One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice

Abstract

A high-fat diet (HFD) induces inflammation in systemic organs including the hypothalamus, resulting in obesity and diabetes. The vagus nerve connects the visceral organs and central nervous system, and the gastric-derived orexigenic peptide ghrelin transmits its starvation signals to the hypothalamus via the vagal afferent nerve. Here we investigated the inflammatory response in vagal afferent neurons and the hypothalamus in mice following one day of HFD feeding. This treatment increased the number of macrophages/microglia in the nodose ganglion and hypothalamus. Furthermore, one-day HFD induced expression of Toll-like receptor 4 in the goblet cells of the colon and upregulated mRNA expressions of the proinflammatory biomarkers Emr1, Iba1, Il6, and Tnfα in the nodose ganglion and hypothalamus. Both subcutaneous administration of ghrelin and celiac vagotomy reduced HFD-induced inflammation in these tissues. HFD intake triggered inflammatory responses in the gut, nodose ganglion, and subsequently in the hypothalamus within 24 h. These findings suggest that the vagal afferent nerve may transfer gut-derived inflammatory signals to the hypothalamus via the nodose ganglion, and that ghrelin may protect against HFD-induced inflammation.

Energy‑dense diet triggers changes in gut microbiota, reorganization of gut‑brain vagal communication and increases body fat accumulation

“…The pro-inflammatory action of the HFD has been also reported in the NG and hypothalamus (Waise et al 2015, Yi et al 2012). Taken together, these results suggest that a HFD weakens neuroprotective signaling and promotes inflammation in the brain feeding centers, which may lead to increased food intake and obesity.…”

“…Microglia activation is involved in neuronal circuit remodeling (Kettenmann et al 2013) and has been found to control HFD-induced hypothalamic inflammation and loss of neuronal function (Valdearcos et al 2014). Interestingly, HFD-induced hypothalamic inflammation is significantly reduced by vagotomy (Lee et al 2015, Waise et al 2015) suggesting that vagal afferents may transfer bacterial-derived inflammatory signals to the brain feeding centers to trigger microglia activation and neural remodeling.…”

POMC Neurons: From Birth to Death

“…In this atypical inflammation, the hypothalamus, especially the ARC, might be considered as the primary metabolic tissue where inflammatory responses to metabolic changes occur. This is because hypothalamic proinflammatory cytokines (Il1b, Il6, and Tnfα) and NF-κB pathway genes (Ikbkb and Ikbke) are all significantly increased within 1 to 3 days of HFD feeding, whereas inflammation is not yet detected in peripheral organs such as the liver and adipose tissue (135, 136). Therefore, metaflammatory responses occur rapidly in the hypothalamus compared to peripheral tissues.…”

The Vagus Nerve in Appetite Regulation, Mood, and Intestinal Inflammation

“…One recent study suggests that, in rats, the ability of glucose to modulate serotonin signaling in GI vagal afferents is lost after only 3–7 days of exposure to a high fat diet, implying that reduced vagal sensory signaling is affected prior to obesity. Even one day of exposure to a high fat diet increases the recruitment of classically activated macrophages (M1) to the nodose ganglion of mice, suggesting that even short term exposure can induce inflammation in the vagal afferent system 61 .…”