Sex difference in liver diseases: How preclinical models help to dissect the sex-related mechanisms sustaining NAFLD and hepatocellular carcinoma

Smiriglia, Alfredo; Lorito, Nicla; Serra, Marina; Perra, Andrea; Morandi, Andrea; Kowalik, Marta Anna

doi:10.1016/j.isci.2023.108363

Cited by 7 publications

(2 citation statements)

References 218 publications

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“…NAFLD is the most common disease in industrialized countries, characterized by excessive storage of triglycerides (TAGs) in the hepatocyte (above 5%), with its progression characterized by changes such as inflammation and hepatocellular ballooning [18]. Thus, it is possible to observe that menopausal women, probably because of the lack of estrogen action, display an increased prevalence of NAFLD and, consequently, more severe progressions of this disease [1,21]. This progression is also observed in animal models of male ApoE KO mice and ovariectomized female mice [12,22].…”

Section: Introductionmentioning

confidence: 99%

Strength Training Protects High-Fat-Fed Ovariectomized Mice against Insulin Resistance and Hepatic Steatosis

Santos,

Silva,

Alves

et al. 2024

IJMS

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Menopause is characterized by a reduction in sex hormones in women and is associated with metabolic changes, including fatty liver and insulin resistance. Lifestyle changes, including a balanced diet and physical exercise, are necessary to prevent these undesirable changes. Strength training (ST) has been widely used because of the muscle and metabolic benefits it provides. Our study aims to evaluate the effects of ST on hepatic steatosis and insulin resistance in ovariectomized mice fed a high-fat diet (HFD) divided into four groups as follows: simulated sedentary surgery (SHAM-SED), trained simulated surgery (SHAM-EXE), sedentary ovariectomy (OVX-SED), and trained ovariectomy (OVX-EXE). They were fed an HFD for 9 weeks. ST was performed thrice a week. ST efficiently reduced body weight and fat percentage and increased lean mass in OVX mice. Furthermore, ST reduced the accumulation of ectopic hepatic lipids, increased AMPK phosphorylation, and inhibited the de novo lipogenesis pathway. OVX-EXE mice also showed a better glycemic profile, associated with greater insulin sensitivity identified by the euglycemic–hyperinsulinemic clamp, and reduced markers of hepatic oxidative stress compared with sedentary animals. Our data support the idea that ST can be indicated as a non-pharmacological treatment approach to mitigate metabolic changes resulting from menopause.

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Section: Introductionmentioning

confidence: 99%

Strength Training Protects High-Fat-Fed Ovariectomized Mice against Insulin Resistance and Hepatic Steatosis

Santos,

Silva,

Alves

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Considering sex-related differences when planning mouse experiments for studying liver disease and liver cancer is critical and high-quality experiments always should be conducted in both sexes. 11 Systematic experiments involving (exogenous) estrogen, androgens, and specific models such as gonadectomized males can help to explore the roles of sex hormones, shedding light on mechanisms. There is an ongoing need for assessment of sex-dependent markers to personalize treatments.…”

mentioning

confidence: 99%