title: Dietary protein restriction induces steatohepatitis and alters leptin/signal transducers and activators of transcription 3 signaling in lactating rats.
abstract: Dietary protein restriction during lactation affects lipid metabolism and food intake in rats. The goals of this study were to determine the effect of a low-protein diet on a liver damage in lactating rats, to determine whether dietary protein restriction of lactating dams affects the liver health of their offspring and to elucidate the molecular mechanisms underlying the development of hepatic damage. Lactating Sprague-Dawley rats were fed either a control 20% protein diet or an 8% low-protein diet for 11 or 23 days, respectively. After weaning, the offspring were continuously fed either the same control diet or the low-protein diet for an additional 22 days. Feeding a low-protein diet during lactation caused steatohepatitis with severe steatosis, lobular inflammation, ballooning degeneration and fibrosis. Offspring nourished by dams fed a low-protein diet showed simple hepatic steatosis. Combined effects of increased lipogenesis, decreased fatty acid oxidation and impaired very-low-density lipoprotein secretion were responsible for the development of hepatic steatosis. Hepatic up-regulation of genes linked to oxidative stress including nicotinamide adenine dinucleotide phosphate oxidase, inflammation and fibrogenesis supports the development of steatohepatitis in protein-restricted lactating rats. Furthermore, protein-restricted lactating rats showed activation of the leptin/signal transducers and activators of the transcription 3 signaling pathway. Taken together, oxidative stress induced by up-regulation of nicotinamide adenine dinucleotide phosphate oxidase with activation of leptin/signal transducers and activators of the transcription 3 signaling was responsible for development of steatohepatitis in protein-restricted lactating rats. Our findings suggest that protein malnutrition has a potential to induce steatohepatitis/hepatic steatosis in lactating mothers and infants during breast-feeding.
authors.affiliation: Department of Molecular Biotechnology, WCU-RNNM, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Duk-Hwa
authors.initials: DH
authors.lastname: Kwon
authors.forename: Wanseok
authors.initials: W
authors.lastname: Kang
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Nam
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Lee
authors.forename: In Young
authors.initials: IY
authors.lastname: Lee
authors.forename: Hye Joung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Panchamoorthy
authors.initials: P
authors.lastname: Rajasekar
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Myunggi
authors.initials: M
authors.lastname: Baik
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D004044:Dietary Proteins / Q000008:administration & dosage*; D005234:Fatty Liver / Q000503:physiopathology*; D005260:Female; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007774:Lactation / Q000502:physiology; D020738:Leptin / Q000097:blood / Q000235:genetics*; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D004044:Dietary Proteins; D020738:Leptin; D008079:Lipoproteins, VLDL; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat