In a groundbreaking study emerging from Virginia Tech’s College of Agriculture and Life Sciences, researchers have uncovered pivotal insights into how specific types of fats present in infant formulas may precipitate early signs of steatotic liver disease during critical periods of early development. This research, which leverages the neonatal pig model, reveals unexpected metabolic responses in the developing liver, diverging markedly from patterns observed in adult liver disease, and sets a new course for understanding the intricate interactions between early-life nutrition and long-term metabolic health.
Steatotic liver disease, historically classified as non-alcoholic fatty liver disease, is characterized by the accumulation of excessive fat in the liver. While once thought to predominantly affect obese adults, this condition is increasingly diagnosed in pediatric populations, including infants. The evolving epidemiological landscape raises pressing questions about how the nutritional milieu during infancy influences hepatic health trajectories. The Virginia Tech-led study spearheaded by Associate Professor Samer El-Kadi approaches this conundrum by investigating the metabolic impacts of specific fatty acid profiles commonly employed in infant formulas.
Central to the study’s methodology was the use of neonatal pigs, whose digestive physiology and fat metabolism closely mimic those of human infants. This model enabled the team to scrutinize the differential effects of two distinct fat types incorporated into simplified formulas: medium-chain fatty acids predominantly sourced from coconut oil versus long-chain fatty acids derived from animal fats resembling sow milk. Despite delivering identical caloric and protein content, formulas enriched with medium-chain fats induced a more rapid and pronounced hepatic fat deposition compared to those enriched with long-chain fats.
Remarkably, the study disclosed that within just seven days, fatty infiltration of the liver was detectable in pigs fed medium-chain fat formulas. By the two-week mark, this fatty accumulation had escalated into an inflammatory steatotic state, portending more severe liver pathology. This observation is striking given the established understanding from adult studies where steatosis commonly arises from diminished fatty acid oxidation. Contrarily, the developing liver exhibited a concurrent increase in both lipid synthesis and oxidation pathways, demonstrating a unique and paradoxical metabolic milieu.
This phenomenon—simultaneous amplification of anabolic and catabolic lipid pathways—challenges prevailing paradigms and underscores the distinct regulatory mechanisms governing lipid homeostasis during hepatic development. It reveals that, despite the seemingly protective upregulation of fatty acid oxidation, the metabolic adaptations in the immature liver are insufficient to counterbalance the excessive lipogenesis triggered by certain medium-chain fatty acids. The implications of this dysregulation extend beyond basic science, raising the possibility that specific formula compositions might inadvertently predispose infants to early liver disease.
El-Kadi emphasizes that this discovery should be interpreted with caution and not as a critique of infant formula use, which remains an essential and often life-saving nutritional recourse when breastfeeding is not viable. Breast milk continues to be the nutritional gold standard for infants. However, understanding how formula constituents influence metabolic pathways is vital for optimizing formula design and enhancing infant health outcomes globally. This research thus aligns with ongoing efforts by U.S. regulatory bodies such as the Department of Health and Human Services and the Food and Drug Administration, which are actively exploring improvements in infant formula through initiatives like the Operation Stork Speed program.
Future directions of this research encompass detailed investigations into the nuanced roles of different medium-chain fatty acids, their concentrations, and their cumulative impact on hepatic metabolism during early life. El-Kadi’s team aims to elucidate the complex biochemical and physiological underpinnings underlying the concurrent activation of fatty acid synthesis and oxidation, with the ultimate goal of informing nutritional strategies that safeguard against early-onset metabolic disorders.
The study’s lead author, Ravi Yadav, now a postdoctoral researcher at Texas A&M University, along with collaborators such as Marta Lima, Ryan McMillan, and Nishanth Sunny, have contributed their expertise across animal sciences, plant and environmental sciences, human nutrition, and metabolism. Their interdisciplinary approach has been instrumental in dissecting the metabolic idiosyncrasies of the neonatal liver, a critical organ in orchestrating systemic energy balance and metabolic programming.
At the crux of these findings lies a fundamental reassessment of how fat metabolism is regulated during developmental windows previously underappreciated in pediatric research. The emerging evidence signals that early nutrition exerts a profound influence on lifelong liver health, with the potential for modulation through dietary interventions. Such insights propel the scientific community toward designing infant formulas tailored not only to meet macronutrient requirements but also to promote optimal metabolic function at the cellular level.
Recognition of this unique metabolic state in the developing liver also opens avenues for novel biomarkers and therapeutic targets aimed at early detection and prevention of pediatric steatotic liver disease. Clinicians and nutritionists might, in the future, coordinate efforts to refine feeding protocols in neonatal care, integrating metabolic data to customize nutritional plans that minimize hepatic stress while ensuring adequate growth and development.
Underlying this research is the urgent public health imperative to confront the growing incidence of pediatric liver disease, a condition that can predispose affected individuals to serious complications such as steatohepatitis, fibrosis, and even cirrhosis later in life. By advancing fundamental knowledge on the metabolic peculiarities of the neonatal liver and the impact of formula fat composition, Virginia Tech’s study marks a significant step toward mitigating these risks through evidence-based nutritional innovation.
In summary, this comprehensive investigation disrupts established dogma by documenting a concurrent upsurge in fatty acid oxidation and synthesis within the immature liver—a metabolic paradox that facilitates accelerated fat accumulation when exposed to specific medium-chain fats prevalent in some infant formulas. This discovery not only broadens our understanding of pediatric liver disease pathogenesis but also underscores the critical importance of early-life nutrition quality, establishing a foundation for future research aimed at refining infant feeding practices worldwide.
Subject of Research: Effects of specific fats in infant formulas on liver metabolism and early signs of pediatric steatotic liver disease.
Article Title: Concurrent increase in fatty acid oxidation and fatty acid synthesis: a unique metabolic state in a pig model of pediatric steatotic liver disease.
Web References:
https://journals.physiology.org/doi/full/10.1152/ajpendo.00299.2025
References:
Yadav, R., Lima, M., McMillan, R., Sunny, N., & El-Kadi, S. (2024). Concurrent increase in fatty acid oxidation and fatty acid synthesis: a unique metabolic state in a pig model of pediatric steatotic liver disease. American Journal of Physiology-Endocrinology and Metabolism. DOI: 10.1152/ajpendo.00299.2025
Image Credits: Photo by Marya Barlow for Virginia Tech.
Keywords:
Infants, Liver, Nutritional physiology, Nutrients, Nutrition counseling, Organ systems, Organismal biology, Immunology, Diseases and disorders
Tags: early developmental liver metabolismearly onset steatotic liver diseasefatty acid profiles in infant formulainfant formula fat compositioninfant nutrition and liver healthlong-term metabolic health and infant dietmetabolic effects of fatty acids in infantsneonatal fat metabolism researchneonatal pig model for liver researchpediatric liver disease epidemiologypediatric non-alcoholic fatty liver diseaseVirginia Tech liver disease study
