Herein, in order to obtain more information on the role of TRPC4 and TRPC5 in the metabolic alterations caused by HS diet, we used a dual TRPC4/TRPC5 blocker, ML204, and investigated its effects on body weight, hyperglycaemia, dyslipidaemia, fat tissue accumulation, and tissue inflammation, in comparison with mice fed a standard diet. Here, TRPC5 is linked to Hyperglycemia.