Experimental Studies to Define the Role of Calcium (Ca2+) and Voltage-Gated Calcium Channel Blockers (vCa-CCB) against Neurosteroid Induced Obesity

Abstract

Introduction: Obesity is closely associated with various types of illness, primarily caused by more calorie intake than body burn. In adipocytes, Calcium (Ca2+) is an important second messenger involved in the regulation of many physiological functions which are essential for survival. In the present research, we have investigated the role of Ca2+ ions in obesity by manipulating cytosolic Ca2+ ion concentration by selective blocking/advancing the Ca2+ ions through the voltage-gated calcium channels. Voltage-gated calcium channel (vCa) plays a key role in regulating intracellular and extracellular Ca2+ concentration. Cytoplasmic level of Ca2+ was manipulated by supplying calcium carbonate and by using vCa blockers i.e. nifedipine- (N-type- vCa-CCB) and ethosuximide (T-type, vCa-CCB). Methods: Obesity was induced by progesterone in female mice and test drugs were co-administered with progesterone whereas sibutramine was used as standard. The treatment was carried out for 28 days, during and after the treatment period various parameters were studied viz food consumption, change in body weight and temperature, the effect on WAT (white adipose tissue, adiposity index, histology of fat pad) and fecal lipid content. Results: Calcium carbonate treated group has shown promising effects in the decrease in body weight by increasing fecal lipid content and lipolysis which was reflected by an increase in body temperature. Ethosuximide also offered significant protection by decreasing the food intake but has not shown any notable effect on fecal fat content, whereas nifedipine has not offered any protection against the obesity induced by neurosteroid. Conclusion: Calcium carbonate has significant anti-obesity activity by including thermogenesis,  and increasing fecal lipid content.