Abstract
The beneficial effects of fatty acids (FAs) on human health have attracted widespread interest. However, little is known about the impact of FAs on the handling of urate, the end-product of human purine metabolism, in the body. Increased serum urate levels occur in hyperuricemia, a disease that can lead to gout. In humans, urate filtered by the glomerulus of the kidney is majorly re-absorbed from primary urine into the blood via the urate transporter 1 (URAT1)-mediated pathway. URAT1 inhibition, thus, contributes to decreasing serum urate concentration by increasing net renal urate excretion. Here, we investigated the URAT1-inhibitory effects of 25 FAs that are commonly contained in foods or produced in the body. For this purpose, we conducted an in vitro transport assay using cells transiently expressing URAT1. Our results showed that unsaturated FAs, especially long-chain unsaturated FAs, inhibited URAT1 more strongly than saturated FAs. Among the tested unsaturated FAs, eicosapentaenoic acid, α-linolenic acid, and docosahexaenoic acid exhibited substantial URAT1-inhibitory activities, with half maximal inhibitory concentration values of 6.0, 14.2, and 15.2 μM, respectively. Although further studies are required to investigate whether the ω-3 polyunsaturated FAs can be employed as uricosuric agents, our findings further confirm FAs as nutritionally important substances influencing human health.
Highlights
Fatty acids (FAs) are physiologically important as energy sources and membrane constituents; fatty acids (FAs) have diverse biological activities that modulate numerous cell/tissue properties in living organisms [1]
We examined the urate transporter 1 (URAT1)-inhibitory effects of 25 FAs using an in vitro transport assay with mammalian cells transiently expressing URAT1
Prior to screening the inhibitory effects of 25 FAs on URAT1, we verified our cell-based assay system—an in vitro urate transport assay with mammalian cells transiently expressing URAT1 (Figure 1)
Summary
Fatty acids (FAs) are physiologically important as energy sources and membrane constituents; FAs have diverse biological activities that modulate numerous cell/tissue properties in living organisms [1]. Accumulating evidence suggests that via such actions, dietary FAs can influence human health, well-being, and the risk of disease development. Intake of polyunsaturated fatty acids (PUFAs) of the ω-3 family, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been considered to reduce the risk of chronic diseases including cardiovascular diseases; other effects of FAs consumption on human health remain controversial and need further investigation [2,3,4,5]. Little is known about the association between FAs and hyperuricemia, a common urate-related disease, especially regarding the effects of FAs on urate-handling machineries in the body. As hyperuricemia is a risk factor for gout, a very common form of inflammatory arthritis, SUA management at appropriate levels is becoming increasingly important in daily life [7,8]. Only 3%–10% of the urate filtered by the glomerulus of the kidney is secreted to the urine [11] because most of it is re-absorbed from the primary urine into the blood in the proximal tubule by the urate transporter 1 (URAT1, known as SLC22A12)-mediated pathway [12]
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