# Persistence of the hepatic benefits of high-intensity interval training (HIIT) during detraining despite body weight regain in mice

## TL;DR

High-intensity interval training (HIIT) improves liver health in mice, and these benefits last even after training stops and weight is regained.

## Contribution

The study shows that hepatic benefits of HIIT persist during detraining despite body weight regain in mice.

## Key findings

- HIIT reduced body mass and improved glucose tolerance in mice on a high-fat diet.
- Hepatic steatosis was significantly alleviated in all training groups, even after detraining.
- HIIT downregulated lipogenic genes and upregulated β-oxidation genes, with reduced ER stress markers sustained during detraining.

## Abstract

High-intensity interval training (HIIT) is an effective intervention for improving metabolic health and mitigating metabolic dysfunction-associated steatotic liver disease (MASLD). Nonetheless, the stability of these benefits throughout detraining periods and upon weight regain remains inadequately characterized. This study aimed to evaluate whether hepatic improvements induced by HIIT are sustained during detraining, even after body weight regain. Eighty male C57BL/6 mice were fed either a control (10% fat) or a high-fat (HF) diet (50% fat) for 12 weeks. Following this period, the animals were allocated to groups subjected to continuous HIIT or intermittent training cycles (each lasting 3 weeks). The outcomes assessed included body mass (BM), glucose tolerance, lipid profiles, liver enzyme levels (aspartate aminotransferase and alanine aminotransferase), hepatic steatosis, and the expression profiles of genes associated with lipogenesis (Srebf1, Mlxpl, and Fas), β-oxidation (Ppara and Cpt1a), and endoplasmic reticulum (ER) stress (Atf4, Ddit3, and Gadd45). Compared with the sedentary HF-NT condition, continuous HIIT reduced BM and improved glucose tolerance. Intermittent training (HF-TNT, HF-NTN) preserved metabolic benefits and reduced triglyceride and cholesterol levels. Notably, hepatic steatosis was significantly alleviated in all training groups but persisted even after detraining. Additionally, HIIT downregulated the expression of lipogenic genes and upregulated the expression of genes involved in β-oxidation. The levels of markers indicating ER stress were attenuated by HIIT, with a sustained reduction during periods of detraining. HIIT-induced metabolic and hepatic improvements persist partially during detraining, despite weight regain. These findings underscore the therapeutic value of continued or periodically repeated physical training in mitigating the adverse effects of an HF diet and preventing the progression of metabolic disorders such as MASLD.