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Peer-reviewedCC BY 4.0Metabolites

Dietary Macronutrient Composition Is Associated with Distinct Hepatic Phenotypes During Post-Weaning Growth: An Integrated Biochemical, Histological, Immunohistochemical and Ultrastructural Study

  • Emrah Zayman1
  • Elif Kayhan1
  • Mehmet Erman Erdemli2
  • Zeynep Erdemli2
  • Feyza İnceoğlu3
  • Mehmet Gül4
4 affiliations
  1. 1Department of Histology and Embryology, Faculty of Medicine, Malatya Turgut Özal University, Malatya 44210, Türkiye
  2. 2Department of Medical Biochemistry, Faculty of Medicine, Inonu University, Malatya 44280, Türkiye
  3. 3Department of Biostatistics and Medical Informatics, Faculty of Medicine, Malatya Turgut Özal University, Malatya 44210, Türkiye
  4. 4Department of Histology and Embryology, Faculty of Medicine, Inonu University, Malatya 44280, Türkiye
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Abstract

Background/Objectives: The aim of this study was to compare the biochemical, histological, immunohistochemical and ultrastructural hepatic phenotypes associated with carbohydrate-, fat- and protein-enriched diets initiated during post-weaning growth. Methods: Forty 21-day-old male Wistar albino rats were divided into four groups: a control group and three experimental groups (carbohydrate, protein, and fat). The respective diets were fed for 13 weeks. Hepatic oxidant–antioxidant parameters, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), histopathological scores; interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) immunoreactivity and transmission electron microscopy (TEM) findings were evaluated. Results: The carbohydrate group showed higher thiobarbituric acid-reactive substances (TBARS), total oxidant status (TOS) and oxidative stress index (OSI), together with lower reduced glutathione (GSH) and total antioxidant status (TAS). Histology showed hydropic change, vacuolization and inflammatory cell infiltration, while TEM showed mitochondrial swelling, loss of cristae and nuclear alterations. The fat group showed prominent vacuolization, TEM-observed lipid droplets, inflammatory cell infiltration and TNF-α immunoreactivity. Most findings in the protein group were closer to control values. Thus, the carbohydrate-enriched diet was associated with the most pronounced redox and ultrastructural injury profile, whereas the fat-enriched diet was associated with a morphological and inflammatory injury profile compatible with lipid accumulation. Conclusions: These findings identify distinct hepatic phenotypes associated with the dietary formulations administered during post-weaning growth. The carbohydrate- and fat-enriched formulations were associated with more pronounced biochemical and morphological changes; inference is made at the level of the complete dietary formulation.

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Cite

BibTeXRIS
BibTeX
@article{zayman2026dietary,
  title = {{Dietary Macronutrient Composition Is Associated with Distinct Hepatic Phenotypes During Post-Weaning Growth: An Integrated Biochemical, Histological, Immunohistochemical and Ultrastructural Study}},
  author = {Emrah Zayman and Elif Kayhan and Mehmet Erman Erdemli and Zeynep Erdemli and Feyza İnceoğlu and Mehmet Gül},
  journal = {Metabolites},
  year = {2026},
  month = oct,
  doi = {10.3390/metabo16100781},
  url = {https://www.mdpi.com/2218-1989/16/10/781},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Dietary Macronutrient Composition Is Associated with Distinct Hepatic Phenotypes During Post-Weaning Growth: An Integrated Biochemical, Histological, Immunohistochemical and Ultrastructural Study
AU  - Emrah Zayman
AU  - Elif Kayhan
AU  - Mehmet Erman Erdemli
AU  - Zeynep Erdemli
AU  - Feyza İnceoğlu
AU  - Mehmet Gül
PY  - 2026
DA  - 2026/10/01
JO  - Metabolites
DO  - 10.3390/metabo16100781
UR  - https://www.mdpi.com/2218-1989/16/10/781
AB  - Background/Objectives: The aim of this study was to compare the biochemical, histological, immunohistochemical and ultrastructural hepatic phenotypes associated with carbohydrate-, fat- and protein-enriched diets initiated during post-weaning growth. Methods: Forty 21-day-old male Wistar albino rats were divided into four groups: a control group and three experimental groups (carbohydrate, protein, and fat). The respective diets were fed for 13 weeks. Hepatic oxidant–antioxidant parameters, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), histopathological scores; interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) immunoreactivity and transmission electron microscopy (TEM) findings were evaluated. Results: The carbohydrate group showed higher thiobarbituric acid-reactive substances (TBARS), total oxidant status (TOS) and oxidative stress index (OSI), together with lower reduced glutathione (GSH) and total antioxidant status (TAS). Histology showed hydropic change, vacuolization and inflammatory cell infiltration, while TEM showed mitochondrial swelling, loss of cristae and nuclear alterations. The fat group showed prominent vacuolization, TEM-observed lipid droplets, inflammatory cell infiltration and TNF-α immunoreactivity. Most findings in the protein group were closer to control values. Thus, the carbohydrate-enriched diet was associated with the most pronounced redox and ultrastructural injury profile, whereas the fat-enriched diet was associated with a morphological and inflammatory injury profile compatible with lipid accumulation. Conclusions: These findings identify distinct hepatic phenotypes associated with the dietary formulations administered during post-weaning growth. The carbohydrate- and fat-enriched formulations were associated with more pronounced biochemical and morphological changes; inference is made at the level of the complete dietary formulation.
SN  - 2218-1989
ER  -