Impact of obesity on digestive functions and the enteric nervous system, Akronym: EnteNeurObesity
Nutritional Sciences
Final Report Abstract
To the best of our knowledge our studies provide the first comprehensive assessment of altered neural, immune, epithelial and muscle functions in the gut of obese animals. Up to now and in particular when we started the project, it was commonly assumed that inflammatory changes in combination with impaired mucosal barrier functions are crucial for developing gut dysfunctions. We report for the first time altered gut functions and ENS plasticity without impaired mucosal integrity and in the absence of inflammatory signs in the gut wall. Thus, in our animal model we did not observe as severe gut dysfunctions as previously published with other diabetic obese animal models. This questions the common assumption that mucosal inflammation and increased mucosal permeability initiate functional gut disorders in obesity. We would rather suggest the scenario that enteric nervous system plasticity is driving impaired mucosal integrity and inflammation in an advanced obese state. Our findings raise the intriguing question whether the altered functions observed in our prediabetic obese animals that have no impaired mucosal integrity just represent the initial phase in the development of more severe inflammation or whether these changes serve to counteract the threat posed by inflammatory signals from the adipose tissue. It is noteworthy that we actually observed some “positive” side effects of obesity such as a neuroprotection against age related loss of enteric neurons, which is only evident in the gastric enteric nervous system, and an enhanced mucosal barrier function in jejunum. This questions the common believe that obesity per se has deleterious effects in the gut. Our findings emphasizes that obesity is a multistage process with altered gut functions that represent threats as well as protection. An immediate question that arises from our findings is to identify the dietary component that may be used to region-specifically reverse neuronal loss during maturation or improve intestinal barrier function. The challenge will be to apply such a protective diet in a sensible way avoiding the development of obesity and its related comorbidities.
Publications
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Leptin excites enteric neurons of guinea-pig submucous and myenteric plexus. Neurogastroenterol Motil. 2011 Apr;23(4):e165-70
Reichardt F, Krueger D, Schemann M
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Diet-induced obesity has neuroprotective effects in murine gastric enteric nervous system: involvement of leptin and glial cell line-derived neurotrophic factor. J Physiol. 2012 Feb 1;590(Pt 3):533-44
Baudry C, Reichardt F, Marchix J, Bado A, Schemann M, des Varannes SB, Neunlist M, Moriez R
