lactoferrin and Metabolic-Syndrome

Many pathological conditions, including obesity, diabetes, hypertension, heart disease, and cancer, are associated with abnormal metabolic states. The progressive loss of metabolic control is commonly characterized by insulin resistance, atherogenic dyslipidemia, inflammation, central obesity, and hypertension, a cluster of metabolic dysregulations usually referred to as the "metabolic syndrome". Recently, nutraceuticals have gained attention for the generalized perception that natural substances may be synonymous with health and balance, thus becoming favorable candidates for the adjuvant treatment of metabolic dysregulations. Among nutraceutical proteins, lactoferrin (Lf), an iron-binding glycoprotein of the innate immune system, has been widely recognized for its multifaceted activities and high tolerance. As this review shows, Lf can exert a dual role in human metabolism, either boosting or resetting it under physiological and pathological conditions, respectively. Lf consumption is safe and is associated with several benefits for human health, including the promotion of oral and gastrointestinal homeostasis, control of glucose and lipid metabolism, reduction of systemic inflammation, and regulation of iron absorption and balance. Overall, Lf can be recommended as a promising natural, completely non-toxic adjuvant for application as a long-term prophylaxis in the therapy for metabolic disorders, such as insulin resistance/type II diabetes and the metabolic syndrome.

Topics: Adjuvants, Immunologic; Diabetes Mellitus, Type 2; Energy Metabolism; Humans; Hypertension; Inflammation; Insulin Resistance; Iron; Lactoferrin; Metabolic Syndrome; Obesity

Obesity, dyslipidemia, hyperglycemia/type II diabetes and hypertension together constitute the so-called metabolic syndrome. Frequency of occurrence of these serious metabolic disturbances is associated with life style and is on the rise in prosperous industrialized countries. These diseases represent not only a serious health problem but also social and economic ones, and involve in prophylaxis and treatment various specialists (physicians, dieticians and psychologists). For about two decades research has been conducted on the possibility to apply milk-derived proteins in prevention and treatment of the above mentioned metabolic diseases. Lactoferrin (LF), a protein present in milk and excretory fluids of mammals, is one of the most intensively studied milk proteins for therapeutic application. Initial trials revealing an advantageous effect of LF on lipid metabolism and obesity enrolled only a few volunteers and were performed in Japan in 2003. Subsequent trials were conducted on animals as well as in clinics, and the positive results were supported by in vitro tests. After oral administration of LF, decreases of body weight, waist measurement, visceral fat tissue, plasma and liver fatty acid concentrations, triglycerides and cholesterol were registered. The mechanism of LF action may involve several processes, such as inhibition of adipogenesis, decrease of dietary triglyceride absorption, elevation of HDL cholesterol possessing anti-atherogenic properties, inhibition of accumulation of oxidized LDL cholesterol forms in macrophages and protection against formation of foam cells. LF also increases the susceptibility of cells to insulin action, including in conditions when the response to insulin is lowered (during inflammation). In addition, LF regulates activity of insulin-like growth factor (IGF). The data collected to date indicate that LF is a promising, completely nontoxic, natural remedy which (as for example a food supplement) may be applied in long-term prophylaxis and therapy of metabolic disturbances, such as dyslipidemia, obesity and insulin resistance/type II diabetes. 

Topics: Animals; Blood Glucose; Cholesterol, HDL; Humans; Hyperglycemia; Insulin Resistance; Japan; Lactoferrin; Lipid Metabolism; Metabolic Syndrome; Obesity; Somatomedins; Triglycerides

To investigate whether C-reactive protein (CRP, a general marker of inflammation), neopterin (activated macrophages), lactoferrin (activated neutrophils), and endothelial function (flow-mediated vasodilation [FMD]) are associated with cardiorespiratory fitness (peak oxygen uptake [VO. This was a cross-sectional association study based on the population-based HUNT3 Fitness Study performed from May 15, 2007, through June 23, 2008. Seven hundred forty self-reported healthy respondents (327 women) identified as having the MetSyn were age- and sex-matched with 692 controls (307 women) from the same cohort. Associations between the inflammatory biomarkers and VO. The CRP level was negatively associated with VO. The CRP level was strongly associated with VO

Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Cardiorespiratory Fitness; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Female; Humans; Inflammation; Lactoferrin; Male; Metabolic Syndrome; Middle Aged; Neopterin; Oxygen Consumption; Sex Distribution

BackgroundLactoferrin (LTF) could play a beneficial role in insulin resistance and diabetes, but the association of its gene variants with cardio-metabolic disorders in children has not been investigated. This study aimed to examine the relationship between LTF variants, plasma LTF concentrations, and cardio-metabolic risk factors in French-Canadian children.MethodsThe study cohort comprises 1,749 French Canadians aged 9, 13, and 16 years. The association of 13 LTF polymorphisms, metabolic parameters, and plasma LTF levels was tested in this cross-sectional, province-wide school-based survey.ResultsNone of the genetic association remained significant after correction for multiple testing and LTF SNPs were not associated with LTF levels. Plasma LTF was positively correlated with body mass index (r

Topics: Adolescent; Age Factors; Body Mass Index; Body Weight; Child; Cross-Sectional Studies; Female; Genetic Predisposition to Disease; Haplotypes; Health Surveys; Humans; Lactoferrin; Lipids; Male; Metabolic Syndrome; Phenotype; Polymorphism, Single Nucleotide; Quebec; Risk Factors; Sex Factors

Hepatic manifestations of the metabolic syndrome are related obesity, type 2 diabetes/insulin resistance and non-alcoholic fatty liver disease. Here we investigated how the anti-inflammatory properties of lactoferrin can protect against the onset of hepatic manifestations of the metabolic syndrome by using a murine model administered with high-fructose corn syrup. Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver. Immunohistochemical staining of Toll-like receptor-4 and thymic stromal lymphopoietin indicated that lactoferrin can modulate lipopolysaccharide-mediated inflammatory cascade. The important regulatory roles are played by adipokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release. These beneficial effects of lactoferrin related to the downregulation of the lipopolysaccharide-induced inflammatory cascade in the liver. Furthermore, lactoferrin reduced serum and hepatic triglycerides to prevent lipid accumulation in the liver, and reduced lipid peroxidation, resulting in 4-hydroxynonenal accumulation. Lactoferrin reduced oral glucose tolerance test and homeostasis model assessment-insulin resistance. Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis. Taken together, these results suggest that lactoferrin protected against high-fructose corn syrup induced hepatic manifestations of the metabolic syndrome.

Topics: Adipokines; Alanine Transaminase; Analysis of Variance; Animals; Cytokines; Enzyme-Linked Immunosorbent Assay; Glucose Tolerance Test; High Fructose Corn Syrup; Immunohistochemistry; Insulin Resistance; Lactoferrin; Lipopolysaccharides; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Thymic Stromal Lymphopoietin; Toll-Like Receptor 4; Triglycerides