leptin and Malaria

The provision of iron- fortified foods is a common strategy to prevent iron deficiency; however, ensuring adequate iron absorption is a challenge. Iron bioavailability depends on the choice of iron compound, the presence enhancers and inhibitors of absorption in the food matrix, and the physiological state of the consumer, including iron status, other nutritional deficiencies and inflammatory disorders. Inflammation associated with infections and inflammatory disorders would be expected to decrease iron absorption and reduce the efficacy of iron- fortified foods. The decreased absorption is due to an increase in circulating hepcidin in response to inflammatory cytokines. Hepcidin degrades ferroportin and blocks the passage of iron from the intestinal cell to the plasma. This is the innate immune response to infections and aims to restrict pathogen growth by restricting iron supply. Stable isotope studies have reported women and children with chronic malaria parasitemia or febrile malaria to have increased inflammatory cytokines, increased hepcidin and much decreased iron absorption. No studies have specifically investigated the efficacy of iron- fortified foods in the absence and presence of infections. In contrast, inflammation and increased hepcidin associated with adiposity in overweight have been linked to both lower iron absorption and the decreased efficacy of iron- fortified foods.

Topics: Adiposity; Biological Availability; Food, Fortified; Hepcidins; Humans; Inflammation; Intestinal Absorption; Iron, Dietary; Leptin; Malaria; Nutritional Status

Topics: Animals; Comorbidity; Diabetes Mellitus; Global Health; HIV Infections; Humans; Infections; Leptin; Malaria; Malnutrition; Measles; Obesity; Protein-Energy Malnutrition; Risk Factors; T-Lymphocytes; Tuberculosis

To investigate the effect of leptin transgenic Plasmodium yoelii on mouse body weight.. To construct the leptin gene-containing CRISPR/Cas9 recombinant plasmid which had the 5′UTR and 3′UTR of MIF(macrophage migration inhibitory factor) of Plasmodium yoelli 17XNL strain at two ends, the exogenous mouse leptin gene was inserted downstream of MIF coding region through homologous recombination, resulting in the PYC-MIF-Leptin recombinant plasmid. The recombinant plasmid was then electroporated into P. y 17XNL mature schizonts, and the transgenic schizonts were used to infect a Kunming mouse via tail vein injection. The trangenic P. y clone was screened by pyrimethamine selection and identified by PCR. The trangenic or wild-type P. y was used to infect a C57BL/6 mouse respectively. Blood sample was collected through eye ball and tail vein, and immunofluorescence and RT-PCR were performed to determine the expression of leptin protein in the parasites. Finally, PBS (200 μl) containing trangenic or wild-type P. y (1 × 104) was injected through the tail vein into C57BL/6 mice(n = 5 respectively). The negative control received a same volume of PBS. The changes of parasitemia and body weight were recorded every two days.. The leptin-expressing recombinant plasmid PYC-MIF-Leptin was constructed successfully. Results of DNA sequencing of transgenic parasites confirmed the integration of leptin gene at the downstream of MIF gene and successful transcription. Immunofluorescence results indicated successful expression of mouse leptin protein. The weight loss was significant in mice infected with transgenic parasites on day 17(17.26 ± 1.40)g, decreased by 10.7%, but not in the other two groups. Both transgenic and wild-type parasites began to decline when parasitemia reached about 10%, but the transgenic parasites proliferated more rapidly. Both disappeared at 23 days.. Infection with leptin transgenic parasites decreases the body weight of the infected mice.

Topics: Animals; Body Weight; Leptin; Malaria; Mice; Mice, Inbred C57BL; Mice, Transgenic; Parasitemia; Plasmodium yoelii

To investigate effects of falciparum malaria on circulating levels of leptin and adiponectin in type 2 diabetes mellitus (T2DM) and non-diabetic controls in relation to measures of adiposity.. Levels of leptin and adiponectin were measured in 100 type 2 diabetics and 100 age-matched controls before and during falciparum malaria in a 2-year prospective study. Also, waist circumference (WC), weight, height and hip circumference were measured. Body mass index (BMI) and waist-to-hip ratio (WHR) were computed.. At baseline, diabetics had significantly (p < 0.05) higher WC and BMI but lower WHR, leptin and adiponectin levels. Baseline leptin correlated positively with WC (r = 0.633; p < 0.001) and BMI (r = 0.63; p < 0.001) in diabetics but only BMI (0.562; p < 0.001) in non-diabetic controls. Baseline leptin and adiponectin correlated positively (r = 0.249; p = 0.029) in non-diabetic respondents only. Adiponectin correlated negatively with WC (r = -0.58; p = 0.006) in diabetic males only. During malaria, mean levels of leptin and adiponectin were comparable (p > 0.05) between diabetics and controls. However, compared to baseline levels, significant (p < 0.001) elevation of adiponectin was found in both study groups. In respect of leptin, significant (p < 0.001) rise but decline was observed in diabetics and controls respectively. Malaria-induced leptin correlated negatively with adiponectin (r = -0.694; p < 0.001) in non-diabetic controls only.. Diabetics and controls exhibited increased adiponectin levels due to falciparum malaria but differed in response in terms of leptin levels.

Topics: Adiponectin; Diabetes Mellitus, Type 2; Humans; Leptin; Malaria; Prospective Studies

Topics: Acquired Immunodeficiency Syndrome; Animal Rights; Compassionate Use Trials; Coronary Artery Bypass; Dietary Sucrose; Drug and Narcotic Control; Drug Carriers; Drug Industry; Global Health; Health Policy; Humans; Leptin; Lipodystrophy; Malaria; Nonprescription Drugs; Tuberculosis; World Health Organization

Inflammation during placental malaria (PM) is associated with low birth weight (LBW), especially during the first pregnancy, but the relative contribution of maternal or fetal factors that mediate this effect remains unclear and the role of gamma interferon (IFN-gamma) has been controversial. We examined the relationship of maternal and cord plasma levels of IFN-gamma, tumor necrosis factor alpha, interleukin-10, ferritin, and leptin to birth weight for Tanzanian women delivering in an area where there is a high rate of malaria transmission. The placental levels of inflammatory cytokines, including IFN-gamma, increased significantly during PM in primigravid and multigravid women but not in secundigravid women. PM also increased maternal peripheral levels of all inflammatory markers except IFN-gamma but had strikingly little effect on cord levels of these proteins. In a multivariate analysis, placental IFN-gamma was negatively associated (P = 0.01) and cord ferritin was positively associated (P < 0.0001) with birth weight in infected (PM-positive [PM+]) first-time mothers. This relationship was not observed in other mothers, consistent with the epidemiology of PM and disease. Cord leptin had a strong positive relationship with birth weight in offspring of PM-negative women (P = 0.02 to P < 0.0001) but not in offspring of PM+ women (all differences were not significant) in the three gravidity groups. The results confirmed that placental IFN-gamma is related to LBW due to PM during first pregnancies and suggest that fetal ferritin plays a protective role. Because fetal cells are a source of placental IFN-gamma and cord ferritin, the fetal response to PM may modify the risk of LBW.

Topics: Adolescent; Adult; Cohort Studies; Cytokines; Female; Ferritins; Fetal Blood; Fetus; Humans; Infant, Low Birth Weight; Infant, Newborn; Leptin; Malaria; Male; Middle Aged; Placenta; Pregnancy; Pregnancy Complications, Parasitic; Risk Factors

Leptin, which is involved in a range of physiological processes, could be an important factor in the pathogenesis of malaria. We found that levels of leptin in serum and urine in Plasmodium berghei-infected mice increased progressively after infection, reaching a maximum value on day 6 post-infection. Serum values were approximately five-fold higher in infected mice than in non-infected controls. A similar relation was found for values of leptin in urine. Soluble leptin receptor levels also increased significantly in serum, more or less in line with the leptin increase. Our work represents the first report of visibly augmented leptin and soluble leptin receptor secretion in malarial infection.

Topics: Animals; Enzyme-Linked Immunosorbent Assay; Leptin; Malaria; Male; Mice; Mice, Inbred C57BL; Plasmodium berghei; Receptors, Cell Surface; Receptors, Leptin