α-Klotho, a known anti-aging
protein, exerts diverse physiological effects including: maintenance of
phosphate and
calcium homeostasis, modulation of cell proliferation, and enhanced buffering of
reactive oxygen species. However, the role of α-Klotho in the regulation of energy metabolism is complex and poorly understood. Here we investigated the effects of 5 weeks peripheral administration of α-Klotho in high fat diet induced obese mice. Food intake,
blood glucose, and
body weight were measured daily. Energy expenditure was determined with indirect calorimetry and body composition with magnetic resonance imaging. Liver and adipose tissue were collected for
lipid content measurements and gene expression analysis. α-Klotho-treated mice experienced reduced adiposity, increased lean mass, and elevated energy expenditure, despite no changes in food intake,
body weight, or fed
blood glucose levels.
Lipid accumulation in liver and adipose tissue was also reduced compared to controls. Furthermore, Real-time quantitative PCR showed reduced expression of key lipogenic genes in α-Klotho treated mice in these organs. Taken together, these data suggest encouraging therapeutic potential of α-Klotho and highlight a need for further research into the specific mechanisms explaining improved body composition, elevated energy expenditure, and reduced
lipid content in both liver and adipose tissue in α-Klotho-treated mice.