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Effect of lactational high fat diet and metformin on mid-lactation murine mammary gland gene expression

ABSTRACT: Maternal health and diet can have important consequences for offspring nutrition and metabolic health. Signals are communicated from the mother to the infant during lactation through milk via macronutrients, hormones and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring beginning to wean. We found that lactational HFD increased maternal adipose tissue, mammary gland adipocytes, and altered milk lipid composition causing a higher amount of n-6 long chain fatty acids and lower n-3. Offspring of HFD dams were heavier with more body fat during suckling. Metformin exposure decreased maternal glucose and several amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to recuse from the effects of a maternal HFD during lactation.

ORGANISM(S): Mus musculus

PROVIDER: GSE176118 | GEO | 2021/06/04

REPOSITORIES: GEO

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Project description:Non-steroidal anti-inflammatory drug activated gene 1 (NAG-1) plays some role in reducing obesity in mice overexpressing human NAG-1, even on a high fat diet. Male and female hNAG-1 expressing mice have reduced body weight, increased longevity and metabolic activity. This study investigates the role of hNAG-1 in female reproduction and finds that the female mice have reduced fertility and pup survival after birth. Examination of the mammary glands in these mice suggests that hNAG-1 overexpressing mice have altered mammary epithelial development during pregnancy, including reduced occupancy of the fat pad and increased apoptosis via TUNEL positive cells at lactation day 2. Pups nursing from hNAG-1 overexpressing dams have reduced milk spots compared to pups nursing from WT dams. When CD-1 pups were cross-fostered with hNAG-1 or WT dams; reduced milk volume was observed in pups nursing from hNAG-1 dams compared to pups nursing from WT dams in a lactation challenge study. Milk was isolated from WT and hNAG-1 dams, and the milk was found to have secreted NAG-1 protein (approximately 25ng/mL) from hNAG-1 dams compared to WT dams, which had no detectable NAG-1 in the milk. A decrease in non-esterified free fatty acids in the milk of hNAG-1 dams was observed. Altered milk composition suggests that the pups were receiving inadequate nutrients during perinatal development; to examine this hypothesis serum was isolated from pups and clinical chemistry points were measured. Male and female pups nursing from hNAG-1 dams had reduced serum triglyceride concentrations. Cidea/CIDEA expression was reduced in hNAG-1 mammary glands, and microarray analysis suggests that genes involved in lipid metabolism are differentially expressed in hNAG-1 mammary glands. This study suggests that overexpression of hNAG-1 impairs lactational differentiation and pup survival due to altered milk quality and quantity 4 WT mammary glands on lactation day 2 and 5 hNAG-1 transgenic mice mammary glands on lactation day 2 were used.

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Effect of lactational high fat diet and metformin on mid-lactation murine mammary gland gene expression

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