Zinc deficiency exacerbates while zinc supplement attenuates cardiac hypertrophy in high-fat diet-induced obese mice through modulating p38 MAPK-dependent signaling.

Childhood obesity often leads to cardiovascular diseases, such as obesity-related cardiac hypertrophy (ORCH), in adulthood, due to chronic cardiac inflammation. Zinc is structurally and functionally essential for many transcription factors; however, its role in ORCH and underlying mechanism(s) remain unclear and were explored here in mice with obesity induced with high-fat diet (HFD). Four week old mice were fed on either HFD (60%kcal fat) or normal diet (ND, 10% kcal fat) for 3 or 6 months, respectively. Either diet contained one of three different zinc quantities: deficiency (ZD, 10mg zinc per 4057kcal), normal (ZN, 30mg zinc per 4057kcal) or supplement (ZS, 90mg zinc per 4057kcal). HFD induced a time-dependent obesity and ORCH, which was accompanied by increased cardiac inflammation and p38 MAPK activation. These effects were worsened by ZD in HFD/ZD mice and attenuated by ZS in HFD/ZS group, respectively. Also, administration of a p38 MAPK specific inhibitor in HFD mice for 3 months did not affect HFD-induced obesity, but completely abolished HFD-induced, and zinc deficiency-worsened, ORCH and cardiac inflammation. In vitro exposure of adult cardiomyocytes to palmitate induced cell hypertrophy accompanied by increased p38 MAPK activation, which was heightened by zinc depletion with its chelator TPEN. Inhibition of p38 MAPK with its specific siRNA also prevented the effects of palmitate on cardiomyocytes. These findings demonstrate that ZS alleviates but ZD heightens cardiac hypertrophy in HFD-induced obese mice through suppressing p38 MAPK-dependent cardiac inflammatory and hypertrophic pathways.

Zinc delays the progression of obesity-related glomerulopathy in mice via down-regulating P38 MAPK-mediated inflammation.

OBJECTIVE: Obesity, particularly child obesity, is one of the most common public health problems in the world and raises the risk of end-stage renal disease. Zinc (Zn) is essential for multiple organs in terms of normal structure and function; however, effects of Zn deficiency or supplementation among young individuals with obesity have not been well studied. METHODS: Weaned mice were fed high-fat diets (HFD) with varied contents of Zn (Zn deficient, adequate, and supplemented) for 3 or 6 months. This study examined associations between renal pathogenesis and dietary Zn levels, specifically assessing inflammatory pathways by utilizing P38 MAPK inhibitor SB203580. RESULTS: HFD feeding induced typical syndromes of obesity-related renal disorders, which worsened by Zn marginal deficiency. The progression of obesity-related renal disorders was delayed by Zn supplementation. HFD induced renal inflammation, reflected by increased P38 MAPK phosphorylation along with increases of inflammatory cytokines MCP-1, IL-1ß, IL-6, and TNF-α. P38 MAPK inhibition prevented renal pathological changes in mice fed with HFD and HFD/Zn deficiency. CONCLUSIONS: P38 MAPK mediated the renal inflammatory responses, which played a central role in the pathogenesis of HFD-induced renal disorders. Zn could delay the progression of obesity-related kidney disease by down-regulating P38 MAPK-mediated inflammation.

Vitamins and sleep: an exploratory study.

STUDY OBJECTIVE: We analyzed archival data from an epidemiology study to test the association between vitamin use and sleep. DESIGN: Random digit dialing was used to recruit 772 people ranging in age from 20 to 98 for a study of people's sleep experience. These individuals completed a set of questionnaires about their sleep, health, and daytime functioning. Five hundred and nineteen of these participants had available vitamin use data. SETTING: Home. PARTICIPANTS: Five hundred and nineteen people participated. Recruitment applied minimal screening criteria and no attempt was made to favor people with or without sleep disturbance. INTERVENTIONS: This survey included no intervention. Participants completed 2 weeks of sleep diaries and a set of questionnaires. Of particular salience to the present study, participants reported their vitamin use in listing all medications and nutritional supplements being used currently. MEASUREMENTS AND RESULTS: For those individuals taking a multivitamin or multiple single vitamins, sleep diaries revealed poorer sleep compared to non-vitamin users in the number and duration of awakenings during the night. After controlling for age, ethnicity, and sex the difference in number of awakenings was still marginally significant. The rate of insomnia, conservatively defined, and consumption of sleep medication were also marginally significantly higher among individuals taking multi-/multiple vitamins compared to those not taking vitamins. CONCLUSIONS: Disturbed sleep maintenance was associated with multi-/multiple vitamin use. Five equally plausible explanations were advanced to explain this association including vitamins cause poor sleep, poor sleepers seek vitamins, and unidentified factors promote both poor sleep and vitamin use. These data are considered preliminary. Methodological characteristics of future studies were described that hold the promise of more clearly illuminating the association between vitamins and sleep.