Anti-glycation properties of Zinc-enriched Spirulina platensis contribute to prevention of metaflammation in a diet-induced obese mouse model

Advanced glycation endproducts (AGEs) exert key pathogenic role in the development of obe-sity and insulin resistance. Thanks to its abundance in bioactive compounds, the microalga Ar-throspira platensis (Spirulina, SP) is proposed as nutritional supplement. Here we investigated the potential anti-glycating properties of SP enriched with zinc (Zn-SP) and the following impact on diet-induced metabolic derangements. Thirty male C57Bl6 mice were fed a standard diet (SD) or a high-fat high-sugar diet (HFHS) for 12 weeks and a subgroup of HFHS mice received 350 mg/kg Zn-SP three times a week. HFHS diet induced obesity, glucose intolerance and increased plasma levels of pro-inflammatory cytokines and transaminases. Zn-SP administration restored glucose homeostasis and reduced hepatic dysfunction and systemic inflammation. In the liver of HFHS mice a robust accumulation of AGEs was detected, paralleled by increased expression of RAGE and depletion of glyoxalase-1, whereas Zn-SP administration efficiently prevented these alterations reducing local pro-inflammatory response. 16S rRNA gene profiling of feces and ileum content revealed altered microbiota composition in HFHS mice compared to both SD and HFHS+Zn-SP groups. Overall, our study demonstrates relevant anti-glycation properties of Zn-SP which contribute to prevent AGEs production and/or stimulate AGEs detoxification, leading to improvement of diet-related dysbiosis and metabolic derangements.