Abstract
Neuropsychiatric disorders (NPDs) are a huge burden to the patient, their family, and society. NPDs have been greatly associated with cardio-metabolic comorbidities such as obesity, type-2 diabetes mellitus, dysglycaemia, insulin resistance, dyslipidemia, atherosclerosis, and other cardiovascular disorders. Antipsychotics, which are frontline drugs in the treatment of schizophrenia and off-label use in other NPDs, also add to this burden by causing severe metabolic perturbations. Despite decades of research, the mechanism deciphering the link between neuropsychiatric and metabolic disorders is still unclear. In recent years, transient receptor potential Ankyrin 1 (TRPA1) channel has emerged as a potential therapeutic target for modulators. TRPA1 agonists/antagonists have shown efficacy in both neuropsychiatric disorders and appetite regulation and thus provide a crucial link between both. TRPA1 channels are activated by compounds such as cinnamaldehyde, allyl isothiocyanate, allicin and methyl syringate, which are present naturally in food items such as cinnamon, wasabi, mustard, garlic, etc. As these are present in many daily food items, it could also improve patient compliance and reduce the patients’ monetary burden. In this review, we have tried to present evidence of the possible involvement of TRPA1 channels in neuropsychiatric and metabolic disorders and a possible hint towards using TRPA1 modulators to target appetite, lipid metabolism, glucose and insulin homeostasis and inflammation associated with NPDs.
Highlights
Neuropsychiatric disorders (NPDs) such as depression, dementia, psychosis, and bipolar disorder prompt an unhealthy lifestyle, leading to obesity
Association of NPDs with diabetes, obesity or insulin resistance has been an area of interest of researchers for a long time, and the very first reports of metabolic disorders associated with psychiatric disorders trace back to nearly four centuries ago in the 1600s by Thomas Willis [5]
Metabolic comorbidities like Type 2 diabetes mellitus (T2DM), obesity and cardiovascular disorders have been greatly associated with NPDs, and are responsible for reduced life expectancy and poor quality of life in the patients
Summary
Neuropsychiatric disorders (NPDs) such as depression, dementia, psychosis, and bipolar disorder prompt an unhealthy lifestyle (such as cigarette smoking, alcohol consumption, altered eating habits and physical inactivity), leading to obesity. It enhanced the UCP1 expression in intrascapular brown adipose tissue by stimulating noradrenaline secretion via the b2- and b3adrenoceptors following TRPA1 and TRPV1 activation and reduced the visceral fat content in high fat diet-fed rats [73] Other than their involvement in lipid and insulin homeostasis, studies involving TRPA1 agonists suggest that TRPA1 channels are involved in adipokine-cytokine (adiponectin, leptin, TNF- a and IL-6) regulation. In a very recent study, it was observed that co-treatment with dietary TRPA1 agonist, allicin rich garlic juice was able to reverse increased food intake, body weight, impaired glucose homeostasis, elevated PYY, ghrelin and decreased GLP-1, CCK produced by high fat-diet [102] Another major event serving a critical part in appetite regulation is GI inflammation. Pretreatment with HC-030031 eliminated the elevation in GVNA [112]
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