Interaction Between Photoperiod and Sex on Hepatic Lipid Homeostasis in Rats Fed an Obesogenic Diet

Abstract

Seasonal changes in day length as well as sex are critical factors influencing metabolic processes. However, their combined impact on liver lipid metabolism under obesogenic conditions remains unclear. This study aims to investigate the interaction between sex and photoperiod on liver lipid homeostasis in obese Fischer 344 (F344) rats, with a special emphasis on the underlying molecular mechanisms. To this aim, male and female rats were fed with a cafeteria diet (CAF) for 11 weeks and exposed to either long (L18, 18 h of light/day) or short (L6, 6 h of light/day) photoperiods for the last 8 weeks. Liver histological analysis, hepatic damage markers, plasmatic and hepatic lipid profiles as well as hepatic gene expression related to lipid metabolism were performed. Results indicate that males exposed to the L18 photoperiod developed hepatic macro-steatosis and exacerbated hepatic lipid accumulation, leading to increased liver weight and total hepatic lipids compared to their L6 photoperiod counterparts. At the molecular level, males under the L18 photoperiod, showed downregulation of the lipid transporter Fabp4 and upregulation of β-oxidation related genes. On the other hand, female rats exhibited a healthier lipid profile compared to males when exposed to both L6 and L18 photoperiods, and a lower degree of steatosis. Gene analysis revealed that the lipid transporter Mtp expression was significantly higher in females under the L18 photoperiod. In conclusion, photoperiod and sex influence hepatic lipid metabolism in rats fed an obesogenic diet, highlighting the importance of considering these factors in understanding and addressing metabolic disorders and reinforcing the concept of precision medicine.