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

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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.
Keywords
SUPPLEMENTATION, HISTIDINE, NULL MICE, DOUBLE-BLIND, DIABETIC-RATS, CARBONYL STRESS, SKELETAL-MUSCLE, BETA-ALANINE, INSULIN-RESISTANCE, GLYCATION END-PRODUCTS, carnosine conjugates, β-alanine, inflammatory signaling, quenching ability, advanced lipoxidation end products, advanced glycation end products

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Chicago
Stegen, Sanne, Bart Stegen, Giancarlo Aldini, Alessandra Altomare, Luca Cannizzaro, Marica Orioli, Sarah Gerlo, et al. 2015. “Plasma Carnosine, but Not Muscle Carnosine, Attenuates High-fat Diet-induced Metabolic Stress.” Applied Physiology Nutrition and Metabolism 40 (9): 868–876.
APA
Stegen, S., Stegen, B., Aldini, G., Altomare, A., Cannizzaro, L., Orioli, M., Gerlo, S., et al. (2015). Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress. APPLIED PHYSIOLOGY NUTRITION AND METABOLISM, 40(9), 868–876.
Vancouver
1.
Stegen S, Stegen B, Aldini G, Altomare A, Cannizzaro L, Orioli M, et al. Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress. APPLIED PHYSIOLOGY NUTRITION AND METABOLISM. 2015;40(9):868–76.
MLA
Stegen, Sanne, Bart Stegen, Giancarlo Aldini, et al. “Plasma Carnosine, but Not Muscle Carnosine, Attenuates High-fat Diet-induced Metabolic Stress.” APPLIED PHYSIOLOGY NUTRITION AND METABOLISM 40.9 (2015): 868–876. Print.
@article{7082750,
  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 \ensuremath{\beta}-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\% \ensuremath{\beta}-alanine (HFba), as \ensuremath{\beta}-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(\ensuremath{\epsilon})-(carboxymethyl)lysine in HF rats was reduced by \ensuremath{\sim}50\% in the HFcar group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA was decreased by 47\% (p {\textlangle} 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.},
  author       = {Stegen, Sanne and Stegen, Bart and Aldini, Giancarlo and Altomare, Alessandra and Cannizzaro, Luca and Orioli, Marica and Gerlo, Sarah and Deldicque, Louise and Ramaekers, Monique and Hespel, Peter and Derave, Wim},
  issn         = {1715-5312},
  journal      = {APPLIED PHYSIOLOGY NUTRITION AND METABOLISM},
  language     = {eng},
  number       = {9},
  pages        = {868--876},
  title        = {Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress},
  url          = {http://dx.doi.org/10.1139/apnm-2015-0042},
  volume       = {40},
  year         = {2015},
}

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