Taste Receptor Type 1 Member 3 Mediates Cognitive Impairment in Diet-Induced Obese Mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE215332 | GEO | 2024/10/11
REPOSITORIES: GEO
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Project description:Accumulating studies support that the western diet (WD), a diet comprised of saturated fat and sugary drinks, contributes to the pathogenesis of anxiety disorders, the most prevalent mental disorders worldwide. However, the underlying mechanisms by which WD causes anxiety, remain unclear. Abundant expression of taste receptor type 1 member 3 (TAS1R3) is identified in the hypothalamus, a key brain area involved in both sensing peripheral nutritional signals and regulating anxiety. Thus, we investigated the role of the hypothalamic TAS1R3 in WD-induced anxiety using wild-type (WT) and Tas1r3 deficient (Tas1r3-/-) mice fed a normal diet (ND) or WD for 12 weeks. We evaluated anxiety levels with the open field test and the elevated plus maze test. Behavior tests showed WD increased anxiety in WT mice, whereas Tas1r3-/- mice were protected from WD-induced anxiety. Analyzing the hypothalamic transcriptome of WD-fed WT and Tas1r3-/- mice, we found 1,437 genes significantly regulated by Tas1r3 deficiency. In addition, bioinformatic analysis revealed that CREB-mediated maintenance of neuronal regeneration, which can prevent the development of anxiety, was enhanced in WD-fed Tas1r3-/- mice compared to WD-fed WT mice. In addition, in vitro studies further confirmed that Tas1r3 knockdown prevented suppression of CREB caused by high levels of glucose, fructose, and palmitic acid in adult hypothalamic neuronal cells. These results imply that TAS1R3 may play a key role in WD-induced alterations in hypothalamic functions, and inhibition of TAS1R3 overactivation in the hypothalamus could offer therapeutic targets to alleviate the effects of the WD on anxiety.
2023-08-05 | GSE216063 | GEO
Project description:Purpose: Excessive intake of a western diet (WD), characterized by high fat and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms through which dietary changes lead to IBD development remain unknown. Here, we generated a murine model of severe intestinal inflammation triggered by long-term WD consumption, which exhibited markedly elevated taste receptor TAS1R3 expression in inflamed bowel tissues. Thus, we hypothesized that nutrient-induced TAS1R3 modulation is central to regulating intestinal inflammation. We tested our hypothesis by analyzing changes in gene expression profiles and inflammatory cell infiltration in the inflamed bowel tissues of WD-fed Tas1r3-deficient mice. Methods: We carried out RNA-Seq of ileum tissue of wild-type (WT) and taste receptor Tas1r3 knockout (Tas1r3−/−) mice fed a normal diet (ND) or western diet (WD) for 10 weeks using Ion Proton System. Raw RNA-seq reads were split into individual samples based on barcodes and quality controlled using the FASTQC tool. The reads were analyzed with Partek Flow software (Partek, St. Louis, MI, USA) (http://www.partek.com/partekgs). The sequence reads that passed quality filters were analyzed at the transcript isoform level. Results: We confirmed that Tas1r3-deficient mice are protected from WD-induced intestinal inflammation. Consistent with little or no phenotypic change in the ND group, the gene expression profiles from the ND-fed Tas1r3−/− and WT mice were similar, whereas the ileal transcriptome profiles from the WD-fed Tas1r3−/− mice were readily distinguishable from those of WD-fed WT mice. Inflammatory cytokines such as Tnfα and Il1b were highly expressed in WD-fed WT mice, whereas Pparg, Tjp3, and Defa27 were highly expressed in WD-fed Tas1r3−/− mice. Importantly, we confirmed that the absence of TAS1R3 caused a significant reduction in the inflammatory response-related signaling pathway; GSEA plots also revealed that the mTOR signaling pathway was greatly suppressed. Most notably, the PPAR signaling pathway was significantly affected by TAS1R3 absence. GSEA confirmed that genes associated with the PPAR signaling pathway were significantly enriched in the set of DEGs between Tas1r3−/− and WT mice in the WD groups. Conclusion: Our data suggest that, due to its suppressive action on mTOR, TAS1R3 might function as an important regulator of the PPAR-γ signaling pathway in the intestinal tract.
2023-04-19 | GSE190059 | GEO
Project description:Tuft cells are an epithelial cell subset critical for initiating type 2 immune responses to parasites and protozoa in the small intestine. To respond to these stimuli, intestinal tuft cells use taste chemosensory signaling pathways, but the role of taste receptors in type 2 immunity is poorly understood. Here, we show that the taste receptor TAS1R3, which detects sweet and umami in the tongue, also regulates tuft cell responses in the distal small intestine. BALB/c mice, which have an inactive form of TAS1R3, as well as Tas1r3-deficient C57BL6/J mice both have severely impaired responses to tuft cell-inducing signals in the ileum including the protozoa Tritrichomonas muris and succinate. In contrast, TAS1R3 is not required to mount an immune response to the helminth Heligmosomoides polygyrus, which infects the proximal small intestine. Examination of uninfected Tas1r3-/- mice revealed a modest reduction in the number of tuft cells in the proximal small intestine but a severe decrease in the distal small intestine at homeostasis. Together, these results suggest that TAS1R3 influences intestinal immunity by shaping the epithelial cell landscape at steady state.
2020-01-09 | GSE140395 | GEO
Project description:Wildtype (WT) and albumin-knockout (AKO) were fed with normal diet. We harvested the liver tissues from WT and AKO mice at 3-week, 8-week, and 10-month of age. We then performed gene expression profiling analysis using data obtained from RNA-seq of the six different liver tissues. Wildtype (WT) and albumin-knockout (AKO) mice were fed with Normal diet (ND) or Western diet (WD) for 8 weeks from the age of 8 weeks. We harvested the liver tissues from WT-ND, WT-WD, AKO-ND, AKO-WD mice . We then performed gene expression profiling analysis using data obtained from RNA-seq of the four different liver tissues. Wildtype (WT) mice fed with HFD from the age of 8 weeks were injected by 17-AAG at the 3rd, 4th, 5th, 6.5th, and 8th weeks of the HFD feeding process. The control group was injected by the solvent. Another group of mice at the same age was fed with normal diet (ND). We harvested the liver tissues ND, Ctrl, and 17-AAG mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of the three different liver tissues.
2023-01-20 | GSE222922 | GEO
Project description:Recent studies suggest that the western diet negatively affects male reproduction, but few underlying molecular mechanisms have been established. Also, several studies have reported TAS1R3 is expressed in testis, epididymis and sperm, but their role in male reproduction remains unknown. To investigate the function of taste receptor TAS1R3 in the male reproductive function under western diet condition, we performed RNA-sequencing analysis on testes from C57BL/6 mice fed long-term (18 weeks) western diet.
2024-12-19 | GSE221433 | GEO
Project description:Many studies have reported that taste receptor TAS1R3 is highly expressed in male reproductive tract, but the role of TAS1R3 in male reproduction and underlying molecular mechanisms remain unknown. To investigate the role of taste receptor TAS1R3 in the male reproduction, we performed RNA-sequenceing analysis on testes from C57BL/6 male mice.
2024-02-07 | GSE226995 | GEO
Project description:To investigate the liver transcriptomics of WT and liver Cullin 3 KO mice on chow diect (CD) and Westrn diet (WD)
2024-04-05 | GSE230518 | GEO
Project description:Aging and unhealthy diets are risks for metabolic diseases including liver cancer. Bile acid receptor farnesoid X receptor (FXR) knockout (KO) mice develop metabolic liver diseases and progress into liver cancer as they age, and Western diet (WD) intake facilitates liver carcinogenesis in those mice. This study aimed to uncover molecular signatures within the gut-liver axis for diet and age-linked liver diseases in FXR-dependent or independent manners. Many more transcripts were changed due to WD intake and aging in WT mice than those in FXR KO mice. In other words, WD intake and aging impact the hepatic transcriptomes and metabolomes in an FXR-dependent manner. In WT mice, WD/aging upregulated inflammation-related genes and downregulated genes involved in oxidative phosphorylation (OXPHOS). Urine metabolomes provided clear distinguishing for differential dietary intake. By contrast, the metabolomes of the liver, serum, or urine could reflect age differences. Further, irrespective of differential diets intake or ages, transcriptomes, metabolomes, and cecal microbiota distinguished WT and FXR KO. Western dietary patterns and aging share molecular commonality with FXR deactivation. Notably, WD, aging, and FXR deactivation commonly altered hepatic cell division-related transcripts (Cenpe, Ect2, Top2a, Kif20a, Tpx2, Nuf2, Kif18b, Aspm, E2f8, and Hmmr), which are associated with overall survival rate in HCC patients. In conclusion, FXR is essential for maintaining metabolic homeostasis in response to WD intake and aging. FXR activation helps to alleviate diet and/or aging-induced metabolic health issues.
2023-02-22 | GSE216375 | GEO
Project description:Liver RNA was collected from three genotypes: WT controls, KCP knockout (KCP-KO) mutants, and KCP-Transgenic (KCP-Tg) overexpressing mice. Mice were fed either a normal diet (ND) or a high fat diet (HFD) for 4 weeks before liver RNA extraction.
2016-01-01 | GSE73594 | GEO
Project description:Numerous studies show dietary carbohydrates (C) affect the sensation of sweetness. However, protein (P) is one of the most critical macronutrients in the diet as well. It is still unclear how carbohydrates and proteins interact to influence sweet taste sensitivity. Here, we use the nutritional geometry framework (NGF) to tackle this problem in Drosophila melanogaster. Our results showed that the combination of high protein and low carbohydrates caused higher taste responses to sucrose stimuli in both sexes. Additionally, transcriptome analysis revealed that the gene expression of glycine, serine, and threonine pathway in the high-protein, low-carbohydrate diet was significantly upregulated, compared to a diet with low protein, and high carbohydrate. We confirmed that serine and threonine supplementation in the high-carbohydrate, low-protein diet enhanced the sucrose sensitivity of flies. Our results demonstrate that sucrose taste sensitivity is affected by the dietary balance of protein and carbohydrates possibly mediated by the change in serine, and threonine. The high protein, low carbohydrate diets enhanced sucrose taste sensitivity.
2023-02-16 | GSE217385 | GEO