Maternal PPAR gamma protects nursing neonates by suppressing the production of inflammatory milk.
Lactation is a highly demanding lipid synthesis and transport process that is crucial for the development of newborn mammals. While PPAR gamma 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 PPAR gamma 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 PPAR gamma 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 PPAR gamma-deficient mothers. Therefore, maternal PPAR gamma 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.
Wan
Yihong
Y
Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Saghatelian
Alan
A
Chong
Ling-Wa
LW
Zhang
Chun-Li
CL
Cravatt
Benjamin F
BF
Evans
Ronald M
RM
D000505:Alopecia / Q000209:etiology / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006130:Growth Disorders / Q000209:etiology; D007249:Inflammation / Q000209:etiology; D018836:Inflammation Mediators / Q000378:metabolism*; D007774:Lactation / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008892:Milk / Q000378:metabolism* / Q000633:toxicity; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy
D005230:Fatty Acids, Nonesterified; D018836:Inflammation Mediators; D047495:PPAR gamma; D001092:Arachidonate 12-Lipoxygenase