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Gulati et al. Metab Target Organ Damage 2024;4:9 https://dx.doi.org/10.20517/mtod.2023.45 Page 11 of 17

others remains less well known.

Sedentary behavior among patients is not only associated with obesity, but also with MASLD, and this has
[66]
been demonstrated in various populations . Utilizing the 2007-2016 United States NHANES, Kim et al.
included a group of 24,588 multiethnic individuals and found that sedentary behavior is an independent
predictor of MASLD, and that physical activity of 150 minutes or more per week demonstrated 40 percent
[71]
lower odds of MASLD . Among a group of 2,892 multiethnic adults in the United States, with a 35.6%
prevalence of MASLD, Heredia et al. found that high adherence to United States dietary recommendations
[72]
and more physical activity were associated with reduced odds of MASLD . In a separate study, Heredia et
al. investigated Hispanic adults from the 2017-2018 NHANES and found that higher levels of physical
[73]
activity were associated with a lower risk of MASLD . Television viewing time was found to be
independently associated with a higher fatty liver index in Finnish adults . Similarly, device usage time,
[74]
including computers and mobile devices, was found to be associated with increased odds of MASLD in
Chinese adults . Besides the obvious benefit of weight loss, physical activity and exercise reduce one’s risk
[75]
of MASLD by improving peripheral insulin sensitivity, increasing very-low-density-lipoprotein clearance
[76]
which enables the liver to export triglycerides, and also by improving appetite control .

These behavioral risk factors, including high-fat, high-carbohydrate diet and sedentary behavior, are risk
factors for all populations to develop MASLD, regardless of race and ethnicity. Understanding barriers to
health-promoting behaviors, which include Mediterranean, high-protein, and low-carbohydrate diets and
increased physical activity, in all populations vulnerable to MASLD will allow the design of targeted
interventions.

Contribution of epigenetics to predominance of MASLD
Epigenetics have been found to play a significant role in the development of MASLD. There is increasing
evidence that maternal pre-pregnancy obesity, diabetes, weight gain during pregnancy, and gestational
[77]
diabetes are associated with greater amounts of fatty acids in the fetus and MASLD in childhood . In
addition, maternal and paternal obesity are associated with DNA methylation changes in newborn cord
blood that are not seen in newborns of non-obese parents. Studies have found that maternal obesity,
diabetes, or Western diet consumption leads to an unfavorable intrauterine environment in which hepatic
[78]
mitochondrial function in the fetal liver is more vulnerable to damage . These exposures can thus bring
about fetal metabolic reprogramming via epigenetic mechanisms, which contribute to the risk of MASLD in
the child’s lifetime. The prevalence of gestational diabetes is two to three times higher in Hispanic
populations than in the general population, which may contribute to an increased prevalence of MASLD in
Hispanic populations . Populations with obesity and gestational diabetes are more likely to influence their
[79]
offspring’s genes and increase their risk of developing obesity and metabolic syndrome as well. This
contributes to a perpetual cycle as one generation increases the risk of MASLD in the next generation.
Determining populations with these risk factors can help determine which populations are more vulnerable
to MASLD developing within their offspring as well.

Contribution of socioeconomic disparities to racial and ethnic disparities in MASLD
Given how interconnected the risk of MASLD is to factors such as diet quality, time and energy for physical
activity, and access to preventative healthcare as discussed above, it is therefore logical that socioeconomic
disparities play a role in racial and ethnic disparities within MASLD. Data from the United States Centers
for Disease Control and Prevention has previously found that within United States populations, higher
socioeconomic status is associated with less obesity prevalence, and vice versa . The same trend has been
[80]
found specifically among Hispanic individuals, as higher household income and higher educational
[81]
attainment are both associated with a lower risk of obesity and a greater chance of weight loss .