| Summary: | The shoot of <i>Urtica dioica</i> is used in several cultures as a vegetable or herb. However, not much has been studied about the potential of this plant when consumed as a whole food/vegetable rather than an extract for dietary supplements. In a 12-week dietary intervention study, we tested the effect of <i>U. dioica</i> vegetable on high fat diet induced obesity and insulin resistance in C57BL/6J mice. Mice were fed ad libitum with isocaloric diets containing 10% fat or 45% fat with or without <i>U. dioica</i>. The diet supplemented with <i>U. dioica</i> attenuated high fat diet induced weight gain (<i>p</i> < 0.005; <i>n</i> = 9), fat accumulation in adipose tissue (<i>p</i> < 0.005; <i>n</i> = 9), and whole-body insulin resistance (HOMA-IR index) (<i>p</i> < 0.001; <i>n</i> = 9). Analysis of gene expression in skeletal muscle showed no effect on the constituents of the insulin signaling pathway (AKT, IRS proteins, PI3K, GLUT4, and insulin receptor). Notable genes that impact lipid or glucose metabolism and whose expression was changed by <i>U. dioica</i> include fasting induced adipocyte factor (FIAF) in adipose and skeletal muscle, peroxisome proliferator-activated receptor-α (Ppar-α) and forkhead box protein (FOXO1) in muscle and liver, and Carnitine palmitoyltransferase I (Cpt1) in liver (<i>p</i> < 0.01). We conclude that <i>U. dioica</i> vegetable protects against diet induced obesity through mechanisms involving lipid accumulation and glucose metabolism in skeletal muscle, liver, and adipose tissue.
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