Animal experiment:

Male C57BL/6JSlc mice are 7 weeks of age. The Nrf2 knockout (Nrf2–/–) mouse strain is used in the assay. After 1 week of acclimation, mice are fed normal chow (NC) (containing 2.2% dextrinized cornstarch, 10% kcal from fat), NC containing 0.3% glucoraphanin (NC-GR) (containing 2.2% extract powder), an HFD (containing 2.2% dextrinized cornstarch, 60% kcal from fat), or an HFD containing 0.3% glucoraphanin (HFD-GR) (containing 2.2% extract powder) for 14 weeks. Both the NC and the HFD containing cornstarch or glucoraphanin are prepared. All mice studied are maintained on a 12-h light/dark cycle at 24-26℃ with free access to water and food.

Glucoraphanin, a natural glucosinolate found in cruciferous vegetable, is a stable precursor of the Nrf2 inducer sulforaphane, which possesses antioxidant, anti-inflammatory, and anti-carcinogenic effects.

Glucoraphanin reduces weight gain and increases energy expenditure in HFD-fed mice. Glucoraphanin can improves insulin sensitivity and glucose tolerance in HFD-fed mice. However, Glucoraphanin does not exert antiobesity and insulin-sensitizing effects in Nrf2-/- Mice. Glucoraphanin blocks HFD-induced reduction of Ucp1 protein levels in white adipose depots of wild-type mice but not in Nrf2-/- mice. Glucoraphanin alleviates HFD-induced hepatic steatosis and oxidative stress. Glucoraphanin suppresses HFD-induced proinflammatory activation of macrophages in liver and adipose tissue. Glucoraphanin also decreases circulating LPS and the relative abundance of proteobacteria in the gut microbiomes of HFD-fed mice[1]. Mice with pellets including 0.1% Glucoraphanin (GF) significantly attenuates the decreased social avoidance time in stressed mice. In the 1% sucrose preference test (SPT), treatment with pellets including 0.1% GF significantly attenuates the decreased sucrose preference of stressed mice[2].

[1]. Nagata N, et al. Glucoraphanin Ameliorates Obesity and Insulin Resistance Through Adipose Tissue Browning and Reduction of Metabolic Endotoxemia in Mice. Diabetes. 2017 May;66(5):1222-1236. [2]. Yao W, et al. Role of Keap1-Nrf2 signaling in depression and dietary intake of glucoraphanin confers stress resilience in mice. Sci Rep. 2016 Jul 29;6:30659.