CYP450 network shifts in MASLD/MASH: from pathogenesis to nutrition-informed modulation
Journal of Nutritional Biochemistry, cilt.158, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Derleme
- Cilt numarası: 158
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.jnutbio.2026.110459
- Dergi Adı: Journal of Nutritional Biochemistry
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, CINAHL, EMBASE, Environment Index, MEDLINE, Academic Search Ultimate (EBSCO)
- Anahtar Kelimeler: CYP4, High-fat diet, MASH, MASLD, Nutrition, Obesity
- Lokman Hekim Üniversitesi Adresli: Evet
Özet
As metabolic dysfunction–associated steatotic liver disease (MASLD)/metabolic dysfunction–associated steatohepatitis (MASH) becomes increasingly prevalent in parallel with obesity, metabolic dysfunction, and ultra-processed dietary patterns, understanding how diet-related exposures influence hepatic drug-metabolizing and lipid-metabolizing pathways has become clinically relevant. Cytochrome P450 (CYP450) enzymes represent a key interface between metabolic stress, xenobiotic handling, oxidative injury, and nutrition-related exposures, yet their role in MASLD/MASH has not been fully integrated from a nutrition-informed perspective. This review maps nutrition–exposure–CYP relationships across MASLD/MASH by integrating dietary patterns, food-processing exposures, contaminants/additives, and bioactive compounds within a structured qualitative framework. The reviewed evidence suggests that obesity, high-fat diet exposure, fructose co-exposure, and fatty acid composition may reshape hepatic CYP responses through isoform-, exposure-, and endpoint-dependent mechanisms. Human liver tissue and microsome studies provide relatively stronger translational evidence for altered CYP3A4 expression, activity, and clearance in NAFLD/NASH, whereas evidence for many nutrition-related exposures remains primarily animal-based, in vitro, or mechanistic. Macronutrient-related pathways, including fructose with high-fat intake and omega-6/omega-3 oxylipin imbalance, appear to influence CYP-mediated lipid and inflammatory signaling. Food-derived contaminants, such as nitrosamines, aflatoxin B1, and acrylamide, provide biologically plausible examples of CYP-dependent bioactivation in metabolically vulnerable liver contexts, although direct human MASLD/MASH validation remains limited. Evidence for food additives and phytochemicals is more preliminary and should be interpreted mainly as hypothesis-generating rather than clinically established. Across the reviewed evidence, metabolic inflammation appears to favor pro-oxidant CYP pathways, including CYP2E1 and CYP4A/4F, while suppressing or altering detoxification and epoxygenase-related pathways, including CYP3A and CYP2C/2J. However, changes in CYP expression do not necessarily translate into altered enzymatic activity or clinical clearance. We conclude that nutrition-related CYP remodeling may represent a mechanistic and translational interface linking diet, oxidative injury, xenobiotic handling, and MASLD/MASH progression. Future studies should integrate dietary exposure assessment with CYP activity or clearance phenotypes, oxidative stress biomarkers, gut–liver axis markers, and MASLD/MASH stage-specific clinical outcomes.