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Isolation and Primary Culture of Rat Hepatic Cells
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In Utero Protein Deficiency Leads to Impaired Hepatic Lipid Metabolism in Adult Male Rats
Vipin A Vidyadharan1, Chandrasekhar Yallampalli1, Chellakkan S Blesson2
1Basic Sciences Perinatology Research Laboratories, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, United States.
The Journal of Nutrition
|February 13, 2026
Summary
Maternal low-protein diet exposure during gestation programs male rat offspring for hepatic lipid accumulation and impaired mitochondrial function, increasing lean Type 2 Diabetes risk.
Area of Science:
- Metabolic Research
- Developmental Biology
- Mitochondrial Biology
Background:
- In-utero exposure to a low-protein (LP) diet is a key model for developmental programming.
- This programming is linked to an increased risk of chronic metabolic diseases, including lean Type 2 Diabetes (T2D).
Purpose of the Study:
- To investigate the long-term effects of maternal LP diet on hepatic lipid metabolism.
- To examine mitochondrial dynamics in adult male rat offspring with lean T2D.
Main Methods:
- Pregnant Wistar rats received either a control or LP diet during gestation.
- Hepatic lipid accumulation, mitochondrial function, and signaling pathways were analyzed in adult male offspring.
- Histological, metabolomic, and molecular methods were employed, with statistical analysis using Student's t-test and two-way ANOVA.
Main Results:
- LP-programmed livers showed a 55% increase in lipid droplet area and elevated carnitine levels, indicating disrupted fatty-acid handling.
- Downregulation of beta-oxidation genes and upregulation of lipogenic genes suggest a shift toward lipid synthesis.
- Impaired oxidative metabolism was observed, with reduced TCA-cycle intermediates and altered mitochondrial dynamics, including compromised mitophagy.
Conclusions:
- In-utero protein restriction leads to persistent hepatic mitochondrial dysfunction and altered lipid metabolism.
- These changes contribute to the developmental origins of insulin resistance and metabolic dysfunction.
- The study highlights the long-lasting impact of early-life nutrition on metabolic health.
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