Emerging role of α-Klotho in energy metabolism and cardiometabolic diseases

Liu, Yuanbin; Chen, Mingkai

doi:10.1016/j.dsx.2023.102854

Cited by 5 publications

(3 citation statements)

References 159 publications

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“…In addition to IL-10, another protein with anti-inflammatory, antioxidant, and anticancer properties involved in cancer biology is known as Klotho [45]. Initially characterized as an anti-aging protein, particularly in the context of kidney function [46], Klotho has since been associated with various age-related diseases, including cardiovascular, renal, musculoskeletal, and neurodegenerative conditions [47,48]. It is noteworthy that an increasing body of research has highlighted the potential role of Klotho in cancer biology [45], as both cancer and aging share underlying pathophysiological mechanisms, such as the time-dependent accumulation of DNA damage, genomic instability, increased mutagenesis, and reduced levels of Klotho [45,48,49].…”

Section: Discussionmentioning

confidence: 99%

Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy

Pires,

Brandão-Rangel,

Silva-Reis

et al. 2024

Nutrients

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Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the overproduction of white blood cells, leading to symptoms such as fatigue, infections, and other complications. CML patients must take measures to prevent infections to mitigate the exacerbation of cancer cell proliferation and comorbidities. Methods: This study investigated whether vitamin C can suppress the hyperinflammatory activation of K-562 cells induced by lipopolysaccharide (LPS) and whether purinergic signaling (ATP and P2X7 receptor) and autophagy play a role in it. Two different doses of vitamin C (5 µg/mL and 10 µg/mL) were employed, along with the lysosome inhibitor chloroquine (CQ; 100 µM), administered 2 h prior to LPS stimulation (10 ng/mL) for a duration of 22 h in K-562 cells (3 × 105 cells/mL/well). Results: Both doses of vitamin C reduced the release of interleukin-6 (IL-6) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and tumor necrosis factor (TNF) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) induced by LPS. Furthermore, in LPS + CQ-stimulated cells, vitamin C at a concentration of 10 µg/mL inhibited the expression of LC3-II (p < 0.05). Conversely, both doses of vitamin C led to the release of the anti-inflammatory cytokine interleukin-10 (IL-10) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01), while only the 10 µg/mL dose of vitamin C induced the release of Klotho (10 µg/mL, p < 0.01). In addition, both doses of vitamin C reduced the accumulation of ATP (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and decreased the expression of the P2X7 receptor at the mRNA level. Conclusions: Vitamin C inhibits the hyperinflammatory state induced by LPS in K-562 cells, primarily by inhibiting the ATP accumulation, P2X7 receptor expression, and autophagy signaling.

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Section: Discussionmentioning

confidence: 99%

Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy

Pires,

Brandão-Rangel,

Silva-Reis

et al. 2024

Nutrients

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“…It comprises three isoforms: α-Klotho, β-Klotho and γ-Klotho. These isoforms have different tissue expression patterns and biological functions 7 . α-Klotho is mainly found in the renal tubular epithelium, choroid plexus in the brain, and secreted in the blood 8 .…”

Section: Introductionmentioning

confidence: 99%

“…α-Klotho is mainly found in the renal tubular epithelium, choroid plexus in the brain, and secreted in the blood 8 . It has been shown to act as a co-receptor for FGF 23, which helps to regulate calcium and phosphorus metabolism 7 . Studies have shown that α-Klotho inhibits insulin signaling 9 , regulates glucose and fat metabolism 10 and plays a role in the central regulation of energy balance 11 .…”

Section: Introductionmentioning

confidence: 99%

Serum α-Klotho and fibroblast growth factor 23 levels are not associated with non-proliferative diabetic retinopathy in type 1 diabetes mellitus

Oner,

Dogan,

Tuzun

et al. 2024

Sci Rep

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Diabetic retinopathy is a commonly observed cause of blindness and is a common problem in individuals with diabetes. Recent investigations have showed the capability of serum α-Klotho and FGF 23 in mitigating the effects of diabetic retinopathy. This study aimed to discover the correlation between FGF 23, α-Klotho, and diabetic retinopathy in type 1 diabetics. This case–control study included 63 diabetic patients and 66 healthy controls. Following an overnight duration of fasting, morning blood samples were taken from both the patient and the control groups. The serum concentrations of α-Klotho and FGF 23 were quantified. An experienced ophthalmologist inspected the retinopathy. All participants in this study have moderate non-proliferative retinopathy. A p value under 0.05 was considered statistically significant. The mean α-Klotho level for retinopathic diabetic patients was 501.7 ± 172.2 pg/mL and 579.6 ± 312.1 pg/mL for non-retinopathic diabetic patients. In comparison, α-Klotho level of the control group was 523.2 ± 265.4 pg/mL (p = 0.531). The mean of FGF 23 level did not demonstrate a significant difference (p = 0.259). The mean FGF 23 level were 75.7 ± 14.0 pg/mL, 74.0 ± 14.8 pg/mL and 79.3 ± 14.4 pg/mL in groups, respectively. In conclusion, there was no significant difference in FGF 23 and α-Klotho levels between type 1 diabetics with and without retinopathy when compared to the control group.

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Association between the triglyceride–glucose index and serum soluble Klotho in middle-aged and older adults from NHANES 2007–2016

Lai,

Chen

2024

Sci Rep

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Klotho, an anti-aging protein, is believed to participate in metabolic diseases and play a potential protective role by regulating insulin sensitivity. This study aimed to explore the relationship between the triglyceride-glucose (TyG) index (a simple marker of insulin resistance) and serum soluble Klotho (S-Klotho) levels. The cross-sectional study comprised 5237 adults aged 40-79 years who participated in the National Health and Nutrition Examination Surveys (NHANES) 2007-2016. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The serum levels of S-Klotho were measured by enzyme-linked immunosorbent assay. The association between the TyG index and S-Klotho levels was investigated by multiple linear regression models, smoothed curve fitting, segmented linear regression models, subgroup analyses, and interaction tests. The TyG index was inversely associated with serum S-Klotho level after full adjustment (β = − 45.11, 95% CI (− 79.53, − 10.69), P = 0.011). Furthermore, we also found a non-linear correlation and saturation phenomenon between the TyG index and serum S-Klotho levels, with a turning point of 9.56. In addition, a significant interaction effect of sex was found between the two (P for interaction < 0.001), with a more pronounced association observed in females. Further studies are required to explore the mechanisms and verify the correlation.

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Emerging role of α-Klotho in energy metabolism and cardiometabolic diseases

Cited by 5 publications

References 159 publications

Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy

Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy

Serum α-Klotho and fibroblast growth factor 23 levels are not associated with non-proliferative diabetic retinopathy in type 1 diabetes mellitus

Association between the triglyceride–glucose index and serum soluble Klotho in middle-aged and older adults from NHANES 2007–2016

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