Effect of dietary monosodium glutamate on trans fat-induced nonalcoholic fatty liver disease.
The effects of dietary monosodium glutamate (MSG) on trans-fatty acid (TFA)-induced nonalcoholic fatty liver disease (NAFLD) are addressed in an animal model. We used Affymetrix microarray analysis to investigate hepatic gene expression and the contribution of visceral white adipose tissue (WAT) to diet-induced NAFLD. Trans-fat feeding increased serum leptin, FFA, HDL-cholesterol (HDL-C), and total cholesterol (T-CHOL) levels, while robustly elevating the expression of genes involved in hepatic lipogenesis, including the transcription factor sterol-regulatory element binding protein 1c. Histological examination revealed hepatic macrosteatosis in TFA-fed animals. Conversely, dietary MSG at doses similar to human average daily intake caused hepatic microsteatosis and the expression of beta-oxidative genes. Serum triglyceride, FFA, and insulin levels were elevated in MSG-treated animals. The abdominal cavities of TFA- or MSG-treated animals had increased WAT deposition compared with controls. Microarray analysis of WAT gene expression revealed increased lipid biosynthetic gene expression, together with a 50% decrease in the key transcription factor Ppargc1a. A combination of TFA+MSG resulted in the highest levels of serum HDL-C, T-CHOL, and leptin. Microarray analysis of TFA+MSG-treated livers showed elevated expression of markers of hepatic inflammation, lipid storage, cell damage, and cell cycle impairment. TFA+MSG mice also had a high degree of WAT deposition and lipogenic gene expression. Levels of Ppargc1a were further reduced to 25% by TFA+MSG treatment. MSG exacerbates TFA-induced NAFLD.
Collison
Kate S
KS
Cell Biology and Diabetes Research Unit, Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia. kate@kfshrc.edu.sa
Maqbool
Zakia
Z
Saleh
Soad M
SM
Inglis
Angela
A
Makhoul
Nadine J
NJ
Bakheet
Razan
R
Al-Johi
Mohammed
M
Al-Rabiah
Rana
R
Zaidi
Marya Z
MZ
Al-Mohanna
Futwan A
FA
D050154:Adiposity / Q000187:drug effects / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D048429:Cell Size / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage*; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000473:pathology*; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011247:Pregnancy; D012970:Sodium Glutamate / Q000008:administration & dosage* / Q000633:toxicity; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D044242:Trans Fatty Acids / Q000008:administration & dosage* / Q000633:toxicity; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D008055:Lipids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D044242:Trans Fatty Acids; D015534:Trans-Activators; D014157:Transcription Factors; D002784:Cholesterol; D012970:Sodium Glutamate