High-Fat Diet And High Blood Insulin Level Impair Fat Taste Perception And Disrupt Metabolism In Type 2 Diabetic C57BL/6J Mice

Abstract

Introduction: Type 2 diabetes (T2D), frequently accompanied by hyperinsulinemia, is associated with impaired taste sensitivity, which may affect dietary preferences and metabolic health.

Objectives: This study investigates how a high-fat diet (HFD) and hyperinsulinemia influence fat taste perception through disruptions in calcium signaling, while also assessing key metabolic parameters such as glucose homeostasis, lipid profiles, oxidative stress, and inflammation in male C57BL/6J mice.

 Methods: Mice (n=24) were fed either standard (STD) or high-fat diet (HFD) for 15 days, then subdivided into control, HFD, STZ, and HFD-STZ groups (n=6 each). T2D was induced in STZ and HFD-STZ mice via streptozotocin injections (40 mg/kg/bw/day, i.p). Fatty acid preference was evaluated using a two-bottle choice test, and calcium imaging was performed on isolated taste bud cells (TBC). Plasma lipid profiles, TBARS, SOD, GPx, TNF-α, IL-1β, and IL-6 levels were analyzed.

 Results: The STZ group showed increased food and energy intake, while the HFD and HFD-STZ groups exhibited reduced food intake but elevated energy consumption. Glycemia and insulinemia were significantly higher in the HFD, STZ and HFD-STZ groups, with the HFD-STZ and mice displaying insulin resistance. Alterations in lipid profiles and oxidative stress markers were evident, particularly in the HFD and HFD-STZ groups, which also demonstrated elevated pro-inflammatory cytokines and reduced antioxidant activity. Our results revealed a decreased preference for fat in the HFD and HFD-STZ groups, which correlated with suppressed calcium signaling triggered by linoleic acid (LA). Also, the STZ group exhibited a slight preference for the fat solution, with a reduced calcium response in TBC.

Conclusions: These findings highlight the pivotal role of hyperinsulinemia, inflammation and oxidative stress associated to diabetes in impairing fat taste sensitivity and disrupting dietary regulation, emphasizing the importance of managing insulin levels for glycemic control and preserving sensory mechanisms crucial for healthy eating behaviors.