Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress

Appl Physiol Nutr Metab. 2015 Sep;40(9):868-76. doi: 10.1139/apnm-2015-0042.


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.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / blood
  • Blood Glucose / metabolism
  • Carnosine / administration & dosage*
  • Carnosine / blood
  • Diet, High-Fat*
  • Dietary Supplements*
  • Disease Models, Animal
  • Inflammation / blood
  • Inflammation / etiology
  • Inflammation / genetics
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism
  • Insulin / blood
  • Insulin Resistance
  • Lipid Peroxidation / drug effects*
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • beta-Alanine / administration & dosage
  • beta-Alanine / blood


  • Anti-Inflammatory Agents
  • Blood Glucose
  • Inflammation Mediators
  • Insulin
  • Tumor Necrosis Factor-alpha
  • beta-Alanine
  • Carnosine
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat