Regulation of FADS2 transcription by SREBP-1 and PPAR-α influences LC-PUFA biosynthesis in fish

Abstract

The present study was conducted to explore the mechanisms leading to differences among fishes in the ability to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFAs). Replacement of fish oil with vegetable oil caused varied degrees of increase in 18-carbon fatty acid content and decrease in n-3 LC-PUFA content in the muscle and liver of rainbow trout (Oncorhynchus mykiss), Japanese seabass (Lateolabrax japonicus) and large yellow croaker (Larimichthys crocea), suggesting that these fishes have differing abilities to biosynthesize LC-PUFAs. Fish oil replacement also led to significantly up-regulated expression of FADS2 and SREBP-1 but different responses of the two PPAR-α homologues in the livers of these three fishes. An in vitro experiment indicated that the basic transcription activity of the FADS2 promoter was significantly higher in rainbow trout than in Japanese seabass or large yellow croaker, which was consistent with their LC-PUFA biosynthetic abilities. In addition, SREBP-1 and PPAR-α up-regulated FADS2 promoter activity. These regulatory effects varied considerably between SREBP-1 and PPAR-α, as well as among the three fishes. Taken together, the differences in regulatory activities of the two transcription factors targeting FADS2 may be responsible for the different LC-PUFA biosynthetic abilities in these three fishes that have adapted to different ambient salinity.

Effect of dietary DHA/EPA ratio on the early development, antioxidant response and lipid metabolism in larvae of Siberia sturgeon (Acipenser baerii, Brandt)

“…Recent studies have shown that HUFAs decrease fat accumulation and affect the activities and gene expression of lipolysis‐related enzymes, such as LPL, which hydrolyses TG of circulating chylomicrons and very low‐density lipoproteins (VLDLs). The transcription factor PPARs play key roles in the catabolism and storage of fatty acids (Kjӕr, Todorčević, Torstensen, Vegusdal, & Ruyter, ; Viswakarma et al, ), in which PPARα is a vital gene that could increase fatty acid oxidation in adipocytes, and its expression levels could reflect the presence of β‐oxidation (Dong et al, ; Zheng et al, ; Zuo, Ai, Mai, & Xu, ). Together with LPL, HL is responsible for the clearance of TG from the circulation (Yang & Subbaiah, ).…”

Stearoyl-CoA desaturase (scd1a) is epigenetically regulated by broodstock nutrition in gilthead sea bream (Sparus aurata)

“…Conversely, a study in mice showed that perinatal manipulation of ALA intake alters Fads2 promoter methylation in offspring livers [64], whereas we showed that the activity of the fish fads2 promoter under our experimental conditions would be more affected by the activity/availability of TFs. Certainly, the regulatory effects of SREBP-1 and PPAR-α in response to dietary fatty acids are quite different in rainbow trout (freshwater), Japanese sea bass (euryhaline) and yellow croaker (marine), which may contribute to the differential LC-PUFA biosynthesis abilities (via fads2 regulation) among fish that have adapted to different ambient salinity [22], and act in concert to other differences such as the presence of a SP1 site in the promoter of freshwater species that is absent in marine fish [23]. Likewise, the nutritional condition of European sea bass larvae with high-or low-PUFA diets did not change the methylation level of 28 CpG sites examined within the fads2 promoter [25].…”

“…The high replacement of marine feed ingredients by alternative raw materials is, thereby, a complex issue, and the total or high replacement of FO by vegetal oils (VO) can compromise fish health [14] and the nutritive value of fish meat [15,16]. This risk assessment is especially relevant in marine farmed fish, since they have a limited ability to convert α-linolenic acid (ALA, 18:3n-3) into eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) [17]. Fatty acid desaturase 2 (Fads2) catalyzes the first and rate limiting step in this pathway and its regulation and activity has been studied in a wide-range of marine (gilthead sea bream [18], black sea bream [19], European sea bass [20], Japanese sea bass [21], large yellow croaker [22], orange-spotted grouper [23]) and freshwater (rainbow trout [22], striped snakehead [24]) fish species.…”

“…This risk assessment is especially relevant in marine farmed fish, since they have a limited ability to convert α-linolenic acid (ALA, 18:3n-3) into eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) [17]. Fatty acid desaturase 2 (Fads2) catalyzes the first and rate limiting step in this pathway and its regulation and activity has been studied in a wide-range of marine (gilthead sea bream [18], black sea bream [19], European sea bass [20], Japanese sea bass [21], large yellow croaker [22], orange-spotted grouper [23]) and freshwater (rainbow trout [22], striped snakehead [24]) fish species. A main outcome is that diets with low levels of n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA) up-regulate the expression of fads2, but with differences among fish species that highly reflect the basal activity of their promoters and their differences in LC-PUFA biosynthetic abilities [22,23,25].…”

“…Fatty acid desaturase 2 (Fads2) catalyzes the first and rate limiting step in this pathway and its regulation and activity has been studied in a wide-range of marine (gilthead sea bream [18], black sea bream [19], European sea bass [20], Japanese sea bass [21], large yellow croaker [22], orange-spotted grouper [23]) and freshwater (rainbow trout [22], striped snakehead [24]) fish species. A main outcome is that diets with low levels of n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA) up-regulate the expression of fads2, but with differences among fish species that highly reflect the basal activity of their promoters and their differences in LC-PUFA biosynthetic abilities [22,23,25]. Conversely, low n-3 C-PUFA diets lead to increased liver fat deposition in freshwater, salmonids and typically marine farmed fish [26][27][28][29], being liver steatosis a common sign of deficiencies in essential fatty acids [30].…”