinology · 2025Review
- Quantification of nutrient fluxes during acute exercise in mice.Cell metabolism · 2024Article
- In vivo glycerol metabolism in patients with glycerol kinase deficiency.JIMD reports · 2024Article
- Article
- Comprehensive quantification of metabolic flux during acute cold stress in mice.Cell metabolism · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveFasting results in major metabolic changes including a switch from glycogenolysis to gluconeogenesis to maintain glucose homeostasis. However, the relationship between the length of fasting and the relative contribution of gluconeogenic substrates remains unclear. We investigated the relative contribution of glycogen, lactate, and glycerol in glucose production of male C57BL/6 J-albino mice after 6, 12, and 18 h of fasting.
methodsWe used non-perturbative infusions of
resultsDuring infusion studies, both lactate and glycerol significantly label about 60% and 30-50% glucose carbon, respectively, but glucose labels much more lactate (∼90%) than glycerol carbon (∼10%). Our analyses indicate that lactate, but not glycerol is largely recycled during all fasting periods such that lactate is the largest direct contributor to GNG via the Cori cycle but a minor source of new glucose carbon (overall contribution). In contrast, glycerol is not only a significant direct contributor to GNG but also the largest overall contributor to GNG regardless of fasting length. Prolonged fasting decreases both the whole body turnover rate of glucose and lactate but increases that of glycerol, indicating that the usage of glycerol in GNG become more significant with longer fasting.
conclusionCollectively, these findings suggest that glycerol is the dominant overall contributor of net glucose carbon in GNG during both short and prolonged fasting.
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