title: Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress.
abstract: There is growing in vivo evidence that the dipeptide carnosine has protective effects in metabolic diseases. A critical unanswered question is whether its site of action is tissues or plasma. This was investigated using oral carnosine versus β-alanine supplementation in a high-fat diet rat model. Thirty-six male Sprague-Dawley rats received a control diet (CON), a high-fat diet (HF; 60% of energy from fat), the HF diet with 1.8% carnosine (HFcar), or the HF diet with 1% β-alanine (HFba), as β-alanine can increase muscle carnosine without increasing plasma carnosine. Insulin sensitivity, inflammatory signaling, and lipoxidative stress were determined in skeletal muscle and blood. In a pilot study, urine was collected. The 3 HF groups were significantly heavier than the CON group. Muscle carnosine concentrations increased equally in the HFcar and HFba groups, while elevated plasma carnosine levels and carnosine-4-hydroxy-2-nonenal adducts were detected only in the HFcar group. Elevated plasma and urine N(ε)-(carboxymethyl)lysine in HF rats was reduced by ∼50% in the HFcar group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA was decreased by 47% (p < 0.05) in the HFcar group, but not in the HFba group, compared with HF rats. We conclude that plasma carnosine, but not muscle carnosine, is involved in preventing early-stage lipoxidation in the circulation and inflammatory signaling in the muscle of rats.
authors: a Department of Movement and Sport Sciences, Ghent University, Watersportlaan 2, 9000 Ghent, Belgium.
authors: Sanne
authors: S
authors: Stegen
authors: a Department of Movement and Sport Sciences, Ghent University, Watersportlaan 2, 9000 Ghent, Belgium.
authors: Bram
authors: B
authors: Stegen
authors: b Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Giancarlo
authors: G
authors: Aldini
authors: b Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Alessandra
authors: A
authors: Altomare
authors: b Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Luca
authors: L
authors: Cannizzaro
authors: b Department of Pharmaceutical Sciences, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.
authors: Marica
authors: M
authors: Orioli
authors: c VIB Department of Medical Protein Research, Ghent University, Albert Baertsoenkaai 3, 9000 Ghent, Belgium.
authors: Sarah
authors: S
authors: Gerlo
authors: d Department of Kinesiology, Research Group in Exercise Physiology, KU Leuven, Tervuursevest 101, Box 1500, 3001 Leuven, Belgium.
authors: Louise
authors: L
authors: Deldicque
authors: d Department of Kinesiology, Research Group in Exercise Physiology, KU Leuven, Tervuursevest 101, Box 1500, 3001 Leuven, Belgium.
authors: Monique
authors: M
authors: Ramaekers
authors: d Department of Kinesiology, Research Group in Exercise Physiology, KU Leuven, Tervuursevest 101, Box 1500, 3001 Leuven, Belgium.
authors: Peter
authors: P
authors: Hespel
authors: a Department of Movement and Sport Sciences, Ghent University, Watersportlaan 2, 9000 Ghent, Belgium.
authors: Wim
authors: W
authors: Derave
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002336:Carnosine / Q000008:administration & dosage* / Q000097:blood; D059305:Diet, High-Fat; D019587:Dietary Supplements; D004195:Disease Models, Animal; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015091:beta-Alanine / Q000008:administration & dosage / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D018836:Inflammation Mediators; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D015091:beta-Alanine; D002336:Carnosine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: advanced glycation end products; advanced lipoxidation end products; aptitude à désaltérer; bêta-alanine; carnosine conjugates; conjugués de carnosine; inflammatory signaling; produits finaux de la glycation avancée; produits finaux de la lipoxydation avancée; quenching ability; signalisation de l’inflammation; β-alanine