Synthetic small molecule analogues of the immunomodulatory Acanthocheilonema viteae product ES-62 promote metabolic homeostasis during obesity in a mouse model

Publication date: Available online 18 October 2019Source: Molecular and Biochemical ParasitologyAuthor(s): Felicity E. Lumb, Jenny Crowe, James Doonan, Colin J. Suckling, Colin Selman, Margaret M. Harnett, William HarnettAbstractOne of the most rapidly increasing human public health problems is obesity, whose sequelae like type-2 diabetes, represent continuously worsening, life-long conditions. Over the last 15 years, data have begun to emerge from human and more frequently, mouse studies, that support the idea that parasitic worm infection can protect against this condition. We have therefore investigated the potential of two synthetic small molecule analogues (SMAs) of the anti-inflammatory Acanthocheilonema viteae product ES-62, to protect against metabolic dysfunction in a C57BL/6 J mouse model of high calorie-induced obesity. We found weekly subcutaneous administration of the SMAs in combination (1 μg of each), starting one week before continuous exposure to high calorie diet (HCD), decreased fasting glucose levels and reversed the impaired glucose clearance observed in male mice, when measured at approximately 7 and 13 weeks after exposure to HCD. Fasting glucose levels were also improved in male mice fed a HCD for some 38 weeks when given SMA-treatment 13 weeks after the start of HCD, indicating an SMA-therapeutic potential. For the most part, protective effects were not observed in female mice. SMA treatment also conferred protection against each of reduced ...
Source: Molecular and Biochemical Parasitology - Category: Parasitology Source Type: research

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Abstract Since time immemorial, humans have coevolved with a wide variety of parasitic helminths that have contributed to shape their immune system. The recent eradication of helminth infections in modern societies has coincided with a spectacular rise in inflammatory metabolic diseases, such as obesity, nonalcoholic steatohepatitis, and type 2 diabetes. Landmark studies in the emerging field of immunometabolism have highlighted the central role of the immune system in regulating metabolic functions, notably in adipose tissue, liver, and the gut. In this review we discuss how helminths, which are among the stronge...
Source: Trends in Parasitology - Category: Parasitology Authors: Tags: Trends Parasitol Source Type: research
Contributors : Yangyue Ni ; Zhipeng Xu ; Yuxiao Zhu ; Ran Liu ; Fan Zhang ; Min Hou ; Minjun JiSeries Type : Non-coding RNA profiling by arrayOrganism : Mus musculusIt is well recognized that parasitic helminth infections, which afflict more than one billion people globally, correlate with a decreased prevalence of metabolic diseases, including obesity and type 2 diabetes, but the molecular mechanisms involved remain to be determined.  Using microarrays, we quantified the temporal gene expression profiles in the liver of Schistosoma japonicum-infected C57BL/6 mice at 9 weeks post infection with that from uninfected mi...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by array Mus musculus Source Type: research
Alessandro Poggi1*, Roberto Benelli2, Roberta Venè1, Delfina Costa1, Nicoletta Ferrari1, Francesca Tosetti1 and Maria Raffaella Zocchi3 1Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 2Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 3Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract Nonalcoholic steatohepatitis (NASH) is a common liver disease associated with metabolic disorders, including obesity and type 2 diabetes (T2D). Despite its worldwide prevalence, there are no effective drugs for the treatment of NASH. The progression of NASH is mainly accelerated by reactive oxygen species (ROS)-induced lipotoxicity. The transcription factor known as nuclear factor erythroid 2-related factor 2 (Nrf2) is pivotal for the elimination of ROS. Accordingly, activators of Nrf2 have been implicated as promising therapeutic targets for the treatment of NASH. Niclosamide ethanolamine (NEN), a drug a...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
Conclusion Human microbiome is normal flora for humans, which has been proved to be of symbiotic relationship with humans and harmless to humans. If the microbes that breed in the human body become “unhealthy,” it will definitely affect the host's physical condition. People are continuing to explore the pathologic relationship between microorganisms and the human body through high-throughput sequencing technologies and analysis systems. However, it is a pity that their pathogenesis cannot be fully understood as yet. Considering that relying only on conventional experimental methods is time-consuming an...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
This study showed that potential vicious cycles underlying ARDs are quite diverse and unique, triggered by diverse and unique factors that do not usually progress with age, thus casting doubts on the possibility of discovering the single molecular cause of aging and developing the single anti-aging pill. Rather, each disease appears to require an individual approach. However, it still cannot be excluded that some or all of these cycles are triggered by fundamental processes of aging, such as chronic inflammation or accumulation of senescent cells. Nevertheless, experimental data showing clear cause and effect relationships...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we fed flies a high-sucrose diet and observed defects in the phagocytosis of latex beads and B. bassiana spores. The actin cytoskeleton was also disrupted in hemocytes from HSD-fed larvae. Furthermore, HSD induced the differentiation of lamellocytes in the lymph gland and circulating hemolymph, which rarely occurs in healthy bodies, via JNK signaling. In addition, the Toll and JNK pathways were excessively activated in the fat bodies of HSD-fed larvae, and a large number of dead cells were observed. Finally, HSD induced the aberrant activation of the innate immune system, including inflammation. Our results ...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research
CONCLUSIONS: Niclosamide piperazine salt may hold the promise to become an alternative to NEN as a drug lead for the treatment of obesity and T2D. No level of evidence Animal study. PMID: 28780747 [PubMed - as supplied by publisher]
Source: Eating and weight disorders : EWD - Category: Eating Disorders & Weight Management Authors: Tags: Eat Weight Disord Source Type: research
Summary Nutritional immunology, immunometabolism and identification of novel immunotherapeutic targets are areas of active investigation in parasitology. There is a well‐documented crosstalk among immune cells and cells in metabolically active tissues that is important for homeostasis. The numbers and function of these cells are altered by obesity leading to inflammation. A variety of helminths spend some part of their life cycle in the gastrointestinal tract and even entirely enteral nematode infections exert beneficial effects on glucose and lipid metabolism. The foundation of this review is the ability of enteric nema...
Source: Parasite Immunology - Category: Parasitology Authors: Tags: COMMISSIONED REVIEW ARTICLE Source Type: research
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Source: Parasite Immunology - Category: Parasitology Authors: Tags: Commissioned Review or Article Source Type: research
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