Microarray Analysis of lncRNA and mRNA Reveals Enhanced Lipolysis Along With Metabolic Remodeling in Mice Infected With Larval Echinococcus granulosus

Abstract

Parasitic infection improves metabolic homeostasis in "western diet"-induced obesity through the regulation of adipogenesis. However, the underlying mechanism is not yet fully understood. Using microarray analysis, this study investigated the long noncoding RNA (lncRNA) and messenger RNA (mRNA) profiles of subcutaneous adipose tissues from mice infected with Echinococcus granulosus protoscoleces. A total of 1052 mRNA (541 upregulated, 511 downregulated) and 220 lncRNA (126 upregulated, 94 downregulated) transcripts were differentially expressed (fold change ≥2, P < 0.05) in the infected subcutaneous adipose tissues. When compared with the control group, the infected mice showed a decrease in adipose tissue mass and a reduction in adipocyte size. Indirect calorimetry revealed the change in the energy metabolism after infection, characterized by a lower CO 2 production and O 2 consumption, a sharp decline in carbohydrate oxidation, and a slight increase in fat oxidation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the parasitic infection reprogrammed a complex metabolic network. Notably, "lipoxygenase" and "arginine and proline metabolism" pathways were significantly upregulated while "glycolysis," "tricarboxylic acid cycle," "de novo lipogenesis," and "lipid droplet" pathways were dramatically downregulated. In addition, several key lncRNAs were associated with insulin resistance and adipocyte differentiation. Overall, the present study suggested that E. granulosus infection could enhance lipolysis. Thus, our findings provide novel insights into parasite-mediated metabolic homeostasis, and into the mechanism of hypertrophic adipocytes in obesity.

Immunometabolism: Towards a Better Understanding the Mechanism of Parasitic Infection and Immunity

“…Recent studies have confirmed that ACOD1/itaconate axis links metabolism to immunity in macrophage (123), and has gained lots of interests in immunometabolism field and inflammatory disease models (124,125). Interestingly, our microarray analysis in the fat tissues with larval E. granulosus infection also showed the upregulated levels of SUCNR1, succinodehydrogenase (SDH) and ACOD1 and enriched pathways such as Arginine metabolism and PPAR signaling pathway (67), which is consistent to the M2 polarization of macrophage post infection (Figure 1). These studies highlight the intimate interconnection between immune and metabolism of host and parasite.…”

“…In obese mice, M1 macrophages are accumulated, while parasitic infection often induce M2 polarization of macrophage, thereby reducing the inflammatory response ( 2 ). Lu et al showed that infection of the larval Echinococcus granulosus ( E. granulosus ) can enhance the lipolysis in the fat of mice, which accompanies with enhanced arginine metabolism and PPAR-γ pathway activation ( 67 ). It is well known that arginine metabolism is closely associated with M2 polarization.…”

“…FAO can function in regulating the balance between effector T cells (ETCs) and Tregs. It can promote Treg generation and inhibit their polarization toward ETCs ( 67 ). Gerriets showed that compared with Th17, Tregs have a higher expression of the FAO-related gene like carnitine palmitoyl transferase 1a (CPT1a) ( 106 ).…”

Parasite-Derived Excretory-Secretory Products Alleviate Gut Microbiota Dysbiosis and Improve Cognitive Impairment Induced by a High-Fat Diet

“…Moreover, ESPs derived from parasites can directly inhibit the differentiation of T helper 17 (Th17) cells and polarize macrophages toward the M2 phenotype ( 34 , 36 ), thereby creating an anti-inflammatory microenvironment. In addition, our latest study showed that the larval E. granulosus infection enhances lipolysis, which is accompanied by a decline in carbohydrate oxidation and an increase in fatty oxidation ( 37 ). These studies collectively suggest that larval E. granulosus and its ESPs can effectively remodel the host immunity and metabolism.…”

Understanding Pathogen-host Interplay by Expression Profiles of LncRNA and mRNA in the Liver of Echinococcus Multilocularis-infected Mice

“…Until now, the host lncRNA pro les after Echinococcus infection were mainly identi ed in Echinococcus granulosus-infected mice or cells [20][21][22]. However, the host lncRNA expression pattern and functional activities in response to Em infection are poorly investigated.…”