title: Methionine-restricted C57BL/6J mice are resistant to diet-induced obesity and insulin resistance but have low bone density.
abstract: Dietary methionine restriction (MR) extends lifespan, an effect associated with reduction of body weight gain, and improvement of insulin sensitivity in mice and rats as a result of metabolic adaptations in liver, adipose tissue and skeletal muscle. To test whether MR confers resistance to adiposity and insulin resistance, C57BL/6J mice were fed a high fat diet (HFD) containing either 0.86% methionine (control fed; CF) or 0.12% methionine (methionine-restricted; MR). MR mice on HFD had lower body weight gain despite increased food intake and absorption efficiency compared to their CF counterparts. MR mice on HFD were more glucose tolerant and insulin sensitive with reduced accumulation of hepatic triglycerides. In plasma, MR mice on HFD had higher levels of adiponectin and FGF21 while leptin and IGF-1 levels were reduced. Hepatic gene expression showed the downregulation of Scd1 while Pparg, Atgl, Cd36, Jak2 and Fgf21 were upregulated in MR mice on HFD. Restriction of growth rate in MR mice on HFD was also associated with lower bone mass and increased plasma levels of the collagen degradation marker C-terminal telopeptide of type 1 collagen (CTX-1). It is concluded that MR mice on HFD are metabolically healthy compared to CF mice on HFD but have decreased bone mass. These effects could be associated with the observed increase in FGF21 levels.
authors.affiliation: Orentreich Foundation for the Advancement of Science, Cold Spring-on-Hudson, New York, United States of America. gables@orentreich.org
authors.forename: Gene P
authors.initials: GP
authors.lastname: Ables
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Perrone
authors.forename: David
authors.initials: D
authors.lastname: Orentreich
authors.forename: Norman
authors.initials: N
authors.lastname: Orentreich
mesh_terms: D052242:Adiponectin / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D059305:Diet, High-Fat; D060467:Disease Resistance / Q000187:drug effects / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000097:blood; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005951:Glucose Tolerance Test; D006652:Histological Techniques; D007333:Insulin Resistance / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008715:Methionine / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology*; D060888:Real-Time Polymerase Chain Reaction; D045442:Rotarod Performance Test
chemical_list: D052242:Adiponectin; D024042:Collagen Type I; D017931:DNA Primers; D020738:Leptin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D008715:Methionine