A. Model of ROCK2 regulating in vitro adipogenesis. ROCK2 inhibition (partial ROCK2 deletion or KD025 treatment) facilitates disruption of actin filaments by adipogenic induction, and enhances the activation of PPARγ and C/EBPα by adipogenic induction, resulting in improved beige adipogenesis. B. Schema depicting the actions of ROCK2 inhibition on obesity and insulin resistance. On one hand, ROCK2 inhibition promotes beige adipogenesis in sWAT and activates the thermogenic program in all fat depots leading to increased energy expenditure and reduced fat mass, notably the visceral fat mass. On the other hand, ROCK2 inhibition increases insulin signaling through increased IRS1-mediated PI3K activation, resulting in increased insulin sensitivity, notably in the visceral fat mass. Together, these two positively interacted mechanisms reduce age-related or diet-induced obesity and insulin resistance. Red lines and words indicate the actions of ROCK2 inhibition on beige adipogenesis (A) and age-related or diet-induced obesity and insulin resistance (B).