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

Guigas, Bruno; Molofsky, Ari B.

doi:10.1016/j.pt.2015.04.008

Cited by 39 publications

(28 citation statements)

References 92 publications

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“…Helminth parasites-dependent host responses induce alternative macrophage activation and impact the whole body metabolism (Guigas and Molofsky 2015). Therefore, we next performed an ipITT on uninfected control and infected control and MIKO mice.…”

Section: Resultsmentioning

confidence: 99%

IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge

et al. 2017

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SUMMARY In concert with their phagocytic activity, macrophages are thought to regulate the host immunometabolic responses primarily via their ability to produce specific cytokines and metabolites. Here we show that IL-4 differentiated M2-like macrophages secrete IGF1, a hormone previously thought to be exclusively produced from liver. Ablation of IGF1 receptor from myeloid cells reduced phagocytosis, increased macrophages in adipose tissue, elevated adiposity, lowered energy expenditure and led to insulin-resistance in mice fed high fat diet. The investigation of adipose macrophage phenotype in obese myeloid IGF1R knock out (MIKO) revealed a reduction in transcripts associated with M2-like macrophage activation. Furthermore, the MIKO mice infected with helminth Nippostrongylus brasiliensis displayed delayed resolution from infection with normal insulin-sensitivity. Surprisingly, cold –challenge did not trigger overt M2-like state and failed to induce tyrosine hydroxylase expression in adipose tissue macrophages of control or MIKO mice. These results show that IGF1 signaling shapes the macrophage activation phenotype.

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Section: Resultsmentioning

confidence: 99%

IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge

et al. 2017

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“…These effects persist for at least 6 weeks following clearance of the worm infection in mice, suggesting that resident immune reprogramming is sustainable. It is interesting that as the developed world has seen a gradual decrease in helminth infections, a concomitant increase in allergic, autoimmune, and metabolic diseases has been witnessed – of course, there are numerous other societal factors that may be responsible for this increase too, such as dietary and lifestyle changes – but the co‐evolution of humans and parasitic worms may have provided a stable metabolic environment that in the absence of worms results in increases in obesity and allergies. A concerted research and clinical effort is seeking to utilize helminth‐derived factors as biologic therapeutics to treat metabolic and inflammatory diseases, and if the key components can be identified without resorting to live worms, the unwanted side effects and inevitable public apprehension over worm‐derived treatments may be overcome.…”

Section: Targeting Eosinophil Function and Activity For Metabolic Thementioning

confidence: 99%

Defining Eosinophil Function in Adiposity and Weight Loss

et al. 2018

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Despite promising early work into the role of immune cells such as eosinophils in adipose tissue (AT) homeostasis, recent findings revealed that elevating the number of eosinophils in AT alone is insufficient for improving metabolic impairments in obese mice. Eosinophils are primarily recognized for their role in allergic immunity and defence against parasitic worms. They have also been detected in AT and appear to contribute to adipose homeostasis and drive energy expenditure, but the underlying mechanisms remain elusive. It has long been recognized that immune cells such as macrophages respond to external signals to regulate adipose homeostasis and energy balance, however, less is known about the relevance of eosinophil activity in AT. As the authors propose in this review, given recent debate over the relative importance of their tissue-specific abundance, the stage is now set for exploring the functionality and activation states of AT eosinophils.

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“…Thus, it is likely that the balance between Th1 and Th2 responses plays a decisive role in the regulation of obese adipose tissue inflammation. Concomitant with increased M1 polarization, the predominance of Th1 response over Th2 response is one of the well-known characters of obesity-induced systemic inflammation as well as adipose tissue inflammation [8,14]. For example, increased IFN-g secreting T helper cells in blood and adipose tissue support skewed Th1/Th2 response in obesity [39,40].…”

Section: Introductionmentioning

confidence: 99%

Adipocyte CD1d determines adipose inflammation and insulin resistance in obesity

Park

Kim

2018

Adipocyte

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Obesity-induced adipose tissue inflammation is regulated by various immune cells for innate and adaptive immunity. Among adipose tissue immune cells, it has been proposed that invariant Natural Killer T (iNKT) cells play crucial roles in anti-inflammatory responses in obesity. iNKT cells recognize 'lipid' antigens loaded on CD1d of antigen presenting cells and modulate immune responses by secreting Th1 or Th2 type cytokines depending on species of lipid antigens, antigen presenting cell types, and environmental cytokine milieu. However, the regulatory mechanisms of antigen presenting cells for adipose iNKT cell stimulation have not been clearly elucidated. Recently, we have reported that CD1d expressing adipocytes could act as an antigen presenting cell for adipose iNKT cells by characterization of adipocyte-specific CD1d knockout (CD1d) mice. Upon high-fat diet (HFD) feeding, CD1d mice aggravated adipose tissue inflammation and insulin resistance compared with CD1d mice. In this commentary, we provide the additional data of adipocyte CD1d-dependent regulation of adipose iNKT cell responses as well as systemic insulin sensitivity. In addition, we discuss how the interaction between adipocytes and iNKT cells would be regulated with the progression of obesity.

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

Cited by 39 publications

References 92 publications

IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge

IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge

Defining Eosinophil Function in Adiposity and Weight Loss

Adipocyte CD1d determines adipose inflammation and insulin resistance in obesity

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