Abstract
Nutrient sensing plays important roles in promoting satiety and maintaining good homeostatic control. Taste receptors (TAS) are located through the gastrointestinal tract, and recent studies have shown they have a relationship with metabolic disorders. The aim of this study was to analyze the jejunal expression of TAS1R2, TAS1R3, TAS2R14 and TAS2R38 in women with morbid obesity, first classified according to metabolic syndrome presence (MetS; n = 24) or absence (non-MetS; n = 45) and then classified according to hepatic histology as normal liver (n = 28) or nonalcoholic fatty liver disease (n = 41). Regarding MetS, we found decreased expression of TAS2R14 in MetS patients. However, when we subclassified patients according to liver histology, we did not find differences between groups. We found negative correlations between glucose levels, triglycerides and MetS with TAS1R3 expression. Moreover, TAS2R14 jejunal expression correlated negatively with the presence of MetS and ghrelin levels and positively with the jejunal Toll-like receptor (TLR)4, peroxisome proliferator-activated receptor (PPAR)-γ, and interleukin (IL)-10 levels. Furthermore, TAS2R38 expression correlated negatively with TLR9 jejunal expression and IL-6 levels and positively with TLR4 levels. Our findings suggest that metabolic dysfunctions such as MetS trigger downregulation of the intestinal TASs. Therefore, taste receptors modulation could be a possible therapeutic target for metabolic disorders.
Highlights
Metabolic syndrome (MetS) is a pathogenic condition characterized by the presence of three or more comorbidities, such as central obesity, insulin resistance, hypertension, and hyperlipidaemia, influenced by overnutrition and a sedentary lifestyle [1,2,3]
The aim of this study was to analyze the jejunal expression of TAS1R2, TAS1R3, TAS2R14 and TAS2R38 in women with morbid obesity, first classified according to metabolic syndrome presence (MetS; n = 24) or absence and classified according to hepatic histology as normal liver (n = 28) or nonalcoholic fatty liver disease (n = 41)
Given that Taste receptors (TAS) have been related to metabolic diseases such as obesity and type 2 diabetes mellitus (T2DM), and our cohort of patients was composed by women with morbid obesity (MO), at first we wanted to analyze TAS differential jejunal relative expression (JRE) according to T2DM presence, but we only had three patients with T2DM in our cohort that presented MetS, and there were no significant differences in TAS (TAS1R3, TAS2R38 and TAS2R14) expressions (p = 0.074, p = 0.857, p = 0.749, respectively)
Summary
Metabolic syndrome (MetS) is a pathogenic condition characterized by the presence of three or more comorbidities, such as central obesity, insulin resistance, hypertension, and hyperlipidaemia, influenced by overnutrition and a sedentary lifestyle [1,2,3]. It has been reported that patients with MetS present chronic low-grade inflammation [5] and oxidative stress [4] with increased risk of suffering type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) [2,6]. NAFLD is defined as the presence of hepatic steatosis in >5% of hepatocytes in the absence of a secondary cause such as alcohol consumption [9]. This chronic disease covers a wide hepatopathological spectrum, beginning with simple steatosis, which may progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma [9,10]. The progression into advanced stages of the disease is promoted by multiple insults, such as epigenetic factors, lipotoxicity, toll-like receptor (TLR) activation and intestinal dysbiosis [11]
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