Paper Title
Combination of TRP Channel Dietary Agonists Induces Energy Expending Phenotype to Prevent HFD Associated Alterations in Mice

Abstract
Bioactive dietary constituents activating Transient Receptor Potential (TRP) channels have emerged as promising candidates for the treatment and prevention of metabolic disorders. The present study is an attempt to evaluate novel mechanisms of anti-obesity potential of a dietary TRP-based tri-agonist formed by combination of sub-effective doses of capsaicin (TRPV1 agonist), menthol (TRPM8 agonist) and cinnamaldehyde (TRPA1 agonist) in high fat diet (HFD)-fed mice. Male C57BL/6J mice divided into three groups (n= 8), were fed on normal pellet diet (NPD), or HFD (60% energy by fat) and HFD+CB (combination of capsaicin 0.4mg/Kg, menthol 20mg/Kg and cinnamaldehyde 2mg/Kg; p.o) for 12 weeks. Effects on HFD-induced weight gain, biochemical, histological and genomic changes in the WAT, BAT, liver and hypothalamus tissues were studied. Administration of tri-agonist prevented HFD-induced increase in weight gain, improved altered morphometric parameters, glucose homeostasis and reduced adipose tissue hypertrophy. Tri-agonist supplementation was found to induce WAT browning and promote BAT activation. Enhanced glucose utilization and prevention of lipid accumulation and insulin resistance in the liver was observed in mice supplemented with tri-agonist. The present work provides evidence that the new approach based on combination of sub-effective doses of dietary TRP channel agonists (TRI-AGONIST) can be employed to develop concept-based functional food/nutraceutical for therapeutic and preventive strategies against diet-induced obesity which will improve the overall health.