Energy homeostasis plays a significant role in food consumption and body weight regulation with fat intake being an area of particular interest due to its palatability and high energy density. Increasing evidence from humans and animal studies indicate the existence of a taste modality responsive to fat via its breakdown product fatty acids. These studies implicate multiple candidate receptors and ion channels for fatty acid taste detection, indicating a complex peripheral physiology that is currently not well understood. Additionally, a limited number of studies suggest a reduced ability to detect fatty acids is associated with obesity and a diet high in fat reduces an individual's ability to detect fatty acids. To support this, genetic variants within candidate fatty acid receptors are also associated with obesity reduced ability to detect fatty acids. Understanding oral peripheral fatty acid transduction mechanisms and the association with fat consumption may provide the basis of novel approaches to control development of obesity.

Significant experimental evidence supports fat as a taste modality; however, the associated peripheral mechanisms are not well established. Several candidate taste receptors have been identified, but their expression pattern and potential functions in human fungiform papillae remain unknown. The aim of this study is to identify the fat taste candidate receptors and ion channels that were expressed in human fungiform taste buds and their association with oral sensory of fatty acids. For the expression analysis, quantitative RT-PCR (qRT-PCR) from RNA extracted from human fungiform papillae samples was used to determine the expression of candidate fatty acid receptors and ion channels. Western blotting analysis was used to confirm the presence of the proteins in fungiform papillae. Immunohistochemistry analysis was used to localise the expressed receptors or ion channels in the taste buds of fungiform papillae. The correlation study was analysed between the expression level of the expressed fat taste receptors or ion channels indicated by qRT-PCR and fat taste threshold, liking of fatty food and fat intake. As a result, qRT-PCR and western blotting indicated that mRNA and protein of CD36, FFAR4, FFAR2, GPR84 and delayed rectifying K+ channels are expressed in human fungiform taste buds. The expression level of CD36 was associated with the liking difference score (R −0·567, β=−0·04, P=0·04) between high-fat and low-fat food and FFAR2 was associated with total fat intake (ρ=−0·535, β=−0·01, P=0·003) and saturated fat intake (ρ=−0·641, β=−0·02, P=0·008).

Fatty acid taste (FAT) perception is involved in the regulation of dietary fat intake, where impaired FAT is associated with increased fatty food intake. There are a number of FAT receptors identified on human taste cells that are potentially responsible for FAT perception. Manipulating dietary fat intake, and in turn FAT perception, would elucidate the receptors that are associated with long-term regulation of FAT perception. The present study aimed to assess associations between diet-mediated changes to FAT receptors and FAT perception in humans. A co-twin randomised controlled trial was conducted, where each matching twin within a pair were randomly allocated to either an 8-week low-fat (LF; 35 % energy fat) diet. At baseline and week 8, fungiform papillae were biopsied in the fasted state and FAT receptor gene expressions (cluster of differentiation 36 (CD36), free fatty acid receptor 2 (FFAR2), FFAR4, G protein-coupled receptor 84 (GPR84) and a delayed rectifying K⁺ channel (K⁺ voltage-gated channel subfamily A member 2; KCNA2)) were measured using RT-PCR; and FAT threshold (FATT) was assessed using three-alternate forced choice methodology. Linear mixed models were fitted, adjusting for correlation between co-twins. Intake was compliant with the study design, with the LF and HF groups consuming 14·8 and 39·9 % energy from fat, respectively. Expression of FFAR4 increased by 38 % in the LF group (P = 0·023; time–diet interaction P = 0·063). ΔFFAR4 (Δ, week 8–baseline) was associated with Δfat intake (g) ( = −159·4; P < 0·001) and ΔFATT ( = −8·8; P = 0·016). In summary, FFAR4 is involved in long-term diet-mediated changes to FAT perception. Manipulating dietary fat intake, and therefore FFAR4 expression, might aid in reducing taste-mediated passive overconsumption of fatty foods.

ROR1 and ROR2 are receptor tyrosine kinases with altered expression in a range of cancers. Silencing ROR1 or ROR2 in different tumour types has been shown to inhibit proliferation and decrease metastatic potential. The aim of this study was to investigate the role of ROR1 and ROR2 in endometrial cancer via immunohistochemistry (IHC) in a large endometrial cancer patient cohort (n = 499) and through in vitro analysis in endometrial cancer cell lines. Correlation was assessed between ROR1/2 expression and clinicopathological parameters. Kaplan Meier curves were produced for 5-year progression free survival (PFS) and overall survival (OS) with low/moderate versus high ROR1/2 intensity. Cox multivariate regression was applied to analyse the effect of selected covariates on the PFS and OS. The effect of ROR1 and/or ROR2 modulation on cell proliferation, adhesion, migration and invasion was analysed in two endometrial cancer cell lines (KLE and MFE-296). We observed a significant decrease in OS and PFS in patients with high ROR1 expression. ROR1 silencing and ROR2 overexpression significantly inhibited proliferation of KLE endometrial cancer cells and decreased migration. This study supports the oncogenic role of ROR1 in endometrial cancer, and warrants investigation of future application of ROR1-targeting therapies in endometrial cancer patients.

Variability in human taste perception is associated with both genetic and environmental factors. The influence of taste receptor expression on this variability is unknown, in part, due to the difficulty in obtaining human oral tissue that enables quantitative expression measures of taste genes. In a comparison of six current techniques (Oragene RNeasy Kit, Isohelix swab, Livibrush cytobrush, tongue saliva, cheek saliva collection, and fungiform papillae biopsy), we identify the fungiform papillae biopsy is the optimal sampling technique to analyse human taste gene expression. The fungiform papillae biopsy resulted in the highest RNA integrity, enabling amplification of all the assessed taste receptor genes (TAS1R1, TAS1R2, TAS1R3, SCNN1A and CD36) and taste tissue marker genes (NCAM1, GNAT3 and PLCβ2). Furthermore, quantitative expression was observed in a subset of taste genes assessed from the saliva collection techniques (cheek saliva, tongue saliva and Oragene RNA kit). These saliva collection techniques may be useful as a non-invasive alternative sampling technique to the fungiform papillae biopsy. Identification of the fungiform papillae biopsy as the optimal collection method will facilitate further research into understanding the effect of gene expression on variability in human taste perception.