Limited effects of systemic or renal lipoprotein lipase deficiency on renal physiology and diseases.

Yoshihiko Fujino, Mako Yasuda-Yamahara, Yuki Tanaka-Sasaki, Shogo Kuwagata, Kosuke Yamahara, Atsuko Tagawa, Masami Chin-Kanasaki, Motoko Yanagita, Hiroshi Maegawa, Shinji Kume

Biochemical and biophysical research communications 2022 Sep 10

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Lipoprotein lipase (LPL) is an enzyme that catalyzes the hydrolysis of circulating triglyceride and the transport of fatty acids into cells. Its activity is positively regulated by insulin, and insulin resistance is associated with low LPL activity and subsequent hypertriglyceridemia. The involvement of hypertriglyceridemia in chronic kidney disease (CKD) is still under the debate in a clinical setting. Therefore, we aimed to study the role of hypertriglyceridemia in the disease using mice with systemic or renal-specific LPL deficiency. Systemic LPL deficiency was characterized by hypertriglyceridemia, but not renal injury or dyslipidemia-related conditions, such as fatty liver. Furthermore, the LPL deficiency-induced hypertriglyceridemia was not associated with a worsening of the CKD phenotype or atherosclerosis, even when CKD was induced by 5/6 nephrectomy. Next, because LPL-mediated fatty acid uptake may be important for energy metabolism in proximal tubular epithelial cells (PTECs), the role of renal LPL in renal physiology was studied by generating mice lacking LPL specifically in PTECs. These mice showed no abnormalities in their histology or renal reabsorption of micro molecules. These findings suggest that systemic and renal lipid abnormalities caused by LPL deficiency do not cause or worsen the development of renal injury, and provide novel insight regarding the potential role of lipotoxicity in the pathogenesis of obesity-related kidney injury. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Yoshihiko Fujino, Mako Yasuda-Yamahara, Yuki Tanaka-Sasaki, Shogo Kuwagata, Kosuke Yamahara, Atsuko Tagawa, Masami Chin-Kanasaki, Motoko Yanagita, Hiroshi Maegawa, Shinji Kume. Limited effects of systemic or renal lipoprotein lipase deficiency on renal physiology and diseases. Biochemical and biophysical research communications. 2022 Sep 10;620:15-20