| RELMbeta is an intestinal goblet cell-specific protein constitutively expressed in the colon and inducible in the terminal small intestine. RELMbeta is secreted into the stool and is also detected in serum, suggesting a hormonal function in addition to local intestinal actions. Multiple studies show RELMbeta is involved in the regulation of glucose homeostasis, and is nutritionally regulated. We observed RELMbeta induction by a high fat diet, by gut bacterial colonization, and by parasitic nematode infection. We hypothesized RELMbeta promotes energy efficiency in the context of metabolic stressors by regulating energy metabolism.;To determine the function of RELMbeta, we developed a RELMbeta knockout mouse and determined its metabolic response in models of diet-induced obesity and parasitic nematode infection. No basal phenotypic differences were observed. However, the absence of RELMbeta may be protective against diet-induced obesity in a strain and gender specific manner. The knockout remains lean through decreased deposition of adipose mass and decreased lipid storage within the adipocyte. Energy input, food intake and dietary fat absorption, and components of energy output, locomotor activity and core body temperature, are not altered. However, oxygen consumption is increased in the knockout upon administration of a high fat diet, indicating RELMbeta negatively regulates energy expenditure. This is supported in the parasitic nematode model, where infection led to an induction of RELMbeta and a suppression of energy expenditure in wild-type mice only. In the context of two models of metabolic stress, high fat diet and parasitic nematode infection, initial data indicates RELMbeta negatively regulates energy expenditure.;Interestingly, RELMbeta may also regulate energy homeostasis via alterations in the gut microbiota. We found genotype exerts a modest effect on the overall species diversity of the gut microbiota and that the switch from a standard rodent diet to a high fat diet greatly alters the composition of the gut microbiota. Interestingly, this shift in gut flora can be largely attributed to diet, as the RELMbeta knockout mice were relatively lean in comparison to wild type mice. As a newly described gut hormone, RELMbeta may provide novel insights into the pathogenesis of obesity. |
