Intravenous leiomyomatosis: A retrospective case series of imaging findings and diagnostic challenges.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health crisis driven largely by modern dietary habits [,,]. A critical limitation in preclinical research is the near-universal reliance on continuous high-fat feeding paradigms, which, although effective in inducing steatosis, fail to recapitulate the cyclical, intermittent nature of human Western diet consumption. This is particularly relevant given that populations with cyclical dietary exposure can develop MASLD even in the absence of overt caloric excess, suggesting that dietary periodicity is an independent contributor to disease risk. The physiological consequence of this mismatch is underscored by cardiovascular research demonstrating that intermittent, but not continuous, hyperlipidemia accelerates atherosclerosis through lasting reprogramming of resident macrophages and neutrophils [,]. Together, these observations establish dietary periodicity as an independent pathological factor and underscore the urgent need to adopt dynamic feeding models in MASLD research. To date, however, a systematic comparison of continuous versus intermittent high-fat, high-cholesterol (HFHC) dietary regimens in a translationally relevant MASLD model is entirely lacking. The guinea pig () is uniquely positioned to bridge this gap because it circumvents the fundamental limitations of murine models in recapitulating human lipid metabolism and MASLD pathogenesis. A pivotal species divergence lies in hepatic apolipoprotein B (ApoB) mRNA editing. The mouse liver highly expresses the editing enzyme, which converts ApoB-100 to the truncated ApoB-48. Consequently, mice secrete ApoB-48-containing VLDL particles that are rapidly cleared and cannot be converted to LDL, yielding an HDL-dominant profile and marked resistance to dietary cholesterol-induced hypercholesterolemia []. In stark contrast, the guinea pig—like the human—exhibits negligible hepatic ApoB mRNA editing, produces ApoB-100-containing VLDL, and maintains an LDL-dominant lipoprotein profile that is exquisitely sensitive to dietary fat and cholesterol [,,,,,]. This fundamental similarity extends to hepatic cholesterol handling: upon dietary cholesterol challenge, wild-type mice partition excess cholesterol into bile acids for excretion, whereas guinea pigs and humans accumulate hepatic cholesteryl ester, a hallmark of human MASLD that directly contributes to lipotoxicity, inflammasome activation, and stellate cell-driven fibrogenesis. Because of these metabolic defenses, mice typically require genetic modifications (e.g., Ldlr or Apoe) or choline-deficient diets to develop robust steatohepatitis with fibrosis: interventions that distort the very metabolic pathways they aim to model []. In contrast, the guinea pig fed a high-fat, high-cholesterol diet spontaneously progresses from steatosis to steatohepatitis with ballooning degeneration and bridging fibrosis, faithfully recapitulating the histological spectrum of human disease without genetic or severe nutritional manipulation []. Beyond hepatic lipid metabolism, the guinea pig offers a critical advantage in modeling the gut–liver axis. As a strict herbivore adapted to a high-fiber diet, it possesses a voluminous, fermentation-competent cecum that generates short-chain fatty acids and other microbiota-derived metabolites in a pattern that closely mirrors human colonic fermentation, a feature that the murine cecum—given the mouse’s omnivorous physiology—replicates less faithfully [,,]. This unique confluence of human-like lipoprotein handling, dietary-driven steatohepatitis, and hindgut fermentation establishes the guinea pig as a superior translational platform for investigating how diet composition and pattern intersect to drive MASLD. To address the identified gap, we performed an integrated multi-omics analysis combining serum metabolomics, fecal 16S rRNA sequencing, and liver transcriptomics in guinea pigs subjected to continuous versus intermittent HFHC feeding. We further tested a targeted nutritional intervention—dietary flaxseed lignan supplementation—to determine whether restoration of the gut microbiota–enterolactone axis can counteract the liver injury specifically driven by the intermittent regimen.