Maternal obesity increases the risk and severity of NAFLD in offspring

Hagström, Hannes; Simon, Tracey G.; Roelstraete, Björn; Stephansson, Olof; Söderling, Jonas; Ludvigsson, Jonas F.

doi:10.1016/j.jhep.2021.06.045

Cited by 61 publications

(49 citation statements)

References 35 publications

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“…In a recent systematic review, a prepregnancy obesity was clearly related to an increased risk of pediatric MAFLD [ 39 ]. This association has been confirmed in a recent Swedish study [ 40 ]. In the previous systematic review, pregestational or gestational diabetes and abnormal birth anthropometrics were not definitively associated with pediatric MAFLD.…”

Section: General Information On Pediatric Mafldsupporting

confidence: 78%

Metabolic Fatty Liver Disease in Children: A Growing Public Health Problem

et al. 2021

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Metabolic-associated fatty liver disease (MAFLD), previously called nonalcoholic fatty liver diseases (NAFLD), is one of the most important causes of chronic liver disease worldwide and will likely become the leading cause of end-stage liver disease in the decades ahead. MAFLD covers a continuum of liver diseases from fatty liver to nonalcoholic steatohepatitis (NASH), liver fibrosis/cirrhosis and hepatocellular cancer. Importantly, the growing incidence of overweight and obesity in childhood, 4% in 1975 to 18% in 2016, with persisting obesity complications into adulthood, is likely to be harmful by increasing the incidence of severe MAFLD at an earlier age. Currently, MAFLD is the leading form of chronic liver disease in children and adolescents, with a global prevalence of 3 to 10%, pointing out that early diagnosis is therefore crucial. In this review, we highlight the current knowledge concerning the epidemiology, risk factors and potential pathogenic mechanisms, as well as diagnostic and therapeutic approaches, of pediatric MAFLD.

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Section: General Information On Pediatric Mafldsupporting

confidence: 78%

Metabolic Fatty Liver Disease in Children: A Growing Public Health Problem

et al. 2021

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“…Only a subset of offspring of obese mothers developed steatosis and an even smaller proportion developed fibrosis and NASH. This is likely representative of what happens in clinical reality [ 14 ]. It is, therefore, crucial to identify and follow the individuals at risk as early as possible.…”

Section: Discussionmentioning

confidence: 99%

“…The rising global obesity rate is a major public health concern for future generations. Obesity of the mother places the offspring at risk for developing NAFLD [ 14 ]. However, the mechanisms involved remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, murine studies have shown that pups born to obese mothers exhibit an increased risk of developing liver diseases such as steatosis and signs of hepatitis such as increased inflammatory markers and fibrosis [ 12 , 13 ]. A recent epidemiological study confirmed these results and demonstrated that the offspring of obese mothers had a threefold higher risk of developing non-alcoholic liver disease (NAFLD) in adulthood [ 14 ].…”

Section: Introductionmentioning

confidence: 92%

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Impact of Maternal Obesity on Liver Disease in the Offspring: A Comprehensive Transcriptomic Analysis and Confirmation of Results in a Murine Model

et al. 2022

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The global obesity epidemic particularly affects women of reproductive age. Offspring of obese mothers suffer from an increased risk of liver disease but the molecular mechanisms involved remain unknown. We performed an integrative genomic analysis of datasets that investigated the impact of maternal obesity on the hepatic gene expression profile of the offspring in mice. Furthermore, we developed a murine model of maternal obesity and studied the development of liver disease and the gene expression profile of the top dysregulated genes by quantitative real-time polymerase chain reaction (qPCR). Our data are available for interactive exploration on our companion webpage. We identified five publicly available datasets relevant to our research question. Pathways involved in metabolism, the innate immune system, the clotting cascade, and the cell cycle were consistently dysregulated in the offspring of obese mothers. Concerning genes involved in the development of liver disease, Egfr, Vegfb, Wnt2, Pparg and six other genes were dysregulated in multiple independent datasets. In our own model, we observed a higher tendency towards the development of non-alcoholic liver disease (60 vs. 20%) and higher levels of alanine aminotransferase (41.0 vs. 12.5 IU/l, p = 0.008) in female offspring of obese mothers. Male offspring presented higher levels of liver fibrosis (2.4 vs. 0.6% relative surface area, p = 0.045). In a qPCR gene expression analysis of our own samples, we found Fgf21, Pparg, Ppard, and Casp6 to be dysregulated by maternal obesity. Maternal obesity represents a looming threat to the liver health of future generations. Our comprehensive transcriptomic analysis will help to better understand the mechanisms of the development of liver disease in the offspring of obese mothers and can give rise to further explorations.

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“…This truly global phenomenon affects women of childbearing age particularly and thus more and more children are born to obese mothers every year (2). Large-scale epidemiological studies have shown that maternal obesity has deleterious effects on offspring health such as increased risk for obesity, liver steatosis and even certain types of cancers (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%