To explore if the peripheral CB1R antagonist LH-21 will be of benefit to the management of obesity-accompanied hypertension, and further to clarify the underlying mechanism, the impact of LH-21 on obesity-accompanied hypertension was investigated in KKAy mice, a polygenic mouse model of human obesity, T2DM, dyslipidemia, and hypertension (25–27). The gene discussed is CNR1; the disease is obesity due to melanocortin 4 receptor deficiency.