Non-technical summary The enteric nervous system (ENS) is an autonomous nervous system integrated along the gut that controls major gastrointestinal (GI) functions such as motility. Increasing data have demonstrated that nutritional factors can modulate the ENS phenotype and consequently impact upon GI functions. Western diet is central in the development of obesity but surprisingly no study has characterized its impact upon ENS phenotype and functions. We show that Western diet-induced obesity (DIO) prevented age-associated loss in a specific population of enteric neurons leading to an acceleration of gastric emptying. In addition, we showed that neuroprotective effects of DIO likely involved leptin and glial cell line-derived neurotrophic factor (GDNF). This is the first study demonstrating an impact of DIO upon the ENS. These DIO-induced neuroplastic changes in the ENS could be involved in the physiopathology of obesity.Abstract Nutritional factors can induce profound neuroplastic changes in the enteric nervous system (ENS), responsible for changes in gastrointestinal (GI) motility. However, long-term effects of a nutritional imbalance leading to obesity, such as Western diet (WD), upon ENS phenotype and control of GI motility remain unknown. Therefore, we investigated the effects of WD-induced obesity (DIO) on ENS phenotype and function as well as factors involved in functional plasticity. Mice were fed with normal diet (ND) or WD for 12 weeks. GI motility was assessed in vivo and ex vivo. Myenteric neurons and glia were analysed with immunohistochemical methods using antibodies against Hu, neuronal nitric oxide synthase (nNOS), Sox-10 and with calcium imaging techniques. Leptin and glial cell line-derived neurotrophic factor (GDNF) were studied using immunohistochemical, biochemical or PCR methods in mice and primary culture of ENS. DIO prevented the age-associated decrease in antral nitrergic neurons observed in ND mice. Nerve stimulation evoked a stronger neuronal Ca 2+ response in WD compared to ND mice. DIO induced an NO-dependent increase in gastric emptying and neuromuscular transmission in the antrum without any change in small intestinal transit. During WD but not ND, a time-dependent increase in leptin and GDNF occurred in the antrum. Finally, we showed that leptin increased GDNF production in the ENS and induced neuroprotective effects mediated in part by GDNF. These results demonstrate that DIO induces neuroplastic changes in the antrum leading to an NO-dependent acceleration of gastric emptying. In addition, DIO induced neuroplasticity in the ENS is likely to involve leptin and GDNF.

Short-bowel syndrome represents the most common cause of intestinal failure and occurs when the remaining intestine cannot support fluid and nutrient needs to sustain adequate physiology and development without the use of supplemental parenteral nutrition. After intestinal loss or damage, the remnant bowel undergoes multifactorial compensatory processes, termed adaptation, which are largely driven by intraluminal nutrient exposure. Previous studies have provided insight into the biological processes and mediators after resection, however, there still remains a gap in the knowledge of more comprehensive mechanisms that drive the adaptive responses in these patients. Recent data support the microbiota as a key mediator of gut homeostasis and a potential driver of metabolism and immunomodulation after intestinal loss. In this review, we summarize the emerging ideas related to host-microbiota interactions in the intestinal adaptation processes.

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Interactive effects of maternal and weaning high linoleic acid intake on hepatic lipid metabolism, oxylipins profile and hepatic steatosis in offspring.