Research Projects

Metabolic complications are a growing health concern globally and in India. Data from the National Family Health Survey (NFHS-4: 2015-2016 and NFHS-5: 2019-2021) indicates that the average Body Mass Index (BMI) has increased significantly: from 18.9% to 22.9% for men and from 20.6% to 24.0% for women over the last five years. Additionally, 13.5% of women and 15.6% of men in India have compromised glucose tolerance capacity, suggesting insulin resistance (NFHS-5: 2019-2021). Similarly, a concurrent increase in climate temperature in combination with modern temperature-controlled housing warrants an even deeper understanding of the thermal contribution to increasing crises of metabolic disorders in the Indian context. Environmental temperature significantly influences the metabolic rates of organisms, a phenomenon intricately linked to factors such as body mass, life stage, activity level, and local climate. Cold exposure below the thermoneutral zone has emerged as a promising therapeutic strategy despite certain adaptive thermoregulatory mechanisms (Saltykova et al., 2018) that undesirably impart a positive energy balance, a known hurdle in the context of metabolic disorders. While thermal cold sensation promotes negative energy balance through nonshivering thermogenesis-induced energy expenditure, it also results in positive energy balance due to peripheral vasoconstriction and heightened food intake (Saltykova et al., 2018). Similarly, pharmacological agents that mimic cold stimulation have also been shown to increase energy expenditure (Khare et al., 2018 & 2019; Sankina et al., 2024) but also showed a reduced glucose uptake in brown adipose tissue (Sankina et al., 2024). Our proposal is based on our findings that α2B-adrenergic receptor knockout (α2B-AR KO) mice exhibit unique temperature preference traits, showing wider thermal aversion boundaries compared to their wild-type counterparts (see technical details). Given the established role of α2B-AR in vasoconstriction and our observations of altered thermoregulation, we hypothesize that blocking the α2B-AR, togather with pharmacological cold mimicking, may inhibit cold-induced vasoconstriction. This inhibition is expected to increase peripheral blood flow and enhance heat loss during both, cold exposure and pharmacological cold mimicking induced non-shivering thermogenesis. Additionally, blocking α2B-AR could also widen thermal aversion boundaries, leading to a reduction in cold-induced compensatory food intake and ultimately preventing a positive energy balance. This may elevate the basal metabolic rate and help combat insulin resistance, obesity, nonalcoholic fatty liver disease, and related complications. The completion of this project will lead to the development of novel, more tolerable options to counteract the increasing incidence of metabolic complications and can also open a new area of research for targeting other metabolic diseases based on knowledge of thermoregulation.