Biochemical and Biophysical Research Communications
Regular ArticleDisruption of klotho Gene Causes an Abnormal Energy Homeostasis in Mice☆
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Cited by (57)
Emerging role of α-Klotho in energy metabolism and cardiometabolic diseases
2023, Diabetes and Metabolic Syndrome: Clinical Research and ReviewsCirculating α-klotho regulates metabolism via distinct central and peripheral mechanisms
2021, Metabolism: Clinical and ExperimentalCitation Excerpt :Approximately 24 years ago the α-klotho gene was discovered when a study revealed mutation of a single gene within Chromosome 13 results in a rapid, premature aging phenotype [1]. α-Klotho overexpression has since been researched for its ability to prolong the lifespan 20–30% in rodents [2], as well as its therapeutic potential in various neurological [3–7], metabolic [8–15], cardiorespiratory [16–25], osmolar, [26–29] and cancer-related diseases/disorders [30]. More recently, in an attempt to combat the unrelenting obesity and diabetes epidemics, studies have begun to elucidate the specific roles of α-klotho in the regulation of energy and substrate metabolism.
Soluble Klotho Improves Hepatic Glucose and Lipid Homeostasis in Type 2 Diabetes
2020, Molecular Therapy Methods and Clinical DevelopmentCitation Excerpt :sKL plays an important role in kidney diseases that involve hyperphosphatemia, vascular calcification, inflammation, and oxidative stress.10–12 Previous studies suggest that sKL is also linked to metabolic diseases, e.g., NASH and T2D, and the regulation of adipogenesis.13,14 In light of some studies, sKL may function as a circulating hormone that represses intracellular signals to mediate energy metabolism.13,15
Administration of alpha klotho reduces liver and adipose lipid accumulation in obese mice
2019, HeliyonCitation Excerpt :This encouraging therapeutic potential is supported by past literature observing beta cell specific α-Klotho overexpression to attenuate the progression of diabetes via improved insulin release and ROS buffering [6, 16, 21]. Furthermore, in α-Klotho deficient mice, non-shivering thermogenesis and gene expression of uncoupling protein 1 are impaired, while gluconeogenic gene expression in the liver is elevated [10]. However, the role of α-Klotho in the pathophysiology of metabolic disease is complex.
1,25-Dihydroxyvitamin D and Klotho: A Tale of Two Renal Hormones Coming of Age
2016, Vitamins and HormonesCitation Excerpt :Klotho knockout mice exhibit less energy storage and expenditure compared to wild-type mice (Mori et al., 2000), as well as attenuated insulin production and enhanced insulin sensitivity (Utsugi et al., 2000; Wolf et al., 2008). Apparently, klotho suppresses the downstream signaling pathways of both the insulin receptor (mediated by insulin receptor substrate (IRS)), and the insulin-like growth factor 1 receptor (IGF-1R), without directly associating with either of these receptors (Mori et al., 2000; Yamamoto et al., 2005). Instead, klotho likely affects IRS and IGF-1R activity via modulation of the forkhead box proteins (FOXOs).
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Abbreviations used: BAT, brown adipose tissue; WAT, white adipose tissue; PEPCK, phosphoenolpyruvate carboxykinase; UCP-1, uncoupling protein-1; BW, body weight.
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To whom correspondence should be addressed at Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Fax: +81-75-771 9452. E-mail: [email protected].