ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition and Metabolism
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1665682
This article is part of the Research TopicNutritional Pathways in Metabolic and Reproductive HealthView all articles
Long-term dietary restriction changes lipid homeostasis and consequently impairs testosterone production in aged Wistar rats
Provisionally accepted
- Siniša Stanković Institute for Biological Research, University of Belgrade, Belgrade, Serbia
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Testosterone (T) is a central androgen responsible for the maintenance of vegetative and reproductive functions and sexual behavior in males. T is mainly synthesized through the process of testicular steroidogenesis with cholesterol (CHOL) as the initial precursor. It is known that T levels gradually decrease, along with an increase in CHOL, LDL-C, triglycerides (TG), and a decrease in HDL-C in advanced stages of life. Dietary restriction (DR) ameliorates lipid status and raises T levels in obese and overweight men. Here, we investigated whether the beneficial effects of DR on serum lipid status consequently improve T production at advanced stages; therefore, we exposed male Wistar rats to long-term DR (LTDR, 18 months). We confirmed an age-related decrease in serum T levels, reduced expression of genes and proteins of steroidogenic machinery with a simultaneous increase in serum CHOL, LDL-C, and TG levels. LTDR additionally decreased T synthesis, expression of Star/StAR and Cyp11a1/CYP11A1, and testicular CHOL levels. At the same time, LTDR reduced serum CHOL, LDL-C, and TG levels and increased HDL-C levels. To confirm that the effects of DR are determined by the duration of the treatment, we also checked the effects of the short-term DR (STDR, 3 months) and demonstrated that STDR did not alter T levels and did not affect serum lipids. Our results indicate the importance of sustained systemic lipid homeostasis for T production in advanced life stages and show that the effects of restricted food intake on testicular androgen capacity depend on the duration of DR.
Keywords: Testosterone, Cholesterol, LDL-C, HDL-C, Long-term dietary restriction, short-termdietary restriction
Received: 14 Jul 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Sokanovic, Prvulovic, Simeunovic, Praćer and Mladenovic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Srdjan Sokanovic, Siniša Stanković Institute for Biological Research, University of Belgrade, Belgrade, Serbia
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