ReviewMetabolism: clinical and experimental2021
Circulating α-klotho regulates metabolism via distinct central and peripheral mechanisms.
Review in Metabolism: clinical and experimental, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 47 citations in OpenAlex.
- Nuclear mitochondrial interaction test reveals sex-dependent mitochondrial SNP-Klotho interactions on diabetes risk.Journal of the Endocrine Society · 2026Article
- Serum FGF-23 and α-Klotho Levels in Prolactinoma and Non-Tumoral Hyperprolactinemia: An Exploratory Cross-Sectional Comparative Study.Diagnostics (Basel, Switzerland) · 2026Article
- Role of soluble alpha-klotho as a novel biomarker for characterizing children with autism spectrum disorder in Kurdistan, Iraq.World journal of clinical pediatrics · 2026Article
- Sex- and Age-Specific Inverted U-Shaped Links between Dietary Iron Intake and Serum α‑Klotho in Chinese Adults.Biological trace element research · 2026Article
- DNMT inhibitor ameliorates hyperglycemia and renal inflammation partially via reversing hypermethylation-induced Klotho suppression in diabetic mice.Clinical epigenetics · 2026Article
- Selective deletion of FGFR1 in AgRP neurons impairs energy homeostasis under high-fat diet in mice.Molecular metabolism · 2026Article
- Klotho-derived peptide 1 ameliorates hepatic fibrosis induced by αKlotho deficiency and liver injury.International journal of biological sciences · 2026Article
- Klotho deficiency and cognitive impairment in dialysis patients: mechanisms, clinical evidence, and therapeutic implications.Frontiers in aging neuroscience · 2026Review
- α-Klotho Supplementation Mitigates Cumulative Exercise-Induced Fatigue via Coordinated NRF2-Mediated Antioxidant Defense and AKT/GS-Driven Hepatic Glycogen Supercompensation in Mice.International journal of molecular sciences · 2025Article
- Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.MedComm · 2025Review
- The Association Between Weight-Adjusted-Waist Index and S-Klotho Levels in Adults: NHANES 2007-2016.Food science & nutrition · 2025Article
- Sex-specific association between serum α-klotho levels and sleep disturbances in the elderly: a cross-sectional study.European journal of medical research · 2025Article
- Association between serum α-klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: evidence from a Chinese cohort and the NHANES database.Diabetology & metabolic syndrome · 2025Article
- Central adiposity and α-klotho: inflammatory mechanisms underlying aging biomarkers related to body roundness index.Lipids in health and disease · 2025Article
- Association between serum α-Klotho levels and mortality in US adults with osteoporosis.BMC public health · 2025Article
- Unveiling the Emerging Role of Klotho: A Comprehensive Narrative Review of an Anti-aging Factor in Human Fertility.Current protein & peptide science · 2025Review
- Article
- The relationship of serum klotho levels and triglyceride glucose index-related indicators.Lipids in health and disease · 2024Article
- Systemic immune-inflammation mediates the association between Klotho protein and metabolic syndrome: findings from a large-scale population-based study.Lipids in health and disease · 2024Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Emerging evidence implicates the circulating α-klotho protein as a prominent regulator of energy balance and substrate metabolism, with diverse, tissue-specific functions. Despite its well-documented ubiquitous role inhibiting insulin signaling, α-klotho elicits potent antidiabetic and anti-obesogenic effects. α-Klotho facilitates insulin release and promotes β cell health in the pancreas, stimulates lipid oxidation in liver and adipose tissue, attenuates hepatic gluconeogenesis, and increases whole-body energy expenditure. The mechanisms underlying α-klotho's peripheral functions are multifaceted, including hydrolyzing transient receptor potential channels, stimulating integrin β1➔focal adhesion kinase signaling, and activating PPARα via inhibition of insulin-like growth factor receptor 1. Moreover, until recently, potential metabolic roles of α-klotho in the central nervous system remained unexplored; however, a novel α-klotho➔fibroblast growth factor receptor➔PI3kinase signaling axis in the arcuate nucleus of the hypothalamus has been identified as a critical regulator of energy balance and glucose metabolism. Overall, the role of circulating α-klotho in the regulation of metabolism is a new focus of research, but accumulating evidence identifies this protein as an encouraging therapeutic target for Type 1 and 2 Diabetes and obesity. This review analyzes the new literature investigating α-klotho-mediated regulation of metabolism and proposes impactful future directions to progress our understanding of this complex metabolic protein.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.