Moreover, betaine supplementation alleviated hepatic pathological changes, which were concomitant with attenuated insulin resistance (as shown by improved homeostasis model assessment of basal insulin resistance values and glucose tolerance test) and corrected abnormal adipokine productions (adiponectin, resistin, and leptin). Specifically, 8 Evidence-Based Complementary and Alternative Medicine betaine supplementation enhanced insulin sensitivity in adipose tissue as shown by improved extracellular signalregulated kinases 1/2 and protein kinase B activations. In adipocytes, freshly isolated from mice fed a high-fat diet, pretreatment of betaine enhanced the insulin signaling pathway and improved adipokine productions. Further investigation using whole liver tissues revealed that betaine supplementation alleviated high-fat diet-induced endoplasmic reticulum stress response in adipose tissue as shown by attenuated glucose-regulated protein 78/C/EBP homologous protein (CHOP) protein abundance and c-Jun NH2-terminal kinase activation [71] .