This study examined the effects of the novel carbonyl scavenger carnosinol on metabolic syndrome in mice fed a high fat, high sucrose diet. Mice lacking an enzyme that neutralizes lipid peroxidation products (LPPs) and normal mice were fed this diet for 16 weeks. Treatment with carnosinol for the second half of the study period improved glucose tolerance by 60% and 22% respectively in the two mouse models and reduced cholesterol levels that were elevated by the high fat diet. The findings suggest that LPPs contribute to metabolic syndrome induced by western diets and that scavenging LPPs with carnosinol has potential to improve metabolic health parameters.

1. The Effect of Novel Carbonyl Scavenger Carnosinol On Metabolic Syndrome in
Mice On Fed a High Fat, High Sucrose Diet.
Hannah E. Mitchell1
, Cherise N. Beatty1
, Lalage A. Katunga1
,Giancarlo Aldini2
Ethan J Anderson1
. 1
Pharmacology & Toxicology, East Carolina University,
Greenville, NC 2
Department of Pharmaceutical Sciences, University of Milan,
Milan, Italy
The aldehydes are lipid peroxidation products (LPPS) generated via the
spontaneous oxidation of polyunsaturated fatty acids (PUFA). To establish the
contribution of LPPs to the metabolic syndrome precipitated by Western dietary
habits male C57BL/6 mice(WT) and Glutathione Peroxidase 4 (GP4X+/-) (n=8)
were placed on a n-6 PUFA enriched high fat high sucrose (HFHS) diet
control(CNTL) diet for 16 weeks. GPX4 is the only enzyme capable of
neutralizing LPPS thus haploinsufficency serves as a model of elevated LPP
production. To determine whether scavenging LPPs can mitigate metabolic
syndrome we treated separate GPX4+/- and WT mice with carnosinol (CAR), a
novel carbonyl scavenging compound. CAR intervention (40mg/kg) began after 8
weeks on the HFHS diet. There was no significant difference in food and water
consumption or body composition (~40% fat) between HFHS fed groups with
CAR treatment. CAR increased glucose tolerance by 60% and 22% in WT and
GPx4+/- respectively. Blood pressure was not significantly different. Cholesterol
levels were ~25% higher in mice on the HFHS diet and were reduced with CAR.
These findings suggest that LPPs maybe important in the etiology of metabolic
syndrome induced by a western style diet and provide evidence that scavenging
LPPs with CAR has potential to improve metabolic parameters.