High-Fat Diet During the Perinatal Period Induces Loss of Myenteric Nitrergic Neurons and Increases Enteric Glial Density, Prior to the Development of Obesity

Abstract

Diet-induced obesity induces peripheral inflammation accompanied by a loss of myenteric neurons. Few studies, however, have investigated the effects of a high fat diet (HFD) on either the development of myenteric neurons or prior to the occurrence of obesity. The present study assessed the effects of maternal HFD on the density and neurochemical phenotype of myenteric ganglia in the upper gastrointestinal tract. Sprague-Dawley rats were fed either a control or HFD (14% or 60% kcal from fat, respectively) from embryonic day 13; the fundus, corpus and duodenum were fixed thereafter at postnatal 2, 4, 6 and 12 weeks of age for subsequent immunohistochemical studies. While myenteric ganglion size did not differ throughout the study, HFD exposure decreased the number of nitrergic neurons by 6 weeks of age in all regions. This decrease was accompanied by a loss of PGP-immunoreactive neurons, suggesting a decline in myenteric neuronal number. HFD also increased myenteric plexus glial cell density in all regions by 4 weeks of age. These changes occurred in the absence of an increase in serum or gastric inflammatory markers. The present study suggests that exposure to a HFD during the perinatal time period results in glial proliferation and loss of inhibitory nitrergic neurons prior to the onset of obesity, suggesting that dietary alterations may affect gastrointestinal functions independently of increased adiposity or glycemic dysregulation.

Impact of Maternal Malnutrition on Gut Barrier Defense: Implications for Pregnancy Health and Fetal Development

“…During intestinal inflammation in adult animals, EGCs respond to pro-inflammatory signals and reverse inflammation-induced ENS damage [85] by driving enteric neuron death through nitric oxide production [41,43,44] and triggering ENS neurogenesis [86]. Previously, EGC proliferation was shown to occur in infant rats whose mothers were fed HF diets perinatally, though mRNA and protein expression of local pro-inflammatory cytokines were unchanged at all postnatal timepoints examined (2, 4, 6, and 12 weeks) [35]. Together with our results, this may suggest that maternal HF diet exposure in utero may reprogram mechanisms in the fetus that establish gut-brain connections and communication and increase EGC development to reduce gut inflammation by the time of birth, thereby negating some of the fetal ENS damage incurred during development.…”

“…In response to both over- [27] and undernutrition [28], collectively known as malnutrition, gut barrier function and integrity can become dysregulated, leading to gut microbial dysbiosis, altered gut function, and a leaky gut barrier. Yet, few studies have elucidated the effects of malnutrition on Paneth cell [29,30,31,32,33] and EGC [34,35] development and function (indeed, none have examined EGCs during undernutrition to our knowledge), or how either of these cells are affected by and/or perpetuate gut dysfunction. Since the rates of both undernutrition and underweight [36], as well as over-nutrition and obesity [36], are increasing worldwide, and a compromised gut barrier is both caused by, and leads to, a variety of immune-related, and chronic diseases, the effects of malnutrition on the gut-host relationship are important to understand.…”

Impact of maternal malnutrition on gut barrier defence: implications for pregnancy health and fetal development.

“…During intestinal inflammation in adult animals, EGCs respond to proinflammatory signals and reverse inflammation-induced ENS damage (90) by driving enteric neuron death through nitric oxide production (49,51,52) and triggering ENS neurogenesis (91). Previously, EGC proliferation was shown to occur in infant rats whose mothers were fed HF diets perinatally, though mRNA and protein expression of local proinflammatory cytokines were unchanged at all postnatal timepoints examined (2, 4, 6, and 12 weeks) (43). Together with our results, this may suggest that maternal HF diet exposure in utero may reprogramme mechanisms in the fetus that establish gut-brain connections and communication and increase EGC development to reduce gut inflammation by the time of birth, thereby negating some of the fetal ENS damage incurred during development.…”

“…In response to both over- (35) and undernutrition (36), collectively known as malnutrition, gut barrier function and integrity can become dysregulated, leading to gut microbial dysbiosis, altered gut function, and a leaky gut barrier. Yet, few studies have elucidated the effects of malnutrition on Paneth cell (37)(38)(39)(40)(41) and EGC (42,43) development and function (indeed, none have examined EGCs during undernutrition to our knowledge), or how either of these cells are affected by and/or perpetuate gut dysfunction. Since the rates of both undernutrition and underweight (44), as well as over-nutrition and obesity (44), are increasing worldwide, and a compromised gut barrier is both caused by, and leads to, a variety of immune-related, and chronic diseases, the effects of malnutrition on the gut-host relationship are important to understand.…”

Digestive Motility Disorders in Nonalcoholic Fatty Liver Disease

“…Известно, что моторика, опорожнение желудка и тонкой кишки играют важную роль в регуляции растяжения желудка и интестинальной экспозиции нутриентов, а соответственно, в контроле ощущений насыщения и пресыщения [7]. В одном из исследований показано, что у мышей, накормленных пищей с высоким содержанием жира, наблюдается снижение холецистокинин-и олеат-индуцированного ингибирования желудочной моторики [8]. В нескольких исследованиях получены данные о замедленном опорожнении желудка в постпрандиальном периоде у лиц с ожирением [9][10][11].…”