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Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Circulating levels of the cytokines IL10, IFNγ and resistin in an obese mouse model of developmental programming
M A Kępczyńska1, E T Wargent1, M A Cawthorne1
1Clore Laboratory, University of Buckingham, Buckingham, UK.
Insights
Maternal high-fat diet during pregnancy alters key metabolic factors in the mother, potentially programming offspring for metabolic disease. Understanding these maternal changes is crucial for developing interventions to prevent future health issues in children.
Area of Science:
- Reproductive biology
- Metabolic disease research
- Developmental programming
Background:
- Early life environment significantly influences offspring's metabolic health.
- Maternal obesity and diet are linked to increased offspring susceptibility to metabolic disorders.
- Identifying specific maternal factors mediating these effects is critical for clinical interventions.
Purpose of the Study:
- To investigate which maternal metabolic factors, altered by a high-fat diet, induce adverse metabolic programming in offspring.
- To use a diet-induced obese mouse model to identify these mediating factors.
Main Methods:
- Female C57Bl/6 mice were fed either a control chow or a high-fat diet for 10 weeks pre-mating and throughout gestation.
- Maternal body weight, composition, glucose tolerance, and plasma levels of insulin, adiponectin, RBP4, leptin, resistin, and inflammatory cytokines were measured at gestational day 18.
Main Results:
- High-fat-fed dams exhibited increased body weight, fat mass, fasting blood glucose, and plasma insulin compared to control dams.
- Obese dams showed reduced plasma adiponectin and resistin but increased levels of inflammatory cytokines (IL6, IL10, IFNγ).
- Pregnancy high-fat feeding alters maternal plasma adipokines and adipocytokines.
Conclusions:
- Maternal high-fat diet during pregnancy induces significant metabolic and inflammatory changes in the dam.
- These altered maternal factors may directly impact fetal development, potentially leading to metabolic programming.
- Further research is needed to confirm the direct transfer and impact of these factors on fetal programming.
Abstract:
An infant's early developmental environment plays a pivotal role in the programming of its physiological phenotype. The identification of the factors in the maternal environment that mediate the effects of maternal obesity and diet is essential to the development of clinical intervention strategies. Maternal hyperglycaemia, hyperinsulinaemia, hypertriglyceridaemia, hyperleptinaemia and altered inflammatory cytokines concentrations are potentially important predictive factors of her future offspring's susceptibility to metabolic disease. Using a diet-induced obese mouse model, we have investigated which of these maternal factors could induce adverse metabolic programming in the offspring. Female C57Bl/6 mice were fed either laboratory chow (10% fat) or high fat diet (42% fat) for 10 weeks before mating and throughout gestation. At day 18 of pregnancy, maternal body weight, body composition and glucose tolerance were measured, as well as plasma insulin, adiponectin, RBP4, leptin, resistin and the inflammatory cytokines (IL6, IL10, IL12, IL1β, IFNγ, KC, TNF-α). At day 18 of pregnancy, high fat-fed dams were significantly heavier than the chow dams and had increased fat mass. High fat-fed dams had higher 5 h fasting blood glucose than chow dams and elevated plasma insulin. Although the obese dams had both reduced plasma adiponectin and resistin levels compared with lean dams, their plasma IL6, IL10 and IFNγ levels were all increased. High fat feeding in pregnancy leads to altered plasma concentrations of both adipokines and adipocytokines in the dam that may directly pass to the fetus and affect their development.

