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In India, number of people suffering from metabolic disorders such as type 2 diabetes, obesity and cardiovascular diseases is increasing at a very fast pace. Nonshivering thermogenesis has been proposed as a target to counter metabolic syndromes. The sites and targetable mechanisms to increase nonshivering thermogenesis still remain poorly defined. Brown adipose tissue (BAT), beige adipocytes and skeletal muscle have been proposed by different groups as sites of nonshivering thermogenesis in mammals. Hence, key metabolic regulators in these sites can be targeted pharmacologically to treat metabolic disorders. BAT is a purely thermogenic site that expresses a protein called uncoupling protein (UCP) 1, which cause mitochondrial proton dissipation leading to heat production. In beige adipocytes that are located in some of the white adipose tissues, UCP1-mediated as well as UCP1-independent mechanisms form basis for its thermogenesis. While in the skeletal muscle, futile Ca2+-cycling especially by the sarcolipin interaction with Sarcoendoplasmic Ca2+ ATPase (SERCA) forms the major source of muscle heat production. India is rich in indigenous medicinal plants and knowledge of traditional systems of medicine like ayurveda, unani. Several plants and their extracts have been claimed to induce hypoglycaemia and insulin sensitivity in peripherial organs, indicating anti-diabetic properties. This provides opportunity to explore for novel pharmacological agents that can boost the metabolism of the above three sites of nonshivering thermogenesis as anti-diabetic agents. Towards this major long-term goal, we are focusing on following closely related projects;
· Metabolic signatures of sedentary life style:
· Functional determinants of muscle associated with type 2 diabetes:
· Pharmacological agents to counter type 2 diabetes:
· Calsequestrin as a target to treat cardiac arrhythmia:
I am also interested in physiological questions having interface with ecology and evolution. This area includes topics like 1) role of muscle thermogenesis in evolution of vertebrate homeothermy, 2) role of sarcolipin in ectothermic vertebrates, 3) coordinated developmental regulation between muscle and adipose tissue depots in different mammalian groups.