Regulation of host metabolic health by parasitic helminths.

Obesity is a worldwide pandemic and major risk factor for the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). T2D requires lifelong medical support to limit complications and is defined by impaired glucose tolerance, insulin resistance (IR), and chronic low-level systemic inflammation initiating from adipose tissue. The current preventative strategies include a healthy diet, controlled physical activity, and medication targeting hyperglycemia, with underexplored underlying inflammation. Studies suggest a protective role for helminth infection in the prevention of T2D. The mechanisms may involve induction of modified type 2 and regulatory immune responses that suppress inflammation and promote insulin sensitivity. In this review, the roles of helminths in counteracting MetS, and prospects for harnessing these protective mechanisms for the development of novel anti-diabetes drugs are discussed.

Association between Toxoplasma gondii infection and metabolic syndrome in obese adolescents: A possible immune-metabolic link.

Background Toxoplasmosis as a global disease is considered as a triggering factor responsible for development of several clinical diseases. However, Toxoplasma gondii (T. gondii) is an understudied parasite of potential interest in obesity research. The current study aimed to explore the role of latent T. gondii infection in the pathogenesis of metabolic syndrome (MetS) in obese adolescents through studying the relationship between serum interferon-gamma [IFN-γ] and serum chemerin in context of MetS components. Methods Eighty-three obese adolescents were serologically screened for T. gondii-IgG antibodies and compared to 35 age-matched healthy T. gondii-seronegative controls. Participants were evaluated for anthropometric measurements, total-fat mass [FM], trunk-FM, serum lipid profile, IFN-γ, and chemerin levels. Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Results The prevalence of MetS was significantly higher within obese T. gondii-seropositive group compared to obese T. gondii-seronegative group (P = 0.033). Seropositive obese MetS group displayed significantly higher trunk-FM, HOMA-IR, chemerin, and IFN-γ compared to seronegative obese MetS group. Serum chemerin and IFN-γ were strongly correlated (P < 0.001) and were positively correlated with BMI, WC, total-FM, trunk-FM, HOMA-IR, cholesterol, triglycerides and negatively correlated with HDLC. HOMA-IR was a common predictor for serum chemerin (P = 0.030) and IFN-γ (P < 0.001). Conclusions The study results suggest that T. gondii infection may exert an immune-metabolic effect that may have a potential role in the development of MetS among obese adolescents.

Do worms protect against the metabolic syndrome? A systematic review and meta-analysis.

AIMS: There is increasing evidence on the role of helminth infections in modifying autoimmune and allergic diseases. These infections may have similar effect in other inflammatory processes, such as insulin resistance. This review aims to examine the literature on the effect of helminthic infections on metabolic outcomes in humans. METHODS: Using the PRISMA protocol, we searched the literature using PubMed, MEDLINE, and a manual review of reference lists. Human studies published in English after 1995 were included. Four papers were included in this review. Data was extracted and a meta-analysis was conducted using a random-effects model. Heterogeneity was assessed using Tau(2) and I(2) tests. RESULTS: The included studies found that infection was associated with lower glucose levels, less insulin resistance, and/or a lower prevalence of metabolic syndrome (MetS) or type 2 diabetes mellitus (T2DM). Meta-analysis showed that participants with a previous or current helminth infection were 50% less likely to have an endpoint of metabolic dysfunction in comparison to uninfected participants (OR 0.50; 95% CI 0.38-0.66). CONCLUSION: This review has shown that helminth infections can be associated with improved metabolic outcomes. Understanding of the mechanisms underlying this relationship could facilitate the development of novel strategies to prevent or delay T2DM.

Diabetes tipo 2 y síndrome metabólico, utilidad del índice triglicéridos/HDL colesterol en Pediatría / Type 2 diabetes mellitus and the metabolic syndrome, usefulness of the triglyceride/HDL cholesterol indexes in pediatrics

Introducción: se estima que la diabetes mellitus tipo 2 en la edad pediátrica, representa el 2-3 por ciento de todos los casos; sin embargo, en los últimos años ha mostrado un incremento de 10 veces. Objetivos: describir los elementos clave que permitan realizar una detección precoz desde la infancia, y destacar la importancia del índice triglicéridos/HDL colesterol como indicador de riesgo metabólico e insulinorresistencia, para lo cual se revisaron las bases de datos Medline/Pub-Med, SciELO, BVS España, la Sociedad Iberoamericana de Información Científica, Ediciones DOYMA y Elsevier, de los últimos 10 años (desde junio de 2005 a junio 2015) en inglés y en español. Desarrollo: la diabetes mellitus tipo 2 es el resultado de la interacción de factores genéticos y ambientales. El síndrome metabólico es una agrupación de factores de riesgo cardiovascular y de diabetes tipo 2. Se recomienda incorporar nuevas variables como el cociente triglicéridos/HDL colesterol para implementar estrategias preventivas. Consideraciones finales: se deben hacer pesquisas activas en las poblaciones de riesgo. La elevación del índice triglicéridos/HDL colesterol se relaciona con la insulinorresistencia y resulta de fácil aplicación(AU)

Introduction: it is estimated that type 2 diabetes mellitus accounts for 2-3 percent of all cases at pediatric ages; however, there has been a 10-fold increase of the number of patients in the last few years. Objectives: to describe the key elements for early detection of diabetes in childhood and to stress the importance of the triglyceride/HDL cholesterol ratio as a sign of metabolic risk and insulin resistance. To this end, Medline/PubMed, SciELO, BVS Spain, the Ibero-American Society of Scientific Information, DOYMA and Elsevier Editions databases in the last ten years were reviewed (June 2005 to June 2015) in English and Spanish. Development: type 2 diabetes mellitus is the result of genetic and environmental risk factors. The metabolic syndrome is a grouping of cardiovascular and type 2 risk factors. It is then recommended to add new variables such as triglyceride/HDL cholesterol ratio to implement preventive strategies. Final thoughts: active screening should be performed in risk populations. High triglyceride/HDL cholesterol ratio is related to insulin resistance and the application of this indicator is easy(AU)

A worm of one's own: how helminths modulate host adipose tissue function and metabolism.

Parasitic helminths have coexisted with human beings throughout time. Success in eradicating helminths has limited helminth-induced morbidity and mortality but is also correlated with increasing rates of 'western' diseases, including metabolic syndrome and type 2 diabetes. Recent studies in mice describe how type 2 immune cells, traditionally associated with helminth infection, maintain adipose tissue homeostasis and promote adipose tissue beiging, protecting against obesity and metabolic dysfunction. Here, we review these studies and discuss how helminths and helminth-derived molecules may modulate these physiologic pathways to improve metabolic functions in specific tissues, such as adipose and liver, as well as at the whole-organism level.

The brighter (and evolutionarily older) face of the metabolic syndrome: evidence from Trypanosoma cruzi infection in CD-1 mice.

BACKGROUND: Infection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high-fat diet (HFD) protected mice from T. cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T. cruzi infection. METHODS: In the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin. RESULTS: In the present study, the lethality of T. cruzi (Brazil strain) infection in CD-1 mice was reduced from 55% to 20% by an 8-week pre-feeding of an HFD to induce obesity and metabolic syndrome. The addition of metformin reduced mortality to 3%. CONCLUSIONS: It is an interesting observation that both the high fat diet and the metformin, which are known to differentially attenuate host metabolism, effectively modified mortality in T. cruzi-infected mice. In humans, the metabolic syndrome, as presently construed, produces immune activation and metabolic alterations that promote complications of obesity and diseases of later life, such as myocardial infarction, stroke, diabetes, Alzheimer's disease and cancer. Using an evolutionary approach, we hypothesized that for millions of years, the channeling of host resources into immune defences starting early in life ameliorated the effects of infectious diseases, especially chronic infections, such as tuberculosis and Chagas disease. In economically developed countries in recent times, with control of the common devastating infections, epidemic obesity and lengthening of lifespan, the dwindling benefits of the immune activation in the first half of life have been overshadowed by the explosion of the syndrome's negative effects in later life.

Chagas disease, adipose tissue and the metabolic syndrome.

Trypanosoma cruzi infection of the adipose tissue of mice triggers the local expression of inflammatory mediators and a reduction in the expression of the adipokine adiponectin. T. cruzi can be detected in adipose tissue by PCR 300 days post-infection. Infection of cultured adipocytes results in increased expression of cytokines and chemokines and a reduction in the expression of adiponectin and the peroxisome proliferator-activated receptor gamma, both of which are negative regulators of inflammation. Infection also results in the upregulation of cyclin D1, the Notch pathway, and extracellular signal-regulated kinase and a reduction in the expression of caveolin-1. Thus, T. cruzi infection of cultured adipocytes leads to an upregulation of the inflammatory process. Since adiponectin null mice have a cardiomyopathic phenotype, it is possible that the reduction in adiponectin contributes to the pathogenesis of chagasic cardiomyopathy. Adipose tissue may serve as a reservoir for T. cruzi from which parasites can become reactivated during periods of immunosuppression. T. cruzi infection of mice often results in hypoglycemia. In contrast, hyperglycemia as observed in diabetes results in increased parasitemia and mortality. Adipose tissue is an important target tissue of T. cruzi and the infection of this tissue is associated with a profound impact on systemic metabolism, increasing the risk of metabolic syndrome.

Chagas disease, adipose tissue and the metabolic syndrome

Trypanosoma cruzi infection of the adipose tissue of mice triggers the local expression of inflammatory mediators and a reduction in the expression of the adipokine adiponectin. T. cruzi can be detected in adipose tissue by PCR 300 days post-infection. Infection of cultured adipocytes results in increased expression of cytokines and chemokines and a reduction in the expression of adiponectin and the peroxisome proliferator-activated receptor ³, both of which are negative regulators of inflammation. Infection also results in the upregulation of cyclin D1, the Notch pathway, and extracellular signal-regulated kinase and a reduction in the expression of caveolin-1. Thus, T. cruzi infection of cultured adipocytes leads to an upregulation of the inflammatory process. Since adiponectin null mice have a cardiomyopathic phenotype, it is possible that the reduction in adiponectin contributes to the pathogenesis of chagasic cardiomyopathy. Adipose tissue may serve as a reservoir for T. cruzi from which parasites can become reactivated during periods of immunosuppression. T. cruzi infection of mice often results in hypoglycemia. In contrast, hyperglycemia as observed in diabetes results in increased parasitemia and mortality. Adipose tissue is an important target tissue of T. cruzi and the infection of this tissue is associated with a profound impact on systemic metabolism, increasing the risk of metabolic syndrome.

Metabolic syndrome and obesity in an insect.

Dragonflies infected with noninvasive gregarine gut parasites (Apicomplexa: Eugregarinorida) [corrected] have reduced flight-muscle performance, an inability to metabolize lipid in their muscles, twofold-elevated hemolymph carbohydrate concentrations, and they accumulate fat in their thorax in a manner analogous to mammalian obesity. Gregarine infection is associated with inappropriate responses of hemolymph carbohydrate concentration to insulin and with chronic activation in the flight muscles of p38 MAP kinase, a signaling molecule involved in immune and stress responses. Short-term exposure to gregarine excretory/secretory products caused elevated blood carbohydrate and p38 MAPK activation in healthy individuals. These characteristics comprise a set of symptoms and processes that are known in mammals as metabolic syndrome but which have not previously been described in other animal taxa. In addition to expanding the known taxonomic breadth of metabolic disease, these results indicate that insects may be useful experimental models for studying its underlying biology and mechanisms.