Biological functions of histidine-dipeptides and metabolic syndrome.

Abstract

The rapid increase in the prevalence of metabolic syndrome, which is associated

with a state of elevated systemic oxidative stress and inflammation, is expected

to cause future increases in the prevalence of diabetes and cardiovascular

diseases. Oxidation of polyunsaturated fatty acids and sugars produces reactive

carbonyl species, which, due to their electrophilic nature, react with the

nucleophilic sites of certain amino acids. This leads to formation of protein

adducts such as advanced glycoxidation/lipoxidation end products (AGEs/ALEs),

resulting in cellular dysfunction. Therefore, an effective reactive carbonyl

species and AGEs/ALEs sequestering agent may be able to prevent such cellular

dysfunction. There is accumulating evidence that histidine containing dipeptides

such as carnosine (beta-alanyl-L-histidine) and anserine

(beta-alanyl-methyl-L-histidine) detoxify cytotoxic reactive carbonyls by forming

unreactive adducts and are able to reverse glycated protein. In this review, 1)

reaction mechanism of oxidative stress and certain chronic diseases, 2)

interrelation between oxidative stress and inflammation, 3) effective reactive

carbonyl species and AGEs/ALEs sequestering actions of histidine-dipeptides and

their metabolism, 4) effects of carnosinase encoding gene on the effectiveness of

histidine-dipeptides, and 5) protective effects of histidine-dipeptides against

progression of metabolic syndrome are discussed. Overall, this review highlights

the potential beneficial effects of histidine-dipeptides against metabolic

syndrome. Randomized controlled human studies may provide essential information

regarding whether histidine-dipeptides attenuate metabolic syndrome in humans.