Helminth and Host Crosstalk: New Insight Into Treatment of Obesity and Its Associated Metabolic Syndromes

Abstract

Obesity and its associated Metabolic Syndromes (Mets) represent a global epidemic health problem. Metabolic inflammation, lipid accumulation and insulin resistance contribute to the progression of these diseases, thereby becoming targets for drug development. Epidemiological data have showed that the rate of helminth infection negatively correlates with the incidence of obesity and Mets. Correspondingly, numerous animal experiments and a few of clinic trials in human demonstrate that helminth infection or its derived molecules can mitigate obesity and Mets via induction of macrophage M2 polarization, inhibition of adipogenesis, promotion of fat browning, and improvement of glucose tolerance, insulin resistance and metabolic inflammation. Interestingly, sporadic studies also uncover that several helminth infections can reshape gut microbiota of hosts, which is intimately implicated in the pathogenesis of obesity and Mets. Overall, these findings indicate that the crosstalk between helminth and hosts may be a novel direction for obesity and Mets therapy. The present article reviews the molecular mechanism of how helminth masters immunity and metabolism in obesity.

Keywords: adipokine; fat browning; insulin resistance; macrophages; metabolic inflammation; microbiota; obesity; parasite.

Figure 1

Helminth or its derived molecules induce M2 polarization of macrophages via metabolic reprogramming in obesity. Helminth infection or their derived molecules can induce M2 macrophages polarization along with the setting of complex metabolic reprogramming events in adipose tissue of mice fed by western diet, which provides therapeutic potential for obesity and Mets. PA, palmitic acid; LPS, lipopolysaccharide; GLUT, glucose transporter; G-6P, glucose-6-phosphate; PPP, pentose phosphate pathway; FFA, free fatty acid; FAS, fatty acid synthesis; SDH, succinate dehydrogenase; ACOD1, aconitate decarboxylase 1; CAT, cis-aconitate; EVs, extracellular vesicles; ESPs, excretory-secretory products; PKB, protein kinase B; AMPK, adenosine monophosphate (AMP)-activated protein kinase; PPAR-γ, peroxisome proliferator–activated receptor-γ; FAO, fatty acid oxidation; OXPHOS, oxidative phosphorylation.

Figure 2

The underlying strategies of how helminth or its derived molecules modulate the tissue-specific homeostasis in obesity. Helminth infection or their derived molecules can ameliorate western diet-induced obesity and its associated Mets through inducing M2 macrophage polarization, down-regulating metabolic inflammation, promoting fat browning, attenuating lipid accumulation, ameliorating insulin resistance (through improving the impaired ability of glucose uptake and promoting insulin binding to its receptors) and relieving the dysbiosis of gut microbiota. EVs, extracellular vesicles; ESPs, excretory-secretory products; UCP1, uncoupling protein 1; AMPK, adenosine monophosphate (AMP)-activated protein kinase; PPAR-γ, peroxisome proliferator–activated receptor-γ; LPS, lipopolysaccharide; SCFAs, short-chain fatty acids; ILC2, group 2 innate lymphoid cells.