Eicosapentaenoic acid stimulates leptin receptor gene expression in the hypothalamus of newborn rats
Rita Di Benedetto1, Lucilla Attorri1, Serafina Salvati1
1Food Science, Nutrition and Health Division, Istituto Superiore di Sanità, 00161 Rome, Italy.
Insights
Eicosapentaenoic acid (EPA), a polyunsaturated fatty acid, stimulates early expression of the leptin receptor gene in newborn rats. This finding supports maternal dietary recommendations for fish rich in n-3 PUFAs for infant development.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Body weight and obesity are regulated by leptin (Ob) and its receptor (Ob-Rb).
- In newborn rats, hypothalamic Ob-Rb expression is low despite high Ob levels.
- Polyunsaturated fatty acids (PUFAs) are known gene regulators and are recommended for maternal diets.
Purpose of the Study:
- To investigate the effect of docosahexaenoic acid and eicosapentaenoic acid (EPA) on stimulating Ob-Rb gene expression in newborn rats.
- To determine if PUFAs can influence the early development of leptin receptor signaling.
Main Methods:
- Newborn rats received a single intracerebral ventricle injection of EPA or docosahexaenoic acid on postnatal day 2.
- Hypothalamic tissues were collected on days 1, 2, and 3 post-administration.
- Ob-Rb and Ob messenger RNA levels were analyzed using polymerase chain reaction.
- Ob-Rb protein expression was assessed via Western blot immunoassay.
Main Results:
- EPA administration led to significantly earlier messenger RNA expression of the Ob-Rb gene (24 hours earlier than controls).
- Ob-Rb protein was also detected earlier in rats treated with EPA.
- Docosahexaenoic acid did not show a similar effect on Ob-Rb gene expression.
Conclusions:
- Eicosapentaenoic acid (EPA) plays a role in the early regulation of leptin receptor gene expression in the hypothalamus.
- These findings support the importance of maternal dietary intake of n-3 PUFA-rich foods like fish and seafood.
- Maternal diet composition influences PUFA levels in human milk, potentially impacting infant neurodevelopment and metabolic regulation.
Abstract:
Body weight and obesity are controlled by the binding leptin (Ob) receptor, but in newborn rats, despite high Ob levels, hypothalamic leptin receptors (Ob-Rb) are only weakly expressed. In this study we have attempted to stimulate expression of the Ob-Rb gene by administering 2 polyunsaturated fatty acids (PUFAs) recommended for the maternal diet and known as gene regulators: docosahexaenoic acid and eicosapentaenoic acid (EPA). We studied the effects of a single dose injected into a cerebral ventricle of newborn rats on postnatal day 2. On days 1, 2, and 3 after administration, we dissected the hypothalamus and analyzed Ob-Rb and Ob messenger RNAs by polymerase chain reaction and protein expression by Western blot immunoassay. Our results demonstrate that EPA, but not docosahexaenoic acid, caused an early messenger RNA expression of the gene, 24 hours earlier than in the controls, and the protein was also detected earlier. Our data corroborate the observations regarding the role of PUFAs, EPA in particular, in the regulation of gene expression. In addition, they support the recommendation to enrich the maternal diet with fish and seafood rich in n-3 PUFA, because the concentrations of n-6 and n-3 PUFA in human milk reflect the composition of fat in the mother's diet.
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