A new study has demonstrated that 15 weeks of moderate treadmill exercise improved liver lipid droplet regulation in mice fed a high-fat diet, including increased lysosomal acid lipase (LAL) activity, which is reduced in patients with LAL deficiency (LAL-D).

The study, published in Nutrients, found that exercise prevented the high-fat diet (HFD)-induced liver fat deposits and liver injury in the mice.

“In the current study, we observed that HFD decreased the level of LAL, whereas exercise reversed the protein levels of LAL in HFD mice,” the authors wrote. “Our study also demonstrates the benefit of exercise on improving LD degradation through enhancing lysosomal function (lysosomal-autophagosome fusion, acidification, acid lipase amounts) during the later stages of lipophagy.”

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The research team divided 24 male mice into 4 groups: normal sedentary diet, normal diet with exercise, high-fat sedentary diet, and high-fat diet with exercise. Over a 15-week period, the mice in the exercise groups were trained with increasing exercise demand. Blood samples were periodically taken from all mice for analysis and liver tissues were evaluated post-sacrifice.

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The results showed the development of nonalcoholic fatty liver disease characteristics in the mice fed the HFD, which were reversed in the mice doing moderate treadmill exercise.

The team also evaluated levels of protein molecules regulating hepatic lysosomal function, finding that the HFD decreased levels of LAL while exercise increased LAL levels. In addition, they found that HFD increased lipid droplet size, while exercise reduced their size and increased the number of small lipid droplets.

Previous studies have shown that using gene or enzyme methods to reverse LAL expression in LAL-D mice could reduce excess lipid storage in the liver. The authors note that their study shows the ability of 15 weeks of exercise to improve lipid droplet degradation as well as lysosomal function in the later stages of lipophagy.


Yang Y, Li X, Liu Z, et al. Moderate treadmill exercise alleviates NAFLD by regulating the biogenesis and autophagy of lipid droplet. Nutrients. Published online November 20, 2022. doi:10.3390/nu14224910