When obesity develops without the metabolic damage that usually accompanies it, the body’s tissues appear to respond in strikingly different ways. A new study in BMC Genomics reports that Ossabaw pigs fed an obesity-inducing diet for 11 weeks gained substantial weight and body size while remaining metabolically healthy, and that their visceral adipose tissue and liver mounted sharply contrasting transcriptional responses to the same dietary challenge.
The research team, led by Catarina Ventura and Peter M. H. Heegaard with colleagues including Buwen Liang, Katharina B. Kuentzel, Jan Gorodkin and Trisha J. Grevengoed, fed obesity-prone Ossabaw pigs a medium-cholesterol, high-fat and high-fructose diet containing 0.5 percent cholesterol by weight, 50 percent of energy from fat and 21 percent of energy from fructose. After 11 weeks on this diet, the animals showed significant increases in body weight, body size and adipocyte area compared with control pigs. Crucially, they remained metabolically healthy: C-reactive protein, triglyceride, glucose and insulin levels were normal, and low-density lipoprotein rose only slightly and not significantly.
To characterize how the tissues responded at the molecular level, the researchers performed RNA sequencing on visceral adipose tissue and liver. In visceral adipose tissue they identified 666 differentially expressed transcripts, whereas only 40 were found in liver. FASN, a gene involved in fatty acid synthesis, was the only transcript regulated in the same direction in both tissues, and it was significantly downregulated in each, pointing to largely tissue-specific transcriptional signatures.
The pattern within each tissue was distinctive. In visceral adipose tissue, transcripts related to oxidative phosphorylation and protein synthesis were upregulated, while transcripts connected to inflammation and signaling receptor complexes were generally downregulated. The authors describe this as an ‘obesity tolerant’ response, in which the fat tissue appeared to absorb the dietary challenge without activating inflammatory programs.
The liver told a different story. Compared with visceral adipose tissue, the liver of the diet-fed pigs showed greater enrichment of transcripts commonly linked to obesity. Transcripts associated with acyl-CoA metabolic processes and protein synthesis were suppressed, while transcripts related to extracellular matrix, signaling receptor activity and regulation of inflammation were upregulated. According to the authors, this liver profile resembles an early canonical obesity response, in contrast to the tolerant pattern seen in fat tissue.
Taken together, the authors conclude that the diet-fed Ossabaw pigs attained a pre-metabolic syndrome state of obesity, meaning obesity without other risk factors of the metabolic syndrome. This pig model, they suggest, offers a window into the earliest stages of obesity pathophysiology, spanning the range from preclinical obesity, defined as excess body fat without overt disease, to clinical obesity with impairment of organ function.
The study is limited by its relatively short feeding period of 11 weeks and by its use of an animal model, so the findings describe early transcriptional changes in pigs rather than long-term outcomes in humans. Nevertheless, the divergence between a tolerant adipose tissue response and an early obesity-like liver response suggests that the two organs may follow different trajectories as obesity progresses, a distinction that could inform future work on when and why metabolic disease begins to emerge.
Subject of Research: Transcriptional changes in adipose tissue and liver during early diet-induced obesity in Ossabaw pigs
Article Title: Pre-metabolic syndrome transcriptional response of adipose tissue and liver to obesity in the Ossabaw pig model
Article References: Ventura, C., Liang, B., Kuentzel, K. B., Gorodkin, J., Grevengoed, T. J., & Heegaard, P. M. H. (2026). Pre-metabolic syndrome transcriptional response of adipose tissue and liver to obesity in the Ossabaw pig model. BMC Genomics. https://doi.org/10.1186/s12864-026-13389-0
Image Credits: AI Generated
DOI: 10.1186/s12864-026-13389-0
Keywords: obesity, Ossabaw pig, transcriptomics, RNA sequencing, visceral adipose tissue, liver, metabolic syndrome, high-fat diet, fructose, gene expression, pre-metabolic syndrome, Pre-metabolic
News Source: Juliet Wilcox. (October 28, 2026). Obese pigs stay metabolically healthy as fat and liver tissue diverge in gene response. Scienmag.
