Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice

Abstract

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.

Cornelian Cherry (Cornus mas L.) Iridoid and Anthocyanin Extract Enhances PPAR-α, PPAR-γ Expression and Reduces I/M Ratio in Aorta, Increases LXR-α Expression and Alters Adipokines and Triglycerides Levels in Cholesterol-Rich Diet Rabbit Model

“…This effect was especially noticeable in the group receiving the higher dose of the extract, where the weight increase was lower by almost 24% compared to the weight increase in the group fed with a cholesterol diet. Weight loss or reduction of weight gain as an effect of iridoids [ 29 , 30 , 31 , 32 ] and anthocyanins [ 33 , 34 , 35 , 36 ] were also observed in other research models. This also applied to models in which compounds from active extract groups were tested, e.g., loganic acid [ 37 ], cyanidin [ 38 ] or pelargonidin [ 39 ].…”

“…leptin, in the hypothalamus. It overstimulates taste buds signaling in response to high-fat diet consumption leading to suppression of orexigenic signaling [ 32 ]. Contrarily, in the case of loganin, an iridoid glycoside isolated from Cornus officinalis , an elevation of leptin serum level in type 2 diabetic db/db mice was observed [ 75 ].…”

TAS1 receptors. An overview of their functions, expression and genetic variations

“…Neither the high-fat diet, nor asperuloside alone induced any mRNA changes. The investigators did not look for mRNA modifications in the hypothalamus or cortex (Ishaq et al, 2021). Bacterial lipopolysaccharides (LPS) were also found to influence gene transcription of taste receptors in taste cells.…”

The Anti-Obesity Compound Asperuloside Reduces Inflammation in the Liver and Hypothalamus of High-Fat-Fed Mice

“…Recent interest has turned to the anti-obesity compound asperuloside (ASP), an iridoid glycoside commonly found in dicotyledonous plant families, including Apocynaceae Verbenaceae, Loganiaceae and Rubiaceae, which has produced promising results in animal models [9][10][11][12]. The mechanisms by which asperuloside exerted its anti-obesity properties are not fully clarified; however, three months of compound administration reduced food intake, body weight, adipose masses as well as plasma levels of triacylglycerol, nonesterified fatty acids and total cholesterol in rats consuming a high-fat diet (HFD) [9,10].…”

“…The mechanisms by which asperuloside exerted its anti-obesity properties are not fully clarified; however, three months of compound administration reduced food intake, body weight, adipose masses as well as plasma levels of triacylglycerol, nonesterified fatty acids and total cholesterol in rats consuming a high-fat diet (HFD) [9,10]. More recently, the anti-obesity properties of asperuloside were confirmed by another animal study in a mouse model of obesity and some mechanisms that could be responsible for its therapeutic effect were also identified [11]. The compound reduced body weight and food intake in rodents consuming HFD by 10.5% and 12.8%, respectively, with no effect on mice eating a standard chow diet.…”