Gender-specific programmed hepatic lipid dysregulation in intrauterine growth-restricted offspring.
OBJECTIVE
Intrauterine growth restriction demonstrates increased risk of adult metabolic syndrome. The associated hyperlipidemia results from obesity or programmed metabolic abnormalities. Because lipid homeostasis is regulated by the liver, we hypothesized that hepatic structure and lipid content in intrauterine growth restriction would reflect a primary lipid dysfunction.


METHODS
From 10 days to term gestation, control pregnant rats received ad libitum diet; study rats were 25% food-restricted (FR). All dams received ad libitum diet throughout lactation. At 3 weeks of age, hepatic lobule size and lipid profile of the pups were determined.


RESULTS
At 3 weeks of age, body and liver weights of the pups were comparable with controls, although with reduced hepatic lobule size. FR males had increased hepatic triglyceride and cholesterol content with elevated sterol regulatory element-binding protein-1c, fatty acid synthase, and lipoprotein lipase expression; FR females exhibited decreased hepatic cholesterol levels. Plasma lipid levels were unchanged in FR males and females.


CONCLUSIONS
Developmental programming results in sex-dependent altered lipid metabolism with increased risk in males.
Choi
Gyu Yeon
GY
Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, CA, USA.
Tosh
Darran N
DN
Garg
Ambica
A
Mansano
Roy
R
Ross
Michael G
MG
Desai
Mina
M
D000818:Animals; D002784:Cholesterol / Q000032:analysis; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D064429:Fatty Acid Synthases / Q000096:biosynthesis; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000503:physiopathology*; D050356:Lipid Metabolism / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000473:pathology*; D008297:Male; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D039401:Prenatal Nutritional Physiological Phenomena; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis; D014280:Triglycerides / Q000032:analysis
C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D002784:Cholesterol; D064429:Fatty Acid Synthases; D008071:Lipoprotein Lipase