Peripheral cannabinoid 1 receptor blockade mitigates adipose tissue inflammation via NLRP3 inflammasome in mouse models of obesity.

AIM: To analyze the metabolic parameters and adipose tissue inflammation via NLRP3 inflammasome following chronic treatment of mouse models of obesity with AJ5018 as the peripherally restricted cannabinoid 1 receptor (CB1R) antagonist. MATERIALS AND METHODS: The selectivity for CB1R over CB2R, brain/plasma concentration ratio, and centrally mediated neurobehavioural effects of AJ5018, were assessed. The long-term effects of AJ5018 and rimonabant on the metabolic parameters and adipose tissue inflammation were analyzed in diet-induced obese (DIO) mice and diabetic db/db mice. RESULTS: AJ5018 had a higher degree of selectivity for CB1R over CB2R and markedly reduced brain penetrance, as reflected by the lower brain/plasma concentration ratio and the attenuated centrally mediated neurobehavioural effects, compared with its brain-penetrant parent compound rimonabant. In DIO and db/db mice, AJ5018 exhibited comparable effects to rimonabant in improving metabolic abnormalities and suppressing macrophage infiltration into white adipose tissue, activation of the NLRP3 inflammasome, and production of proinflammatory cytokines. CONCLUSIONS: These results suggest that peripheral CB1R blockade improves obesity-induced insulin resistance by suppressing adipose tissue inflammation via the NLRP3 inflammasome.

Use of vitamins, minerals, and other dietary supplements by 17- and 18-year-old students in Korea.

Various types of dietary supplements (DS) are popularly taken by young individuals. We surveyed 1,190 Korean senior high school third grade students for their DS use, motivational factors for this use, and potential dietary consequences of vitamin/mineral supplement (VMS) use. The use prevalence of DS-including VMS, tonic medicines, manufactured health food supplements, cordial food supplements, and drink rehabilitators-was 54%. VMS were taken most frequently, followed by tonic medicines and manufactured health food supplements. VMS use was highest in individuals who had a significant concern for their overall health and in those from families with a high socioeconomic level and with parental use of DS. Total daily study time of DS users was only slightly longer than that of nonusers. The VMS most frequently used were vitamin C and multivitamins. More than 46% of other DS users, and 58% of VMS users, had increased their intake of supplements during third grade relative to the previous year. VMS users had a more positive view of the potential health benefit of VMS than did nonusers. Vitamin and mineral intakes from VMS occurred over a wide range, with mean intakes typically exceeding the Korean and Canadian-U.S. Recommended Dietary Allowances. For a significant number of individuals, intakes of vitamin A, niacin, folic acid, vitamin C, calcium, iron, and zinc exceeded the Tolerable Upper Intake Levels. Given the widespread use of DS by older teenagers, the contribution of these supplements to their overall health and well-being is a subject that clearly merits additional study.