Dietary methionine restriction in mice elicits an adaptive cardiovascular response to hyperhomocysteinemia.
Dietary methionine restriction (MR) in rodents increased lifespan despite higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia, which are symptoms associated with increased risk for cardiovascular disease. We investigated this paradoxical effect of MR on cardiac function using young, old, and apolipoprotein E-deficient (ApoE-KO) mice. Indeed, MR animals exhibited higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia with a molecular pattern consistent with cardiac stress while maintaining the integrity of cardiac structure. Baseline cardiac function, which was measured by non-invasive electrocardiography (ECG), showed that young MR mice had prolonged QRS intervals compared with control-fed (CF) mice, whereas old and ApoE-KO mice showed similar results for both groups. Following β-adrenergic challenge, responses of MR mice were either similar or attenuated compared with CF mice. Cardiac contractility, which was measured by isolated heart retrograde perfusion, was similar in both groups of old mice. Finally, the MR diet induced secretion of cardioprotective hormones, adiponectin and fibroblast growth factor 21 (FGF21), in MR mice with concomitant alterations in cardiac metabolic molecular signatures. Our findings demonstrate that MR diet does not alter cardiac function in mice despite the presence of hyperhomocysteinemia because of the adaptive responses of increased adiponectin and FGF21 levels.
The Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY.
Gene P
GP
Ables
The Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY.
Amadou
A
Ouattara
Mouse Specifics, Inc., Quincy, MA.
Thomas G
TG
Hampton
The Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY.
Diana
D
Cooke
The Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY.
Frantz
F
Perodin
The Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY.
Ines
I
Augie
The Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY.
David S
DS
Orentreich
D000222:Adaptation, Physiological; D052242:Adiponectin / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004032:Diet; D004198:Disease Susceptibility; D005346:Fibroblast Growth Factors / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D008715:Methionine; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction
D052242:Adiponectin; D000318:Adrenergic beta-Agonists; D001057:Apolipoproteins E; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D008715:Methionine