Key result
Stap1 loss fails to alter lipid profiles or metabolic parameters in western diet-fed mice.
Why the study?
Initial human studies suggested a potential relationship between STAP1 variants and autosomal dominant familial hypercholesterolemia, but subsequent studies have been contradictory.
Stap1 loss yields no lipid phenotype in mice; leaves open its relevance to human dyslipidemia or context-specific roles.
Background Autosomal dominant familial hypercholesterolemia (ADH; MIM#143890) is one of the most common monogenic disorders characterized by elevated circulatory LDL cholesterol. Initial studies in humans with ADH identified a potential relationship with variants of the gene encoding signal transducing adaptor family member protein 1 (STAP1; MIM#604298). However, subsequent studies have been contradictory. In this study, mice lacking global Stap1 expression (Stap1−/−) were characterized under standard chow and a 42% kcal western diet (WD). Methods Mice were studied for changes in different metabolic parameters before and after a 16-week WD regime. Growth curves, body fats, circulatory lipids, parameters of glucose homeostasis, and liver architecture were studied for comparisons. Results Surprisingly, Stap1−/− mice fed the 16-week WD demonstrated no marked differences in any of the metabolic parameters compared to Stap1+/+ mice. Furthermore, hepatic architecture and cholesterol content in FPLC-isolated lipoprotein fractions also remained comparable to wild-type mice. Conclusion These results strongly suggest that STAP1 does not alter lipid levels, that a western diet did not exacerbate a lipid disorder in Stap1 deficient mice and support the contention that it is not causative for hyperlipidemia in ADH patients. These results support other published studies also questioning the role of this locus in human hypercholesterolemia.
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Kanuri et al. (2020) studied Familial hypercholesterolemia (n=24). Global Stap1 gene knockout vs. Wild-type mice (Stap1+/+) was evaluated on Metabolic parameters including plasma cholesterol, triglycerides, and body composition. Global loss of Stap1 in mice fed a western diet for 16 weeks did not result in an abnormal lipid phenotype or significant changes in metabolic parameters compared to wild-type mice.
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