ORCID Profile
0000-0002-1010-516X
Current Organisation
University of Adelaide
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Publisher: Wiley
Date: 29-12-2012
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.PEPTIDES.2017.01.005
Abstract: Food intake is regulated by vagal afferent signals from the stomach. Nesfatin-1 is an anorexigenic peptide produced within the gastrointestinal tract and has well defined central effects. We aimed to determine if nesfatin-1 can modulate gastric vagal afferent signals in the periphery and further whether this is altered in different nutritional states. Female C57BL/6J mice were fed either a standard laboratory diet (SLD) or a high fat diet (HFD) for 12 weeks or fasted overnight. Plasma nucleobindin-2 (NUCB2 nesfatin-1 precursor)/nesfatin-1 levels were assayed, the expression of NUCB2 in the gastric mucosa and adipose tissue was assessed using real-time quantitative reverse-transcription polymerase chain reaction. An in vitro preparation was used to determine the effect of nesfatin-1 on gastric vagal afferent mechanosensitivity. HFD mice exhibited an increased body weight and adiposity. Plasma NUCB2/nesfatin-1 levels were unchanged between any of the groups of mice. NUCB2 mRNA was detected in the gastric mucosa and gonadal fat of SLD, HFD and fasted mice with no difference in mRNA abundance between groups in either tissue. In SLD and fasted mice nesfatin-1 potentiated mucosal receptor mechanosensitivity, an effect not observed in HFD mice. Tension receptor mechanosensitivity was unaffected by nesfatin-1 in SLD and fasted mice, but was inhibited in HFD mice. In conclusion, Nesfatin-1 modulates gastric vagal afferent mechanosensitivity in a nutritional state dependent manner.
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.PEPTIDES.2021.170673
Abstract: This study investigated the nutrient-mediated modulation of total ghrelin (TG) and acyl ghrelin (AG) secretion from the mouse gastric mucosa, and the role of long-chain fatty acid chemosensors, FFAR4 and CD36, in lipid-mediated modulation of TG and AG release. Ex-vivo experiments were conducted using mouse gastric mucosa to examine the effects of nutrients (D-glucose, L-phenylalanine, peptone (mixture of oligopeptides & single amino acids), D-mannitol, α-linolenic acid and fat emulsion (intralipid)) on TG and AG secretion. Additionally, inhibition of FFAR4 and CD36 on α-linolenic acid and intralipid-mediated regulation of TG and AG secretion was assessed. TG and AG secretion were unaffected by glucose and D-mannitol. Peptone stimulated the release of TG and AG. In contrast, L-phenylalanine reduced AG secretion only. Intralipid reduced TG secretion and stimulated AG secretion, and α-linolenic acid reduced AG release, without affecting TG mobilisation. Modulation of ghrelin secretion by lipids occurred in an FFAR4 and CD36-independent manner. Ghrelin secretion is modulated in a nutrient-specific manner by proteins and lipids, with TG and AG displaying independent responses to the same stimuli. In addition, FFAR4 and CD36 do not participate in modulation of TG and AG secretion by α-linolenic acid and intralipid.
Publisher: Public Library of Science (PLoS)
Date: 18-08-2015
Publisher: American Physiological Society
Date: 12-2019
Abstract: Gastric vagal afferent (GVA) sensing of food-related mechanical stimuli is a crucial mechanism in the control of feeding behavior and gastric function. Stress is an important factor contributing to eating disorders and gastric diseases. Chronic stress has been shown to increase the mechanosensitivity of GVAs in mice and to reduce food intake and body weight. Whether the mechanosensitivity of GVAs is modulated by stress hormones is not known. This study aimed to determine the effect of stress hormones on GVA mechanosensitivity. The expression of stress hormone receptors in GVA cell bodies was determined in 8-wk-old male C57BL/6 mice using quantitative RT-PCR combined with laser capture microdissection. The mechanosensitivity of GVAs was determined in the absence and presence of stress hormones using an in vitro single-fiber recording preparation. NR3C1 and CRHR2 (mRNA isoforms of glucocorticoid receptor and CRF2 receptor, respectively) were expressed in GVA neurons. The glucocorticoid receptor agonist corticosterone had no effect on the mechanosensitivity of either tension or mucosal GVAs. Activation of CRF2 receptor by its specific analog, urocortin 3, significantly increased the mechanosensitivity of both tension and mucosal GVAs, an effect prevented by the CRF2 receptor antagonist astressin 2B. In conclusion, activation of CRF2 receptor increases the mechanosensitivity of GVAs. This may contribute to the stress- and CRF2 receptor-associated changes in feeding behavior and gastric function, possibly contributing to the hypersensitivity of GVAs in chronic stress conditions. NEW & NOTEWORTHY Gastric vagal afferents (GVAs) relay food-related signals to the central nervous system, where they are processed, eventually leading to modulation of food intake and gastric function. GVA signaling can be modulated by an array of hormones. Stress has been shown to induce GVA hypersensitivity. This study demonstrates that GVA neurons express subtypes of stress hormone receptors, specifically CRF2. Furthermore, activation of CRF2 receptor increases GVA mechanosensitivity, which could have implications for food intake and gastric function.
Publisher: Wiley
Date: 18-02-2013
Publisher: Frontiers Media SA
Date: 05-04-2018
Publisher: Wiley
Date: 14-07-2020
DOI: 10.1111/NMO.13944
Publisher: Wiley
Date: 26-06-2019
DOI: 10.1111/NMO.13669
Abstract: Stress exposure is known to trigger and exacerbate functional dyspepsia (FD) symptoms. Increased gastric sensitivity to food-related stimuli is widely observed in FD patients and is associated with stress and psychological disorders. The mechanisms underlying the hypersensitivity are not clear. Gastric vagal afferents (GVAs) play an important role in sensing meal-related mechanical stimulation to modulate gastrointestinal function and food intake. This study aimed to determine whether GVAs display hypersensitivity after chronic stress, and whether its interaction with leptin was altered by stress. Eight-week-old male C57BL/6 mice were exposed to unpredictable chronic mild stress or no stress (control) for 8 weeks. The metabolic rate, gastric emptying rate, and anxiety- and depression-like behaviors were determined. GVA mechanosensitivity, and its modulation by leptin, was determined using an in vitro single fiber recording technique. QRT-PCR was used to establish the levels of leptin and leptin receptor mRNA in the stomach and nodose ganglion, respectively. The stressed mice had lower body weight and food intake, and increased anxiety-like behavior compared to the control mice. The mechanosensitivity of mucosal and tension-sensitive GVAs was higher in the stressed mice. Leptin potentiated mucosal GVA mechanosensitivity in control but not stressed mice. The expression of leptin mRNA in the gastric mucosa was lower in the stressed mice. In conclusion, chronic stress enhances GVA mechanosensitivity, which may contribute to the gastric hypersensitivity in FD. In addition, the modulatory effect of leptin on GVA signaling is lost after chronic stress exposure.
Publisher: Wiley
Date: 11-09-2019
DOI: 10.1111/NMO.13711
Abstract: Gastric vagal afferents (GVAs) respond to mechanical stimulation, initiating satiety. These afferents exhibit diurnal fluctuations in mechanosensitivity, facilitating food intake during the dark phase in rodents. In humans, desynchrony of diurnal rhythms (eg, shift work) is associated with a higher risk of obesity. To test the hypothesis that shift work disrupts satiety signaling, the effect of a rotating light cycles on diurnal rhythms in GVA mechanosensitivity in lean and high-fat diet (HDF)-induced obese mice was determined. Male C57BL/6 mice were fed standard laboratory diet (SLD) or HFD for 12 weeks. After 4 weeks, mice were randomly allocated to a normal light (NL 12 hour light: 12 hour dark lights on at zeitgeber time [ZT] 0) or rotating light (RL 3-day NL cycle, 4-day reversed light cycle [lights on: ZT12] repeated) cycle for 8 weeks. At week 12, eight mice from each group were housed in metabolic cages. After 12 weeks, ex vivo GVA recordings were taken at 3 hour intervals starting at ZT0. SLD-RL and HFD-RL gained more weight compared to SLD-NL and HFD-NL mice, respectively. Gonadal fat pad mass was higher in SLD-RL compared to SLD-NL mice. In SLD-NL mice, tension and mucosal receptor mechanosensitivity exhibited diurnal rhythms with a peak at ZT9. These rhythms were lost in SLD-RL, HFD-NL, and HFD-RL mice and associated with d ened diurnal rhythms in food intake. GVA diurnal rhythms are susceptible to disturbances in the light cycle and/or the obese state. This may underpin the observed changes in feeding behavior.
Publisher: Springer Science and Business Media LLC
Date: 30-07-2013
DOI: 10.1038/IJO.2013.138
Abstract: Gastric vagal afferents convey satiety signals in response to mechanical stimuli. The sensitivity of these afferents is decreased in diet-induced obesity. Leptin, secreted from gastric epithelial cells, potentiates the response of vagal afferents to mechanical stimuli in lean mice, but has an inhibitory effect in high-fat diet (HFD)-induced obese mice. We sought to determine whether changes in vagal afferent function and response to leptin in obesity were reversible by returning obese mice consuming a HFD to standard laboratory chow diet (SLD). Eight-week-old female C57BL/6 mice were either fed a SLD (N=20) or HFD (N=20) for 24 weeks. A third group was fed a HFD for 12 weeks and then a SLD for a further 12 weeks (RFD, N=18). An in vitro gastro-oesophageal vagal afferent preparation was used to determine the mechanosensitivity of gastric vagal afferents and the modulatory effect of leptin (0.1-10 nM) was examined. Retrograde tracing and quantitative RT-PCR were used to determine the expression of leptin receptor (LepR) messenger RNA (mRNA) in whole nodose and specific cell bodies traced from the stomach. After 24 weeks, both the HFD and RFD mice had increased body weight, gonadal fat mass, plasma leptin, plasma insulin and daily energy consumption compared with the SLD mice. The HFD and RFD mice had reduced tension receptor mechanosensitivity and leptin further inhibited responses to tension in HFD, RFD but not SLD mice. Mucosal receptors from both the SLD and RFD mice were potentiated by leptin, an effect not seen in HFD mice. LepR expression was unchanged in the whole nodose, but was reduced in the mucosal afferents of the HFD and RFD mice. Disruption of gastric vagal afferent function by HFD-induced obesity is only partially reversible by dietary change, which provides a potential mechanism preventing maintenance of weight loss.
Publisher: Elsevier BV
Date: 09-2015
Publisher: American Physiological Society
Date: 02-2021
Abstract: This study provides first evidence that gastric vagal afferent signaling is attenuated during pregnancy and inversely associated with meal size. Growth hormone attenuated mechanosensitivity of gastric vagal afferents, adding support that increases in maternal growth hormone may mediate adaptations in gastric vagal afferent signaling during pregnancy. These findings have important implications for the peripheral control of food intake during pregnancy.
Publisher: Wiley
Date: 28-08-2013
DOI: 10.1111/APHA.12154
Abstract: Neuropeptide W (NPW) is an endogenous ligand for the receptors GPR7 and GPR8 and is involved in central regulation of energy homeostasis. NPW in the periphery is found in gastric gastrin (G) cells. In the stomach, energy intake is influenced by vagal afferent signals, so we aimed to determine the effect of NPW on mechanosensitive gastric vagal afferents under different feeding conditions. Female C57BL/6 mice (N > 10 per group) were fed a standard laboratory diet (SLD), high-fat diet (HFD) or were food restricted. The relationship between NPW immunopositive cells and gastric vagal afferent endings was determined by anterograde tracing and NPW immunohistochemistry. An in vitro gastro-oesophageal preparation was used to determine the functional effects of NPW on gastric vagal afferents. Expression of NPW in the gastric mucosa and GPR7 in whole nodose ganglia was determined by quantitative RT-PCR (QRT-PCR). The expression of GPR7 in gastric vagal afferent neurones was determined by retrograde tracing and QRT-PCR. Neuropeptide W immunoreactive cells were found in close proximity to traced vagal afferents. NPW selectively inhibited responses of gastric vagal tension receptors to stretch in SLD but not HFD or fasted mice. In the nodose ganglia, GPR7 mRNA was specifically expressed in gastric vagal afferent neurones. In fasted mice gastric mucosal NPW and nodose GPR7, mRNA was reduced compared with SLD. A HFD had no effect on gastric NPW mRNA, but down-regulated nodose GPR7 expression. Neuropeptide W modulates gastric vagal afferent activity, but the effect is dynamic and related to feeding status.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.PHYSBEH.2018.06.039
Abstract: Gastric vagal afferents play an important role in the peripheral control of food intake. Apelin, a central appetite regulating hormone, is also abundantly released from the stomach. Whether apelin modulates gastric vagal afferent signalling is unknown. We aimed to determine whether apelin modulates gastric vagal afferent signalling under different states of nutrition. Female C57BL/6 mice were fed either a standard laboratory diet (SLD) or a high fat diet (HFD) for 12 weeks. An in vitro gastric vagal afferent preparation was used to determine the effect of apelin on gastric vagal afferent mechanosensitivity in SLD mice, fed ad libitum or fasted overnight, and HFD mice. To determine the signalling pathway of apelin via gastric vagal afferents, we determined the expression of apelin receptor (APJ receptor) in the gastric mucosa, the whole nodose ganglion and in gastric vagal afferent neurons innervating the stomach using retrograde tracing and real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The location of apelin and APJ receptor within the gastric mucosa was determined by immunohistochemistry. Expression of apelin and APJ receptor mRNA in gastric mucosa was determined using qRT-PCR. Apelin inhibited the response of gastric mucosal vagal afferents to mucosal stroking in fasted SLD mice, but not in mice fed ad libitum a SLD or HFD. Apelin inhibited the response of gastric tension sensitive afferents to circular stretch in SLD mice fed ad libitum or fasted, an effect not observed in HFD mice. APJ receptor mRNA was detected in the gastric mucosa and whole nodose ganglion, but not specifically in gastric vagal afferents neurons. In the gastric mucosa, APJ receptor immunoreactive cells were co-localised or closely associated with apelin containing cells and co-localised with serotonin, gastrin, histamine and gastric intrinsic factor containing cells. In conclusion, apelin modulates gastric vagal afferent signalling in a nutritional status dependent manner. Further, apelin modulates gastric vagal afferents through an indirect pathway, possibly through the release of hormones eptides from the gastric mucosa.
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.PHYSBEH.2015.06.016
Abstract: Food intake is regulated by vagal afferent signals from the stomach. Adiponectin, secreted primarily from adipocytes, also has a role in regulating food intake. However, the involvement of vagal afferents in this effect remains to be established. We aimed to determine if adiponectin can modulate gastric vagal afferent (GVA) satiety signals and further whether this is altered in high fat diet (HFD)-induced obesity. Female C57BL/6J mice were fed either a standard laboratory diet (SLD) or a HFD for 12weeks. Plasma adiponectin levels were assayed, and the expression of adiponectin in the gastric mucosa was assessed using real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The location of adiponectin protein within the gastric mucosa was determined by immunohistochemistry. To evaluate the direct effect of adiponectin on vagal afferent endings we determined adiponectin receptor expression in whole nodose ganglia (NDG) and also specifically in GVA neurons using retrograde tracing and qRT-PCR. An in vitro preparation was used to determine the effect of adiponectin on GVA response to mechanical stimulation. HFD mice exhibited an increased body weight and adiposity and showed delayed gastric emptying relative to SLD mice. Plasma adiponectin levels were not significantly different in HFD compared to SLD mice. Adiponectin mRNA was detected in the gastric mucosa of both SLD and HFD mice and presence of protein was confirmed immunohistochemically by the detection of adiponectin immunoreactive cells in the mucosal layer of the stomach. Adiponectin receptor 1 (ADIPOR1) and 2 (ADIPOR2) mRNA was present in both the SLD and HFD whole NDG and also specifically traced gastric mucosal and muscular neurons. There was a reduction in ADIPOR1 mRNA in the mucosal afferents of the HFD mice relative to the SLD mice. In HFD mice adiponectin potentiated gastric mucosal afferent responses to mucosal stroking, an effect not observed in SLD mice. Adiponectin reduced the responses of tension receptors to circular stretch to a similar extent in both SLD and HFD mice. In conclusion, adiponectin modulates GVA satiety signals. This modulatory effect is altered in HFD-induced obesity. It remains to be conclusively determined whether this modulation is involved in the regulation of food intake and what the whole animal phenotypic consequence is.
Publisher: Wiley
Date: 03-05-2017
DOI: 10.1111/APHA.12884
Abstract: Neuropeptide W is the endogenous ligand for G-protein-coupled receptors GPR7 and GPR8. In this review, we summarize findings on the distribution of neuropeptide W and its receptors in the central nervous system and the periphery, and discuss the role of NPW in food intake and energy homeostasis.
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.PEPTIDES.2014.09.003
Abstract: Neuropeptide W (NPW) is secreted from gastrin (G) cells in the stomach in response to food intake. The mechanisms underlying food intake-induced regulation of gastric NPW is largely unknown. We hypothesized that specific macronutrients were responsible for food-induced NPW secretion. We evaluated the acute effects of fat, carbohydrate and protein on plasma NPW concentrations in humans and mice. The effect of different nutrients on expression of NPW in the antral stomach was also determined in mice. Primary cell cultures of mouse gastric antral mucosal cells were used to investigate the signaling pathway of NPW expression. Plasma NPW concentrations did not change after nutrient ingestion in either humans or mice. NPW mRNA expression and the number of NPW positive cells in the mouse antrum were increased in mice gavage fed with protein or glucose, but not lipid. In primary antral mucosal cell culture, NPW mRNA expression was stimulated by l-phenylalanine, but not glucose. Calcium-sensing receptor (CaSR) positive cells were largely co-localized with NPW in mouse gastric antral mucosal cells, and NPW mRNA expression was inhibited by a selective antagonist of CaSR NPS2143. However, the l-phenylalanine-induced increase in NPW expression was not affected by NPS2143. In conclusion, these studies indicated an inconsistency between plasma and gastric NPW expression in response to nutrient ingestion, suggesting food induced gastric NPW expression may play a more important role locally. Moreover, glucose and especially protein are potent regulators of gastric NPW, via distinct mechanisms.
Publisher: Society for Neuroscience
Date: 14-05-2018
DOI: 10.1523/JNEUROSCI.0052-18.2018
Abstract: Mechanosensitive gastric vagal afferents (GVAs) are involved in the regulation of food intake. GVAs exhibit diurnal rhythmicity in their response to food-related stimuli, allowing time of day-specific satiety signaling. This diurnal rhythmicity is ablated in high-fat-diet (HFD)-induced obesity. Time-restricted feeding (TRF) has a strong influence on peripheral clocks. This study aimed to determine whether diurnal patterns in GVA mechanosensitivity are entrained by TRF. Eight-week-old male C57BL/6 mice ( N = 256) were fed a standard laboratory diet (SLD) or HFD for 12 weeks. After 4 weeks of diet acclimatization, the mice were fed either ad libitum or only during the light phase [Zeitgeber time (ZT) 0–12] or dark phase (ZT12–24) for 8 weeks. A subgroup of mice from all conditions ( n = 8/condition) were placed in metabolic cages. After 12 weeks, ex vivo GVA recordings were taken at 3 h intervals starting at ZT0. HFD mice gained more weight than SLD mice. TRF did not affect weight gain in the SLD mice, but decreased weight gain in the HFD mice regardless of the TRF period. In SLD mice, diurnal rhythms in food intake were inversely associated with diurnal rhythmicity of GVA mechanosensitivity. These diurnal rhythms were entrained by the timing of food intake. In HFD mice, diurnal rhythms in food intake and diurnal rhythmicity of GVA mechanosensitivity were d ened. Loss of diurnal rhythmicity in HFD mice was abrogated by TRF. In conclusion, diurnal rhythmicity in GVA responses to food-related stimuli can be entrained by food intake. TRF prevents the loss of diurnal rhythmicity that occurs in HFD-induced obesity. SIGNIFICANCE STATEMENT Diurnal control of food intake is vital for maintaining metabolic health. Diet-induced obesity is associated with strong diurnal changes in food intake. Vagal afferents are involved in regulation of feeding behavior, particularly meal size, and exhibit diurnal fluctuations in mechanosensitivity. These diurnal fluctuations in vagal afferent mechanosensitivity are lost in diet-induced obesity. This study provides evidence that time-restricted feeding entrains diurnal rhythmicity in vagal afferent mechanosensitivity in lean and high-fat-diet (HFD)-induced obese mice and, more importantly, prevents the loss of rhythmicity in HFD-induced obesity. These data have important implications for the development of strategies to treat obesity.
No related grants have been discovered for Hui Li.