Co-expression Analysis of Sirtuins and Related Metabolic Biomarkers in Juveniles of Gilthead Sea Bream (Sparus aurata) With Differences in Growth Performance

Abstract

Sirtuins (SIRTs) represent a conserved protein family of deacetylases that act as master regulators of metabolism, but little is known about their roles in fish and livestock animals in general. The present study aimed to assess the value of SIRTs for the metabolic phenotyping of fish by assessing their co-expression with a wide-representation of markers of energy and lipid metabolism and intestinal function and health in two genetically different gilthead sea bream strains with differences in growth performance. Fish from the fast-growing strain exhibited higher feed intake, feed efficiency and plasma IGF-I levels, along with higher hepatosomatic index and lower mesenteric fat (lean phenotype). These observations suggest differences in tissue energy partitioning with an increased flux of fatty acids from adipose tissue toward the liver. The resulting increased risk of hepatic steatosis may be counteracted in the liver by reduced lipogenesis and enhanced triglyceride catabolism, in combination with a higher and more efficient oxidative metabolism in white skeletal muscle. These effects were supported by co-regulated changes in the expression profile of SIRTs (liver, sirt1; skeletal muscle, sirt2; adipose tissue, sirt5-6) and markers of oxidative metabolism (pgc1α, cpt1a, cs, nd2, cox1), mitochondrial respiration uncoupling (ucp3) and fatty acid and triglyceride metabolism (pparα, pparγ, elovl5, scd1a, lpl, atgl) that were specific to each strain and tissue. The anterior intestine of the fast-growing strain was better suited to cope with improved growth by increased expression of markers of nutrient absorption (fabp2), epithelial barrier integrity (cdh1, cdh17) and immunity (il1β, cd8b, lgals1, lgals8, sIgT, mIgT), which were correlated with low expression levels of sirt4 and markers of fatty acid oxidation (cpt1a). In the posterior intestine, the fast-growing strain showed a consistent up-regulation of sirt2, sirt3, sirt5 and sirt7 concurrently with increased expression levels of markers of cell proliferation (pcna), oxidative metabolism (nd2) and immunity (sIgT, mIgT). Together, these findings indicate that SIRTs may play different roles in the regulation of metabolism, inflammatory tone and growth in farmed fish, arising as powerful biomarkers for a reliable metabolic phenotyping of fish at the tissue-specific level.

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

“…The scd1a is also highly responsive in gilthead sea bream to changes in nutrient availability [75,76]. More recently, experimental data supported a differential regulation of scd1a in liver and skeletal muscle in a fish strain with a high growth potentiality [11]. In other fish species, it is also well known that lipogenic conditions enhance scd1 expression (carp [35], tilapia [28], pond loach [37]), along with hepatic fat accumulation [28].…”

“…However, high inclusion levels of plant-ingredients are often related with a pro-inflammatory condition with a negative impact on fish health and stress resilience [7][8][9][10]. Plant-based diets can also alter the normal sex proportion ratio, enhancing the male-female reversal in the protandric gilthead sea bream as the result of less powerful functional females during the reproduction period [11]. Several attempts are underway to mitigate these non-desirable effects, and butyrate supplementation of plant-based diets helps to preserve the sex proportion ratio, contributes to prevent the inflammation of the intestinal epithelium, preserving as well the integrity of the intestinal barrier [11,12].…”

“…Plant-based diets can also alter the normal sex proportion ratio, enhancing the male-female reversal in the protandric gilthead sea bream as the result of less powerful functional females during the reproduction period [11]. Several attempts are underway to mitigate these non-desirable effects, and butyrate supplementation of plant-based diets helps to preserve the sex proportion ratio, contributes to prevent the inflammation of the intestinal epithelium, preserving as well the integrity of the intestinal barrier [11,12]. Supplementation with dietary butyrate also has positive effects on the mucus intestinal proteome and the intestinal microbiome, resulting in improved disease outcomes in fish challenged with bacteria or intestinal parasites [13].…”

Somatotropic Axis Regulation Unravels the Differential Effects of Nutritional and Environmental Factors in Growth Performance of Marine Farmed Fishes

“…Relatively less is known about the regulation of sirts in fish, but recent studies in gilthead sea bream highlight that short-term fasting does not alter significantly the sirt1 gene expression in liver, whereas the expression pattern for other sirt isotypes ( sirt2 - 6 ) is an overall suppression linked to reduced energy demand for hepatic lipogenesis ( 102 , 111 ). In contrast, gilthead sea bream strains that regularly perform better than other genetically different strains have a reduced hepatic sirt1 expression, in combination with a more active feeding behavior and Gh/Igf-i system, resulting in enhanced growth and higher circulating Igf-i ( 112 ). The expression of sirt genes is also highly regulated by energy demand in the white skeletal muscle of gilthead sea bream, and sirt2 mRNA is clearly upregulated in fast growing fish, whereas the mitochondrial sirt5 emerges as a more responsive element during forced fasting ( 102 ) or natural fasting when comparisons are made between fishes of different size during the cold season (unpublished results).…”

“… Metabolic crosstalk between Sirtuin-energy sensors and the Gh/Igf system in liver, white skeletal muscle (WSM) and adipose tissue (AT) in two different experimental models: (A) accelerated growth in fishes with enhanced feed and (B) negative energy balance (10-day-fasted fishes). Adapted from Simó-Mirabet et al ( 102 , 112 ). …”