The ion channel TRPV1 is involved in a wide range of processes including nociception, thermosensation and, more recently discovered, energy homeostasis. Tightly controlling energy homeostasis is important to maintain a healthy body weight, or to aid in weight loss by expending more energy than energy intake. TRPV1 may be involved in energy homeostasis, both in the control of food intake and energy expenditure. In the periphery, it is possible that TRPV1 can impact on appetite through control of appetite hormone levels or via modulation of gastrointestinal vagal afferent signaling. Further, TRPV1 may increase energy expenditure via heat production. Dietary supplementation with TRPV1 agonists, such as capsaicin, has yielded conflicting results with some studies indicating a reduction in food intake and increase in energy expenditure, and other studies indicating the converse. Nonetheless, it is increasingly apparent that TRPV1 may be dysregulated in obesity and contributing to the development of this disease. The mechanisms behind this dysregulation are currently unknown but interactions with other systems, such as the endocannabinoid systems, could be altered and therefore play a role in this dysregulation. Further, TRPV1 channels appear to be involved in pancreatic insulin secretion. Therefore, given its plausible involvement in regulation of energy and glucose homeostasis and its dysregulation in obesity, TRPV1 may be a target for weight loss therapy and diabetes. However, further research is required too fully elucidate TRPV1s role in these processes. The review provides an overview of current knowledge in this field and potential areas for development.

Processes involved in regulation of energy balance and intermediary metabolism are aligned to the light-dark cycle. Shift-work and high fat diet (HFD)-induced obesity disrupt circadian rhythmicity and are associated with increased risk of non-alcoholic fatty liver disease (NAFLD). This study aimed to determine the effect of simulating shift work on hepatic lipid accumulation in lean and HFD-mice. C57BL/6 mice fed a standard laboratory diet (SLD) or HFD for 4wks were further allocated to a normal light (NL)-cycle (lights on:0600-1800hr) or rotating light (RL)-cycle (3-days NL and 4-days reversed (lights on:1800-0600hr) repeated) for 8wks. Tissue was collected every 3hrs beginning at 0600hr. HFD-mice gained more weight than SLD-mice, and RL-mice gained more weight than NL-mice. SLD-NL and HFD-NL mice, but not RL-mice, were more active, had higher respiratory quotients and consumed/expended more energy during the dark phase compared to the light phase. Blood glucose and plasma cholesterol and triglyceride concentrations were elevated in HFD and SLD-RL compared to SLD-NL mice. Hepatic glycogen was elevated in HFD compared to SLD-mice. Hepatic triglycerides were elevated in SLD-RL and HFD-mice compared to SLD-NL. Circadian rhythmicity of hepatic acetyl-CoA carboxylase (ACACA) mRNA was phase shifted in SLD-RL and HFD-NL and lost in HFD-RL mice. Hepatic ACACA protein was reduced in SLD-RL and HFD-mice compared to SLD-NL mice. Hepatic adipose triglyceride lipase was elevated in HFD-NL compared to SLD-NL but lower in RL-mice compared to NL-mice irrespective of diet. -Conclusion: A RL-cycle model of shift-work promotes weight gain and hepatic lipid storage even in lean conditions.

Key pointsr The fine control of food intake is important for the maintenance of a healthy metabolic state. r Gastric vagal afferents (GVAs) are involved in the peripheral regulation of food intake via signalling the degree of distension of the stomach which ultimately leads to feelings of fullness and satiety.r This study provides evidence that endocannabinoids such as anandamide are capable of regulating GVA sensitivity in a concentration-dependent biphasic manner.r This biphasic effect is dependent upon interactions between the CB1, TRPV1 and GHSR receptors.r These data have important implications for the peripheral control of food intake.Abstract Gastric vagal afferents (GVAs) signal to the hindbrain resulting in satiety. Endocannabinoids are endogenous ligands of cannabinoid 1 receptor (CB1) and transient receptor potential vanilloid-1 (TRPV1) channels. The endocannabinoid anandamide (AEA) is expressed in the stomach, and its receptor CB1 is expressed in ghrelin-positive gastric mucosal cells. Further, TRPV1, CB1 and growth hormone secretagogue receptor (ghrelin receptor, GHSR) are expressed in subpopulations of GVA neurons. This study aimed to determine the interaction between TRPV1, CB1, GHSR and endocannabinoids in the modulation of GVA signalling. An in vitro electrophysiology preparation was used to assess GVA mechanosensitivity in male C57BL/6 mice.

Background 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. Methods 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. Key Results 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. Conclusions and Inferences 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.