Anti-obesity and metabolic efficacy of the β3-adrenergic agonist, CL316243, in mice at thermoneutrality compared to 22°C.

Objective: Mice are typically housed at environmental temperatures below thermoneutrality, whereas humans live near thermoneutrality. This difference affects energy physiology and, potentially, anti-obesity drug efficacy. Here β3-adrenergic agonist treatment at thermoneutrality (30°C) versus room temperature (22°C) is compared.

Biphasic effect of melanocortin agonists on metabolic rate and body temperature.

The melanocortin system regulates metabolic homeostasis and inflammation. Melanocortin agonists have contradictorily been reported to both increase and decrease metabolic rate and body temperature. We find two distinct physiologic responses occurring at similar doses.

The chemical uncoupler 2,4-dinitrophenol (DNP) protects against diet-induced obesity and improves energy homeostasis in mice at thermoneutrality.

The chemical uncoupler 2,4-dinitrophenol (DNP) was an effective and widely used weight loss drug in the early 1930s. However, the physiology of DNP has not been studied in detail because toxicity, including hyperthermia and death, reduced interest in the clinical use of chemical uncouplers. To investigate DNP action, mice fed a high fat diet and housed at 30 °C (to minimize facultative thermogenesis) were treated with 800 mg/liter DNP in drinking water.

Network analysis of the focal adhesion to invadopodia transition identifies a PI3K-PKCα invasive signaling axis.

In cancer, deregulated signaling can produce an invasive cellular phenotype. We modeled the invasive transition as a theoretical switch between two cytoskeletal structures: focal adhesions and extracellular matrix-degrading invadopodia. We constructed molecular interaction networks of each structure and identified upstream regulatory hubs through computational analyses.