Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice.Metabolism 2013; 62(11):1651-61M
Abstract
OBJECTIVE
This study investigated the effects of dietary methionine restriction (MR) on the progression of established hepatic steatosis in the leptin-deficient ob/ob mouse.
MATERIAL/METHODS
Ten-week-old ob/ob mice were fed diets containing 0.86% (control-fed; CF) or 0.12% methionine (MR) for 14 weeks. At 14 weeks, liver and fat were excised and blood was collected for analysis. In another study, blood was collected to determine in vivo triglyceride (TG) and very-low-density lipoprotein (VLDL) secretion rates. Liver histology was conducted to determine the severity of steatosis. Hepatic TG, free fatty acid levels, and fatty acid oxidation (FAO) were also measured. Gene expression was analyzed by quantitative PCR.
RESULTS
MR reversed the severity of steatosis in the ob/ob mouse. This was accompanied by reduced body weight despite similar weight-specific food intake. Compared with the CF group, hepatic TG levels were significantly reduced in response to MR, but adipose tissue weight was not decreased. MR reduced insulin and HOMA ratios but increased total and high-molecular-weight adiponectin levels. Scd1 gene expression was significantly downregulated, while Acadvl, Hadha, and Hadhb were upregulated in MR, corresponding with increased β-hydroxybutyrate levels and a trend toward increased FAO. The VLDL secretion rate was also significantly increased in the MR mice, as were the mRNA levels of ApoB and Mttp. The expression of inflammatory markers, such as Tnf-α and Ccr2, was also downregulated by MR.
CONCLUSIONS
Our data indicate that MR reverses steatosis in the ob/ob mouse liver by promoting FAO, increasing the export of lipids, and reducing obesity-related inflammatory responses.
MeSH
Pub Type(s)
Journal Article
Research Support, Non-U.S. Gov't
Language
eng
PubMed ID
23928105
Citation
Malloy, Virginia L., et al. "Methionine Restriction Prevents the Progression of Hepatic Steatosis in Leptin-deficient Obese Mice." Metabolism: Clinical and Experimental, vol. 62, no. 11, 2013, pp. 1651-61.
Malloy VL, Perrone CE, Mattocks DA, et al. Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice. Metab Clin Exp. 2013;62(11):1651-61.
Malloy, V. L., Perrone, C. E., Mattocks, D. A., Ables, G. P., Caliendo, N. S., Orentreich, D. S., & Orentreich, N. (2013). Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice. Metabolism: Clinical and Experimental, 62(11), pp. 1651-61. doi:10.1016/j.metabol.2013.06.012.
Malloy VL, et al. Methionine Restriction Prevents the Progression of Hepatic Steatosis in Leptin-deficient Obese Mice. Metab Clin Exp. 2013;62(11):1651-61. PubMed PMID: 23928105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR
T1 - Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice.
AU - Malloy,Virginia L,
AU - Perrone,Carmen E,
AU - Mattocks,Dwight A L,
AU - Ables,Gene P,
AU - Caliendo,Nicholas S,
AU - Orentreich,David S,
AU - Orentreich,Norman,
Y1 - 2013/08/05/
PY - 2013/02/28/received
PY - 2013/05/30/revised
PY - 2013/06/27/accepted
PY - 2013/8/10/entrez
PY - 2013/8/10/pubmed
PY - 2014/1/7/medline
KW - ALT
KW - AST
KW - Acac
KW - Acadvl
KW - Adiponectin
KW - ApoB
KW - C-C chemokine receptor-2
KW - CF
KW - Ccr2
KW - Cd 36
KW - Chrebp
KW - Cpt1a
KW - Dgat
KW - EGF-like module-containing mucin-like hormone receptor-like 1
KW - Emr1
KW - FAO
KW - FFA
KW - Fasn
KW - Fatty acid oxidation
KW - Fatty liver
KW - GSH
KW - Gpam
KW - HDL
KW - HFD
KW - HMW
KW - HOMA
KW - Hadha and Hadhb
KW - IL6
KW - IR
KW - Inflammation
KW - Itgax
KW - LDL
KW - Lxr
KW - MR
KW - Mttp
KW - NAFLD
KW - NASH
KW - Pklr
KW - Pnpla2
KW - Pnpla3
KW - Pparα
KW - Pparγ
KW - ROS
KW - Scd1
KW - Srebf1
KW - TG
KW - TNF-α
KW - Triglyceride
KW - VLDL
KW - acetyl-CoA carboxylase
KW - acyl-coenzyme A dehydrogenase, very long chain
KW - alanine aminotransferase
KW - apolipoprotein B
KW - aspartate aminotransferase
KW - carbohydrate regulatory binding protein
KW - carnitine palmitoyltransferase-1a
KW - control-fed
KW - diacylglycerol O-acyltransferase
KW - fatty acid oxidation
KW - fatty acid synthase
KW - free fatty acids
KW - glutathione
KW - hepatic CD36 antigen
KW - high-density lipoprotein
KW - high-fat diet
KW - high-molecular-weight
KW - homeostasis model assessment
KW - hydroxyacyl-coenzyme A dehydrogenase/3-ketoacyl-coenzyme A thiolase/enoyl-coenzyme A hydratase (trifunctional protein), alpha and beta subunits, respectively
KW - insulin resistance
KW - integrin alpha X
KW - interleukin-6
KW - liver X-receptor
KW - low-density lipoprotein
KW - methionine restriction
KW - microsomal triglyceride transfer protein
KW - mitochondrial glycerol-3-phosphate acyltransferase
KW - non-alcoholic fatty liver disease
KW - non-alcoholic steatohepatitis
KW - ob/ob
KW - obese mouse
KW - patatin-like phospholipase domain containing 2
KW - patatin-like phospholipase domain containing 3
KW - peroxisome proliferator-activated receptor α
KW - peroxisome proliferator-activated receptor γ
KW - pyruvate kinase-liver and red blood cell
KW - reactive oxygen species
KW - stearoyl-coenzyme A desaturase-1
KW - sterol regulatory element binding transcription factor 1
KW - triglycerides
KW - tumor necrosis factor-α
KW - very-low-density lipoprotein
SP - 1651
EP - 61
JF - Metabolism: clinical and experimental
JO - Metab. Clin. Exp.
VL - 62
IS - 11
N2 - OBJECTIVE: This study investigated the effects of dietary methionine restriction (MR) on the progression of established hepatic steatosis in the leptin-deficient ob/ob mouse. MATERIAL/METHODS: Ten-week-old ob/ob mice were fed diets containing 0.86% (control-fed; CF) or 0.12% methionine (MR) for 14 weeks. At 14 weeks, liver and fat were excised and blood was collected for analysis. In another study, blood was collected to determine in vivo triglyceride (TG) and very-low-density lipoprotein (VLDL) secretion rates. Liver histology was conducted to determine the severity of steatosis. Hepatic TG, free fatty acid levels, and fatty acid oxidation (FAO) were also measured. Gene expression was analyzed by quantitative PCR. RESULTS: MR reversed the severity of steatosis in the ob/ob mouse. This was accompanied by reduced body weight despite similar weight-specific food intake. Compared with the CF group, hepatic TG levels were significantly reduced in response to MR, but adipose tissue weight was not decreased. MR reduced insulin and HOMA ratios but increased total and high-molecular-weight adiponectin levels. Scd1 gene expression was significantly downregulated, while Acadvl, Hadha, and Hadhb were upregulated in MR, corresponding with increased β-hydroxybutyrate levels and a trend toward increased FAO. The VLDL secretion rate was also significantly increased in the MR mice, as were the mRNA levels of ApoB and Mttp. The expression of inflammatory markers, such as Tnf-α and Ccr2, was also downregulated by MR. CONCLUSIONS: Our data indicate that MR reverses steatosis in the ob/ob mouse liver by promoting FAO, increasing the export of lipids, and reducing obesity-related inflammatory responses.
SN - 1532-8600
UR - https://www.unboundmedicine.com/medline/citation/23928105/Methionine_restriction_prevents_the_progression_of_hepatic_steatosis_in_leptin_deficient_obese_mice_
L2 - https://linkinghub.elsevier.com/retrieve/pii/S0026-0495(13)00193-5
DB - PRIME
DP - Unbound Medicine
ER -
