The core premise of nutrigenomics is deceptively simple. Nutrients do not merely fuel a fish; they act as chemical signals that switch genes on and off, reshaping metabolism, immunity, and growth at the molecular level. The field emerged in the late 1990s at the intersection of nutritional science and genomics, and it has since migrated from human medicine into livestock and, more recently, into aquaculture. Farmed fish are an especially attractive target because their diets are entirely controlled by producers. If researchers can identify which genes respond to which dietary ingredients, they can in principle design feeds that maximize feed conversion efficiency, strengthen disease resistance, and even alter the nutritional profile of the fillet that reaches the consumer’s plate. The retracted review argued that this approach could transform aquaculture into a precision discipline, where rations are tailored to the genome of each species rather than formulated by trial and error.

The technological engine behind this vision is a battery of omics tools. Whole genome sequencing has supplied reference assemblies for major farmed species, while RNA sequencing, or transcriptomics, allows scientists to measure which genes are active in fish fed different diets, exposing the molecular fingerprints of each ration. Proteomics extends the analysis to the proteins those genes produce, and metabolomics captures the biochemical end products of metabolism, closing the loop between gene and physiology. Perhaps the most disruptive entry is CRISPR gene editing, which enables researchers to deliberately disable or modify genes suspected of governing feed efficiency, fatty acid synthesis, or stress tolerance, then observe the consequences. The review highlighted these tools as the foundation for identifying the genetic pathways that control how fish digest proteins, metabolize lipids, and mount immune responses, turning what was once an opaque black box into an experimentally tractable system.

Among the nutritional pathways receiving the most attention, lipid metabolism stands out. Lipids are a principal energy source for many fish, and the genes governing fatty acid synthesis, elongation, and desaturation determine whether a farmed fish can build health-promoting omega-3 fatty acids such as EPA and DHA from plant-based feed ingredients. The review cited work on hybrid grouper showing that high-lipid diets cause hepatic fat accumulation and that bile acids modulate this process. Carbohydrate metabolism presents a parallel puzzle: carnivorous fish express low levels of amylase and glucokinase and therefore handle starch poorly. A single-nuclei RNA sequencing study of largemouth bass fed high-carbohydrate diets revealed disturbed hepatic energy metabolism and activation of oxidative stress and liver fibrosis pathways, while whole genome resequencing combined with RNA sequencing linked genes such as fabp6, lpcat2, pla2g1b, and pentose phosphate pathway genes to growth performance under carbohydrate-rich, thermally fluctuating conditions.

Species-specific findings form the empirical backbone of the field. In Atlantic salmon, research has concentrated on lipid metabolism and immune function, including the identification of genes involved in omega-3 biosynthesis and pathogen resistance. One frequently cited study replaced fish oil with vegetable oil in salmon diets and used liver transcriptomics to track the consequences: genes for fatty acid biosynthesis, inflammation, and oxidative stress, including fasn, cox2, and pparα, shifted expression, signaling a fundamental rewiring of lipid handling. Tilapia has served as a model for testing plant-based alternative feeds on nutrient utilization and growth, while catfish studies have uncovered nutrigenomic pathways tied to hypoxia tolerance and feed efficiency, informing breeding programs for hardier strains. Carp, with their natural talent for carbohydrate metabolism, are being studied as candidates for sustainable plant-based feeding, a trait that could ease pressure on wild-capture fisheries that supply fishmeal.

The larval stage of farmed fish has emerged as a particularly sensitive window where nutrition leaves lasting genomic marks. Larvae are typically reared on live feeds such as rotifers and artemia, enriched with phospholipids, fatty acids, and micronutrients that support growth, survival, and disease resistance. Researchers formulating a microdiet of 22 percent lipid and 52 percent protein for pike silverside larvae found differential gene expression and overexpression of apoptotic, DNA damage repair, and oxidative stress genes, which correlated with suboptimal growth and survival, prompting a recommendation to reduce lipid content. De novo transcriptomic sequencing of tropical gar embryos and larvae identified nutrigenomic markers spanning cell cycle, digestion, muscle development, and behavioral genes. In Atlantic cod larvae, RNA sequencing and qPCR revealed that fast-moving copepod prey stimulated swimming activity, boosting glycolysis and oxidative phosphorylation in muscle cells but also elevating reactive oxygen species, a burden that prey nutritional quality must counterbalance. Adding alpha lipoic acid to pike silverside microdiets improved larval survival and feed efficiency by modulating mitochondrial biogenesis and DNA repair.

Beyond growth, nutrigenomics is being deployed to armor fish against disease through diet rather than drugs. Functional feeds enriched with probiotics, prebiotics, or plant-derived bioactive compounds have been shown to reshape the expression of immune-related genes. In rainbow trout, dietary supplementation with the probiotic Lactobacillus rhamnosus upregulated genes governing gut barrier function, including mucins and tight junction proteins, alongside immune genes such as cytokines and toll-like receptors. In Pacific white shrimp, vitamin C supplementation upregulated antioxidant defenses, including sod and cat, and immune genes including toll-like receptors and penaeidins, increasing resistance to the pathogenic bacterium Vibrio parahaemolyticus. Selenium studies in rainbow trout demonstrated that organic selenomethionine significantly upregulated antioxidant genes such as gpx1 and sod2, reducing markers of oxidative stress, while laminarin, a bioactive polysaccharide from brown algae, altered immune gene expression in abalone. Microalgal diets rich in Isochrysis galbana upregulated energy metabolism genes in Pacific oysters, and vitamin C-enriched diets in tilapia boosted SOD and CAT expression while dialing down the stress marker HSP70.

The human-health dimension of this research extends to biofortification and contaminant control. Because omega-3 fatty acids reduce cardiovascular risk and support cognitive function, researchers are pursuing fish strains genetically optimized for EPA and DHA production, including transgenic strategies that stimulate desaturase gene expression. Nutrigenomic approaches may also identify genes governing the metabolism and detoxification of heavy metals and pesticides, opening a route to fish lines that accumulate fewer contaminants and meet stricter food safety standards. The review even sketched a vision of regionally tailored products, fish engineered or selectively bred to carry more selenium or vitamin A precursors, addressing specific nutrient deficiencies in particular populations. By contrast, plant protein substitution is not without molecular cost: in zebrafish fed soybean meal, transcriptomics revealed altered lipid homeostasis through genes such as ppara, fabp2, mttp, and cyp7a1, along with mild intestinal inflammation marked by elevated pro-inflammatory cytokines.

The retraction of this particular review does not settle any of these scientific questions, but it does underscore the scrutiny that fast-moving fields attract, and it coincides with a candid discussion of the field’s unresolved problems. The review itself acknowledged that RNA sequencing and CRISPR remain expensive, that bioinformatics capacity is a bottleneck for many aquaculture facilities, and that genetically modified fish raise public acceptance concerns, biodiversity risks, and ecological hazards if transgenic animals escape and interbreed with wild populations. Looking forward, it pointed to artificial intelligence and machine learning for predicting gene-nutrient interactions and optimizing feed formulas, multi-omics integration for holistic views of fish biology, and cross-sector partnerships to build affordable technologies and responsible regulatory frameworks. Readers should consult the publisher’s retraction notice before relying on any claim from the withdrawn article, but the underlying research program it surveyed, from copepod-fed cod larvae to CRISPR-edited salmon, continues to advance in the peer-reviewed literature, carrying the promise of seafood that is healthier for people and gentler on the planet.

Subject of Research: Fish nutrigenomics and its application to sustainable aquaculture nutrition

Article Title: RETRACTED ARTICLE: Fish nutrigenomics: unravelling the genetic code for sustainable aquaculture and improved nutritional benefits

Article References: Iqbal, G., Wani, M. N., Piyushbhai, M. K., Dar, S. A., & Sharma, A. (2025). RETRACTED ARTICLE: Fish nutrigenomics: unravelling the genetic code for sustainable aquaculture and improved nutritional benefits. Blue Biotechnology, 2(1), Article 19. https://doi.org/10.1186/s44315-025-00043-9

Image Credits: AI Generated

DOI: 10.1186/s44315-025-00043-9

Keywords: nutrigenomics, aquaculture, fish nutrition, genomics, CRISPR, RNA sequencing, omega-3 fatty acids, feed efficiency, disease resistance, transcriptomics, sustainable food, retraction

The research, led by Camila S. da Silva of Embrapa Mid-North together with colleagues at Embrapa Dairy Cattle in Minas Gerais, Michigan State University, and the Federal University of Minas Gerais, was conducted at the Multi-User Laboratory of Livestock Bioefficiency and Sustainability in Coronel Pacheco, a humid subtropical site in the heart of Brazilian dairy country. The heifers entered the trial at roughly two and a half years of age with an average body weight of 563 kilograms. None were inseminated during the study, a deliberate design choice that removed pregnancy as a confounding factor and allowed the researchers to isolate how lactation itself reshapes the animal’s energy economy. The cows were housed in a free-stall barn equipped with electronic feed bins and automated weighing platforms, so that every kilogram of feed consumed and every fluctuation in body weight was captured in real time.

The animals received a total mixed ration based on corn silage, chopped hay, soybean meal, ground corn, urea, and minerals, reformulated at each of three lactation stages so that the roughage-to-concentrate ratio shifted from 62:38 in early lactation to 81:19 by late lactation. The diet supplied on average 18.41 megajoules of gross energy per kilogram of dry matter. Measuring what happened to that energy required an unusually demanding experimental battery: six total-tract digestibility trials, in which feces were collected completely over five consecutive days and urine was sampled by spot collections; and respirometry sessions in open-circuit respiration chambers, where cows spent 22-hour periods under thermoneutral conditions while oxygen consumption, carbon dioxide production, and methane output were quantified. From these measurements the team calculated digestible energy intake, metabolizable energy intake, heat production, and ultimately the full energy balance of each cow.

The headline finding is that these animals are, metabolically speaking, unusually comfortable dairy cows. Milk yield averaged 16.1 kilograms per day, with fat-corrected yield at 18.4 kilograms, moderate figures by Holstein standards but achieved with striking stability. Dry matter intake held nearly flat across the lactation, drifting only from 15.7 kilograms per day in early lactation to 14.7 in late lactation. Digestible and metabolizable energy intakes likewise barely moved, hovering near 180 and 150 megajoules per day respectively. In contrast to the dramatic metabolic rollercoaster familiar from high-producing Holsteins, the F1 crossbreds simply never fell into a deep or prolonged energy deficit. Their energy balance dipped to only about −12.9 megajoules per day in the earliest stage and turned positive, reaching +8.8 megajoules per day, once cows reached mid-lactation.

That short negative phase is arguably the study’s most consequential result. In purebred Holsteins selected for extreme yields, the weeks after calving typically bring a punishing gap between the energy poured into milk and the energy the cow can physically consume, forcing the animal to mobilize body reserves and predisposing her to ketosis, impaired fertility, and other transition disorders. The F1 cows in this study resolved their negative balance within roughly two to three weeks postpartum. The authors attribute this resilience to the combination of moderate milk output, stable intake, and a genetic predisposition toward fat storage inherited partly from the zebu side. Bos indicus cattle and their crosses deposit proportionally more subcutaneous fat, whereas Holsteins accumulate visceral fat and channel nutrients preferentially into the mammary gland, leaving pure Holsteins metabolically far more vulnerable in early lactation.

Body condition data reinforced this picture. The cows averaged a body condition score of 3.7 on the five-point scale just two weeks after calving, climbed to 4.2 by fifteen weeks, and settled at 4.4 by week twenty-eight—a whole-lactation average of 4.1. Body weight rose steadily from around 592 kilograms in early lactation to 695 kilograms in late lactation, with the animals reaching about 726 kilograms at forty-two weeks in milk. Because the heifers had calved at roughly 78 percent of their hypothetical mature weight at thirty months, the researchers conclude that these animals grew faster than the average Brazilian Girolando herd, likely reflecting the standardized genetics and intensive rearing nutrition applied from calfhood onward. Still growing while lactating, they were effectively funding two demanding biological projects simultaneously without apparent metabolic strain.

The partitioning of dietary energy reveals where the calories went. Heat production was the single largest expenditure, consuming 34.1 percent of gross energy intake, with cows losing between 96.1 and 89.0 megajoules per day as heat across the three stages. Fecal energy losses came a close second at 33.2 percent, a figure that reflects the substantial roughage content of the rations, while urinary losses remained a minor and remarkably constant 3.4 megajoules per day. Energy retained in milk accounted for 20 percent of gross intake, declining from 61.2 megajoules per day in early lactation to 46.0 in late lactation as milk yield fell. Notably, and counter to what has been reported for Holsteins, both heat and methane losses declined rather than rose from early to late lactation in these crossbreds, most likely because energy intake itself tapered alongside the falling concentrate proportion of the diet.

The methane numbers carry implications well beyond cattle nutrition. Enteric methane represented 7.6 percent of gross energy intake—a methane conversion factor about one percentage point above the 6.5 percent default that the Intergovernmental Panel on Climate Change assigns to cattle and buffalo. In absolute terms, methane energy losses fell from 22.8 megajoules per day in early lactation to 18.6 in late lactation. The authors urge caution in generalizing the figure, since fiber fractions and feeding level strongly influence rumen passage rate and thus methanogenesis, and their diets contained only about half the concentrate of some comparison studies. Indeed, crossbred cows in comparable trials lost more energy as methane than Holsteins or Jerseys on high-concentrate rations. Still, with livestock methane under intensifying scrutiny as a greenhouse gas, the data identify a concrete research target: understanding and mitigating methane conversion in F1 and other Girolando compositions under tropical feeding systems.

Milk composition adds another dimension to the crossbred’s commercial case. The cows produced milk with an average fat content of 4.66 percent and protein of 3.57 percent, sitting at the upper end of published ranges for Girolando animals and above the breed averages of roughly 3.9 and 3.3 percent. Since pure Holsteins typically produce a larger but skimmer volume, the solids-rich F1 milk can counterbalance the yield gap, particularly attractive for producers diversifying into cheese and other dairy products. Feed efficiency told a similar intermediate story: cows converted each kilogram of dry matter into 1.16 kilograms of milk in early lactation, declining to 0.93 by late lactation, with an overall lactation figure near 1.05—better than Gyr, below elite Holstein, and potentially convergent with both when nutrient availability is not limiting.

Taken together, the study delivers a persuasive argument that F1 Holstein × Gyr cows are a viable and physiologically sustainable option for confined tropical milk production, combining heat tolerance and intake stability with acceptable yields and unusually gentle metabolic transitions. The authors are careful to note the caveats: the favorable energy balance reflects not only genotype but also excellent nutrition and a comparatively late age at first calving, and the pronounced tendency toward over-conditioning in mid-to-late lactation demands careful dietary energy control before subsequent calvings. They also emphasize that comparable measurements under grazing conditions—where most tropical F1 cows actually live—are essential next steps. But as a metabolic portrait of the cow that milks Brazil, the data finally fill in the energy ledger, showing precisely how a hybrid animal manages to give milk, gain weight, stay cool, and recover from calving faster than either of its parent breeds could alone.

Subject of Research: Energy metabolism and partitioning in primiparous F1 Holstein × Gyr dairy cows throughout lactation

Article Title: Unveiling the energy metabolism of primiparous F1 Holstein × Gyr cows throughout lactation

Article References: da Silva, C. S., Rodrigues, J. P. P., Sacramento, J. P., Coelho, S. G., & Campos, M. M. (2026). Unveiling the energy metabolism of primiparous F1 Holstein × Gyr cows throughout lactation. Discover Agriculture, 4(1), Article 296. https://doi.org/10.1007/s44279-026-00774-2

Image Credits: AI Generated

DOI: 10.1007/s44279-026-00774-2

Keywords: dairy cattle, Holstein, Gyr, Girolando, energy metabolism, lactation, tropical agriculture, methane emissions, body condition, feed efficiency, crossbreeding, respirometry