Exhaustive Training Leads to Hepatic Fat Accumulation

Area of Science:

• Exercise Physiology
• Molecular Biology
• Hepatology

Background:

• Overtraining (OT) can impact metabolic pathways, including hepatic lipogenesis.
• The mammalian target of rapamycin complex 1 (mTORC1) pathway is implicated in liver fat accumulation.
• Akt/mTORC1 signaling influences sterol regulatory element binding protein-1 (SREBP-1) activity in lipogenesis.

Purpose of the Study:

• To investigate the effects of different running overtraining (OT) protocols on liver molecular pathways and morphology.
• To compare the impact of downhill, uphill, and level running OT on the mTORC1 signaling pathway and key lipogenic proteins.
• To assess liver cell swelling, inflammation, and fat accumulation under various OT conditions.

Main Methods:

• Mice (C57BL/6) were subjected to three distinct running OT protocols with identical external loads: downhill, uphill, and level.
• Analysis included protein levels of mTORC1 pathway components, SREBP-1, ACC, and FAS.
• Hepatic morphology was examined for signs of cell swelling, inflammation, and fat accumulation.

Main Results:

• Downhill running OT significantly upregulated mTORC1 signaling proteins and SREBP-1 precursor levels.
• Downhill running induced liver cell swelling and acute inflammation.
• All three OT models resulted in hepatic fat accumulation, with uphill and level running causing distinct morphological alterations.

Conclusions:

• Downhill running overtraining exacerbates hepatic lipogenesis via mTORC1 pathway activation and induces inflammatory responses.
• While all tested OT protocols lead to liver fat accumulation, downhill running presents a unique profile of molecular and cellular changes.
• These findings highlight the differential impact of exercise inclination during overtraining on liver health and metabolic regulation.