Original Article The Small Polyphenolic Molecule Kaempferol Increases Cellular Energy Expenditure and Thyroid Hormone Activation

Disturbances in energy homeostasis can result in obesity and other metabolic diseases. Here we report a metabolic pathway present in normal human skeletal muscle myo-blasts that is activated by the small polyphenolic molecule kaempferol (KPF). Treatment with KPF leads to an 30% increase in skeletal myocyte oxygen consumption. The mech-anism involves a several-fold increase in cyclic AMP (cAMP) generation and protein kinase A activation, and the effect of KPF can be mimicked via treatment with dibutyryl cAMP. Microarray and real-time PCR studies identified a set of metabolically relevant genes influenced by KPF including peroxisome proliferator–activated receptor co-activator-1, carnitine palmitoyl transferase-1, mitochon-drial transcription factor 1, citrate synthase, and uncoupling protein-3, although KPF itself is not a direct mitochondria