|YANG, ZHONGHAN - University Of Maryland
|GRINCHUK, VIKTORIYA - University Of Maryland
|QIN, BOLIN - Integrity Neutraceuticals
|BOHL, JENNIFER - University Of Maryland
|SUN, REX - University Of Maryland
|NOTARI, LUIGI - University Of Maryland
|ZHANG, ZHONGYAN - Johns Hopkins University
|SESAKI, HIROMI - Johns Hopkins University
|SHEA-DONAHUE, TEREZ - University Of Maryland
|ZHAO, AIPING - University Of Maryland
Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2013
Publication Date: 6/15/2013
Citation: Yang, Z., Grinchuk, V., Smith, A.D., Qin, B., Bohl, J.A., Sun, R., Notari, L., Zhang, Z., Sesaki, H., Urban Jr, J.F., Shea-Donahue, T., Zhao, A. 2013. Parasitic nematode-induced modulation of body weight and associated metabolic dysfunction in mouse models of obesity. Infection and Immunity. 81(6):1905-1914.
Interpretive Summary: Obesity is associated with inflammation and changes to the normal metabolism. Parasite nematode (worm) infections can produce an immune response characterized by production of certain proteins called cytokines that can alter some inflammatory diseases. Here we investigated how a parasite infection can affect obesity and related metabolic dysfunction. A mouse strain with a genetic deficiency in Opa1 gene expression in the pancreas caused them to become obese. Both these mice and mice made obese by feeding a high fat diet were infected with a mouse parasitic nematode, Nippostrongylus brasiliensis, prior to or after development of obesity. Changes in body weight, food intake, and changes to blood glucose levels were monitored. When the mice were sacrificed the major organs were weighed and processed for various tests. Prior or concurrent infection of N. brasiliensis decreased weight gain in obese mice and was associated with improved glucose metabolism. Infection in obese mice reduced body weight and fat tissue mass, reduced changes to the liver that was associated with a decreased expression of key enzymes and mediators of fat metabolism, as well as improved glucose metabolism. In addition, the infection resulted in changes to a type of cell found in fat tissue called a macrophage that may be at least partially responsible for the improvements seen in obese parasite infected mice. Worm infection has both preventive and therapeutic effects against the development of obesity and the associated metabolic dysfunction. This research will be useful to other scientists and clinicians who study and treat obesity and related metabolic disorders.
Technical Abstract: Obesity is associated with a chronic low grade inflammation characterized by high level of pro-inflammatory cytokines and mediators implicated in disrupted metabolic homeostasis. Parasitic nematode infection induces a polarized Th2 cytokine response and has been shown to modulate immune-based pathologies. We investigated the effects of parasitic nematode infection against obesity and the associated metabolic dysfunction. Obesity in mice was induced by a genetic deficiency in pancreatic beta cell Opa1 expression or using high-fat diet (HFD) feeding. Mice were infected with Nippostrongylus brasiliensis prior to or after the development of obesity. Changes in body weight, food intake, fasting blood glucose level, and glucose tolerance were monitored. At euthanasia, major organs were weighed and processed for histological and molecular analysis. Prior or concurrent infection of N. brasiliensis decreased weight gain of Opa1KO mice or C57BL/6 mice fed a HFD, and was associated with improved glucose metabolism. Infection in obese mice reduced body weight and adipose tissue mass, ameliorated hepatic steatosis associated with a decreased expression of key lipogenic enzymes and mediators, as well as improved glucose metabolism accompanied by changes in the profile of metabolic hormones. In addition, the infection resulted in a phenotypic change in adipose tissue macrophages characterized by up-regulation of alternative activation markers YM-1 and arginase I. Furthermore, both STAT6-depedent and –independent mechanisms contributed to N. brasiliensis infection-induced effects on body weight and metabolic homeostasis. Parasitic nematode infection has both preventive and therapeutic effects against the development of obesity and the associated metabolic dysfunction.