Z13 - Enhancing Thermogenesis in Mice Using Forskolin-Loaded Nanoparticles

Saturday, October 11, 2025

10:00 AM - 11:00 AM PDT

Location: Exhibit Hall F, G & H

Presenting Author(s)

Breanna Herrera

Undergraduate Student
University of Texas at San Antonio
San Antonio, Texas, United States

Co-Author(s)

DZ

David Zhang

Graduate Student
University of Texas At San Antonio, United States

Primary Investigator(s)

Maria A. Gonzalez Porras

Assistant Professor
University of Texas San Antonio
San Antonio, Texas, United States

Introduction: : The process by which organisms generate heat or thermogenesis is critical in the regulation of energy balance and metabolism. In extreme cold environments, insufficient thermogenesis may cause hypothermia, a condition characterized by dangerous drops in core body temperature. UCP1 in brown adipose tissue (BAT) separates oxidative phosphorylation to produce heat, allowing for non-shivering thermogenesis. In addition to activating BAT, external stimuli such as cold exposure or pharmacological agents can induce the 'beiging' of white adipose tissue (WAT), transforming energy-storing white adipocytes into beige adipocytes that express UCP1 and acquire thermogenic capacity. Forskolin, an adenylate cyclase activator, stimulates thermogenesis by activating intracellular cAMP levels that amplify the activation of UCP1 and beige/brown adipocytes. Poor solubility of forskolin in water, however, limits its therapeutic use. This study aims to determine whether forskolin-loaded mesoporous silica nanoparticles (LCMSNs-FSK) could be employed to enhance thermogenesis and heat retention in cold-stressed environments using an in vivo model.

Materials and

Methods: : Male mice (C57BL/6J) were randomly split into two groups of treatment in this study: LCMSNs-FSK and phosphate-buffered saline (PBS). After receiving a 200 µL subcutaneous injection of FSK (20 mg/kg) in the peripheral leg region, the mice spent 3 hours in RT before being placed into a cold chamber (5 ± 2 °C) for 3 hours. While the animals were in the cold chamber, for every 30 minutes, the core temperature was recorded using a rectal thermometer and infrared thermal imaging was also taken at 0.6-0.7 m from the animal to track any changes in surface temperature.

Results, Conclusions, and Discussions:: Within the 3-hour period, shown in Figure 1, LCMSN-FSK's local temperature (A) increased significantly more than the PBS control group. While both groups have initial modest decreases, LCMSN-FSK begins to increase after 2h, surpassing PBS. By the end of the 3-hour period, LCMSN-FSK is showing a clear increase in temperature (~0.5°C), whereas PBS remains below baseline. Additionally, by 3h, the maximum localized temperature (B) was significantly elevated in LCMSN-FSK-treated mice (p < 0.01). Meanwhile, the change in temperature in PBS-treated mice declined further, reaching nearly -2.5 °C. LCMSN-FSK appears to induce a localized warming effect with time that PBS does not.
By comparing the core temperatures of both PBS and LCMSN-FSK (C), all the groups initially drop within the first hour. At 3h, PBS is below baseline temperature, whereas LCMSN-FSK has a steady recovery and rising temperatures. LCMSN-FSK differs from PBS at 1.5h with hugely elevated core temperatures at 2h (p < 0.01) and even more so at 3h (*p < 0.001). LCMSN-FSK, therefore, causes a more sustained core temperature rise than PBS. This study demonstrates that LCMSN-FSK enhances thermoregulation in cold-stressed male mice compared to PBS controls. Mice subjected to LCMSN-FSK by subcutaneous injection developed a slow-developing and sustained localized and core body temperature rise over 3h. The PBS-treated mice continued to drop below baseline.
Infrared imaging detected a localized warming effect at the injection site, in support of peripheral thermogenic activation (Figure 2). The robust thermal effects with LCMSN-FSK are indicative of its promise as a targeted therapeutic strategy for cold-induced hypothermia management. Overall, LCMSN-FSK triggers sustained thermal recovery in cold-challenged mice, indicative of effective thermogenic activation via nanoparticle-based FSK delivery.

Acknowledgements and/or References (Optional): :