Maternal Socs3 knockdown attenuates postnatal obesity caused by an early life environment of maternal obesity and intrauterine overnutrition in progeny mice

Abstract

Pathological states in the early life environment of mammalian offspring, including maternal obesity and intrauterine overnutrition, can induce obesity and metabolic disorder later in life. Leptin resistance caused by upregulation of Socs3 in the hypothalamus of offspring was believed to be the main mechanism of this effect. In this study, obese mother (OM) and lean mother (LM) models were generated by feeding C57BL/6N female mice a high‐fat diet or standard lean diet, respectively. Additionally, an obese mother with intervention (OMI) model was generated by injecting the high‐fat diet group with Socs3‐shRNA lentivirus during early pregnancy. The offspring of the groups was correspondingly named OM‐F1, LM‐F1, and OMI‐F1, representing progeny mouse models of different early life environments. The offspring were fed a high‐fat diet to test their propensity for obesity. The body weight, food intake and fat accumulation were higher, while glucose intolerance and insulin resistance were worse in the OM‐F1 group than LM‐F1 group. By contrast, the obesity phenotype, hyperphagia and metabolic disorder were alleviated in the OMI‐F1 group compared with the OM‐F1 group. The mechanism was identified that downregulation of hypothalamic SOCS3 resulted in an increased level of p‐STAT3 and p‐JAK2, which ameliorated the leptin resistance and restored the lean expression of appetite regulatory genes (Pomc and Agrp) in hypothalamus of OMI‐F1 group. Taken together, these results indicate that reducing maternal Socs3 expression during pregnancy can attenuate obesity caused by the early life environment in mice, which may inspire therapies that enable obese mothers to bear metabolically healthy children.

Maternal inulin alleviates high-fat diet-induced lipid disorder in offspring by epigenetically modulating hypothalamus feeding circuit-related genes

“…74 Zhu et al provided evidence showing that maternal Socs3 knockdown attenuates the obesity phenotype and metabolic disorder in offspring. 75 Our results showed that the MHFD offspring exhibited high serum leptin levels. However, hypermethylation and lower expression of the hypothalamic Lepr gene were observed in the offspring from the MHFD dams compared with the offspring from the control dams.…”

“…74 Zhu et al provided evidence showing that maternal Socs3 knockdown attenuates the obesity phenotype and metabolic disorder in offspring. 75…”

Is developmental plasticity triggered by DNA methylation changes in the invasive cane toad (Rhinella marina)?

“…AKTIP‐A mouse mutants show developmental abnormalities (Anselme et al., 2007 ). HSPB6 is involved in the regulation of angiogenesis (Vafiadaki et al., 2020 ), SCNN1G plays a role in water homeostasis (Hobbs et al., 2013 ), while SOCS3 is involved in the regulation of food intake (Zhu et al., 2021 ). DNA methylation patterns of 5′‐flanking regions have been shown to correlate with gene expression, at least for SCNN1G (Pierandrei et al., 2021 ).…”

Is developmental plasticity triggered by DNA methylation changes in the invasive cane toad (Rhinella marina)?

“…These DMRs were found within the gene bodies of HSPB6 , PGS1 , SCNN1G , SOCS3 , as well as two uncharacterised genes. HSPB6 is involved in the regulation of angiogenesis (Vafiadaki, Arvanitis, Eliopoulos, Kranias, & Sanoudou, 2020), SCNN1G plays a role in water homeostasis (Hobbs et al, 2013), while SOCS3 is involved in the regulation of food intake (Zhu et al, 2021). DNA methylation patterns of 5’-flanking regions have been shown to correlate with gene expression, at least for SCNN1G (Pierandrei et al, 2021).…”