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Maternal Metformin Treatment During Obese Pregnancy Reduces Offspring Fatty Liver and Hepatic Inflammation
Author(s) -
Thomas Hugh,
Berlanga Alba,
Byrne Christopher,
Cagampang Felino
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.123.1
Subject(s) - offspring , pregnancy , medicine , endocrinology , lactation , fatty liver , weaning , insulin resistance , gestational diabetes , gestation , metformin , diabetes mellitus , obesity , biology , disease , genetics
Obesity during pregnancy raises offspring risk of non‐alcoholic fatty liver disease (NAFLD) in adulthood. The anti‐diabetic drug metformin (MET) is prescribed for gestational diabetes treatment, yet long term effects of MET during obese pregnancy on offspring NAFLD risk are unknown. We investigated the impact of maternal MET treatment in obese pregnant mice on glucose tolerance (GT), insulin resistance (IR), body fat (BF%) and NAFLD severity in adult offspring. Female C57/BL6J mice were fed control (C) or high fat (HF) diet 6 weeks prior to mating through pregnancy and lactation. Half the pregnant C and HF dams were given MET in drinking water (250mg/kg bodyweight/day) during pregnancy and lactation. Female offspring were weaned onto C or HF diet, giving 8 offspring groups (C/C, C/HF, HF/C, HF/HF and CMET/C, CMET/HF, HFMET/C and HFMET/HF). At 28 weeks GT tests were performed. Offspring were killed at 30 weeks, BF% assessed by μCT scan and livers collected. Expression of hepatic inflammatory genes was measured by RT‐PCR. IR was determined by HOMA‐IR. NAFLD severity was assessed by histological scoring. Data was analysed by mixed effects model. Offspring of HF dam were fatter and had impaired GT and IR compared to offspring of C dam (p<0.05). Offspring of HF dams treated with MET had reduced body fat (mean effect size (ME) 0.8‐fold, p<0.05), improved GT and IR (ME 1.4‐ and 2.3‐fold respectively, both p<0.01), reduced NAFLD severity and lowered expression of inflammatory genes CCL2 , TLR2 , TLR4 and Osteopontin (p<0.05) vs offspring of untreated HF dams. MET treatment in obese pregnant dams alleviates the developmental priming of metabolic disease in adult offspring. Funded by Diabetes UK