Maternal PPARγ protects nursing neonates by suppressing the production of inflammatory milk

Genes and Development - Tập 21 Số 15 - Trang 1895-1908 - 2007
Yihong Wan1, Alan Saghatelian, Ling-Wa Chong, Chun‐Li Zhang, Benjamin F. Cravatt, Ronald M. Evans
1Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Tóm tắt

Lactation is a highly demanding lipid synthesis and transport process that is crucial for the development of newborn mammals. While PPARγ is known to promote adipogenesis and lipogenesis in adipose tissue, its role in the lactating mammary gland is unexplored. Here, we report that a targeted deletion of PPARγ in mice results in the production of “toxic milk” containing elevated levels of inflammatory lipids. Surprisingly, ingestion of this “toxic milk” causes inflammation, alopecia, and growth retardation in the nursing neonates. Genomic profiling reveals that PPARγ deficiency leads to increased expression of lipid oxidation enzymes in the lactating mammary gland. Consistently, metabolomic profiling detects increased levels of oxidized free fatty acids in the pups nursed by PPARγ-deficient mothers. Therefore, maternal PPARγ is pivotal for maintaining the quality of milk and protecting the nursing newborns by suppressing the production of inflammatory lipids in the lactating mammary gland.

Từ khóa


Tài liệu tham khảo

Allen,, 1991, Studies in human lactation: Milk composition and daily secretion rates of macronutrients in the first year of lactation, Am. J. Clin. Nutr., 54, 69, 10.1093/ajcn/54.1.69

10.1016/S1097-2765(00)80209-9

Bol,, 2002, Cyclooxygenase-2 overexpression in the skin of transgenic mice results in suppression of tumor development, Cancer Res., 62, 2516

10.1073/pnas.96.2.541

10.1073/pnas.89.1.217

10.1002/gene.1030

10.1172/JCI200113171

10.1016/0092-8674(95)90193-0

10.1073/pnas.94.9.4312

10.1126/science.294.5548.1871

10.1186/bcr441

10.1073/pnas.2536828100

10.1038/nm956

10.1038/22572

10.1038/34184

10.1101/gad.1115203

10.1006/dbio.2000.0106

10.1073/pnas.94.9.4318

10.1084/jem.193.6.741

10.1073/pnas.2336090100

10.1016/S1097-2765(00)80210-5

10.1074/jbc.270.22.12953

Medina-Gomez,, 2005, The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-γ2 isoform, Diabetes, 54, 1706, 10.2337/diabetes.54.6.1706

10.1038/nm0597-562

10.1073/pnas.96.16.8849

10.1046/j.1523-1747.2003.12473.x

10.1046/j.0022-202x.2001.01377.x

10.1016/S0092-8674(00)81574-3

10.1034/j.1600-0625.2001.100601.x

10.1146/annurev.nutr.17.1.159

10.1126/science.285.5431.1276

10.1056/NEJM199908123410706

10.1016/S1534-5807(03)00274-0

10.1038/34178

10.1016/S1097-2765(00)80211-7

10.1101/gad.1167804

10.1021/bi0480335

10.1111/1523-1747.ep12551679

10.1194/jlr.M300045-JLR200

10.1172/JCI28898

10.1021/ac051437y

10.1101/gad.205701

Stenn,, 2001, Controls of hair follicle cycling, Physiol. Rev., 81, 449, 10.1152/physrev.2001.81.1.449

10.1016/S1471-4914(02)00025-4

10.1016/0092-8674(94)90006-X

10.1016/S0092-8674(00)81575-5

10.1172/JCI200420964

10.1006/dbio.2002.0669

10.1021/jm950395a

10.1016/S0002-9440(10)63456-6

10.1073/pnas.0403652101

Thông tin
Thông tin xuất bản

Genes and Development

Tập 21 Số 15

1895-1908

Thông tin tác giả