The gustin gene variation at rs2274333 and PROP taster status affect dietary fat perception: a stepwise multiple regression model study.

Gustin, a trophic factor for taste bud development, and its polymorphism at rs2274333 influence taste perception of 6-n-propylthiouracil (PROP) and fungiform papillae (FP) density. The PROP taster status affects dietary fat sensing and body composition. However, there is a paucity of research on the gustin genotype with dietary fat perception, PROP tasting ability, and body mass index (BMI). Thus, taste sensitivity to fat and bitterness was evaluated in 178 healthy individuals. The general labeled magnitude scale was used to determine suprathreshold taste intensity ratings, whereas the alternative forced choice approach was used to estimate the taste-sensing ability. The FP density was assessed by applying blue-colored food dye over the anterior region of the tongue. Restriction fragment length polymorphism was used to detect the genetic polymorphism (rs2274333) in the carbonic anhydrase VI (CA-VI) gene. Fisher's chi-square analysis showed that the CA-VI genotype and allelic frequencies significantly correlated (p<0.001) with the PROP taster status and BMI. Healthy individuals with AA genotypes of the CA-VI polymorphism and PROP super-tasters demonstrated stronger gustatory sensitivity for linoleic acid (LA) with greater FP density in comparison to individuals with AG/GG genotypes and other PROP taster groups. Stepwise forward multiple regression analysis indicates that BMI and PROP taster status significantly influence the LA sensing ability. The suprathreshold intensity rating for LA was also significantly impacted by PROP taster status and CA-VI genotypes, with a variation of 73.3%. Overall, our findings show a relationship between the taste papillae environment and the CA-VI genetic mutation at rs2274333, which influenced the gustatory preference for dietary fat and bitter taste.

Insights on the functional dualism of nitric oxide in the hallmarks of cancer.

Nitric oxide (NO), a gaseous radical, governs a variety of physiological and pathological processes, including cancer, pro-inflammatory signalling, and vasodilation. The family of nitric oxide synthases (NOS), which comprises the constitutive forms, nNOS and eNOS, and the inducible form, iNOS, produces NO enzymatically. Additionally, NO can be generated non-enzymatically from the nitrate-nitrite-NO pathway. The anti- and pro-oxidant properties of NO and its functional dualism in cancer is due to its highly reactive nature. Numerous malignancies have NOS expression, which interferes with the tumour microenvironment to modulate the tumour's growth in both favourable and unfavourable ways. NO regulates a number of mechanisms in the tumour microenvironment, including metabolism, cell cycle, DNA repair, angiogenesis, and apoptosis/necrosis, depending on its concentration and spatiotemporal profile. This review focuses on the bi-modal impact of nitric oxide on the alteration of a few cancer hallmarks.

CD36 genetic polymorphism and salivary cues are associated with oleic acid sensitivity and dietary fat intake.

There is a lack of research on the combined effects of genetic variations (specifically CD36 SNPs-rs1761667 and rs1527483), dietary food habits (vegetarian or not), and the salivary environment on obesity and taste sensitivity, especially in the Indian population. The current study aims to better understand the relationship between impaired taste perception, fat consumption, higher BMI and obesity development by examining the combined association between CD36 SNPs, oleic acid (OA) detection threshold, and food habits among Indian participants. Furthermore, the relationship between oral fatty acid (FAs) sensitivity and taste physiology factors linked to inflammation and salivary proteins was considered. Participants with the minor allele (AA/AG) of CD36 (in both rs1527483 and rs1761667) consumed more fat, particularly saturated FAs (p = 0.0351). Salivary lipopolysaccharide, which causes inflammation, was significantly greater in non-vegetarians with a higher BMI (p < 0.05), and it exhibited a negative correlation (r = -0.232 and p < 0.05) with Ki67 gene expression, a marker for taste progenitor cells. A positive correlation (r = 0.474, p = 0.04) between TLR4 mRNA levels and the OA detection threshold was also observed. Participants with BMI > 25 kg/m2 had substantially higher TNF-α and IL-6 receptor mRNA expression levels, but there were no significant differences between the vegetarian and non-vegetarian groups. However, salivary CA-VI, which has a buffering capability on the oral environment, was lower in non-vegetarian adults with BMI >25. Thus, it was shown that non-vegetarians with overweight and obesity in India were in at-risk groups for the CD36 SNP (AA/AG at rs1761667 and rs1527483) and had higher levels of inflammatory markers, which exacerbated alterations in food behaviour and physiological changes, indicating their relevance in the development of obesity.

Exercise modifies fatty acid perception and metabolism.

AIM: Obesity is a major public health issue, which is associated with several chronic diseases. In rodents, voluntary wheel running (VWR) is a type of exercise that influences ingestive behavior. This study aims to investigate the possible function of VWR activity in the perception of fat taste and if it mitigates the immediate effects of fatty acid (FA) ingestion. METHODS: Male C57BL/6 mice were arbitrarily assigned to either a sedentary (SED) lifestyle or free access to a running wheel after 5 weeks of dietary regimen. Later these mice groups were used in the investigations on fat preference, metabolic tolerance, and electrophysiology. Diet-induced alterations in CD36 and GPR120 expression that are related to fat perception and the capacitative calcium signaling caused by FA in taste bud cells (TBCs) were also examined. RESULTS: In obese groups, VWR temporarily reduced body weight, demonstrated improvement in preference scores for FA, and recovered from a deterioration in glucose homeostasis. In CD36-positive TBCs, electrophysiological investigations showed alterations in [Ca2+ ]i caused by FA. Further, in the TBCs of circumvallate papillae, there are differences in the expression of the genes CD36 and GPR120 between the active and SED controls. Obese mice also show lower incentive salience for long-chain fatty acids (LCFA) and adapted to the reward system of VWR which may lead to improved incentive salience accredited to wheel running. CONCLUSION: In conclusion, this study provides the first evidence that VWR causes orosensory adaptations to fat and appears to alter taste preference for LCFAs.

Tongue papillae density and fat taster status- a cardinal role on sweet and bitter taste perception among Indian population.

Obesity is a complex nutritional disorder that may be influenced by calorie intake and eating behaviours. Aside from many studies, the influence of papillae count on obesity is still debated. Despite the multiple variables connected to weight gain and altered taste perception, determining the association between papillae count and taste sensitivity to fat, sweet and bitter tastes, in particular, has recently become a focus of attention. This study aimed to rule out the relationship between the number of papillae on different areas of the tongue and taste sensitivity in people (n = 150) among the various groups depending on their body mass index (BMI) and fat taste sensitivity. The general labelled magnitude scale (gLMS) was used for the taste sensitivity analysis, and participants were asked to rate the intensity of each concentration of the different tastants. Using a digital camera to obtain a picture of the tongue, the density of the papillae on the tongue was counted manually by three different operators. The study reveals that the total papillae density and BMI had a direct negative correlation (r = -0.43), with papillae density (PD) decreasing as BMI increased. Concurrently, persons with higher BMIs had lower papillae distributions (32.38 ± 1.85 PD/cm2) and significantly lower perceptions of the intensity of fat taste. Further examining papillae density in the anterior front part of the tongue, the front-right section, showed significantly higher papillae distribution (74.04 ± 2.11 PD/cm2) than the front-left section. When considering the sensitivity in the tip of the tongue, middle tongue, and whole mouth, high-sensitivity individuals for fat are more sensitive to both sweet and bitter tastes. Overall, the results of this study demonstrated a strong relationship between taste sensitivity in the Indian population, BMI, and tongue papillae density in various regions of the tongue.

Genetic variation in sweet taste receptors and a mechanistic perspective on sweet and fat taste sensation in the context of obesity.

Taste sensation enables humans to make nutritionally important decisions such as food preference and consumption. It functions as deterministic factors for unpropitious eating behavior, leading to overweight and obesity. The hedonistic feeling on consumption of fat and sugar-rich meals, in particular, has a negative influence on health. In addition, impairment in the taste receptors alters the downstream signaling of taste transduction pathway. Hence, genetic polymorphism in typical taste receptors is a predictor of taste sensitivity variance across individuals. The present review summarizes the effect of a single nucleotide polymorphism (SNP) in sweet taste receptors (T1R2/T1R3) on taste perception among individuals of various body mass index (BMI). Furthermore, in the context of obesity, we discussed the possibility of crosstalk between fat and sweet receptors as well as taste dysfunction in diseased individuals. In overall, a greater understanding of the physiological relationship between taste receptors, altered taste sensitivity, and genetic polymorphisms should lead to more effective obesity prevention approaches.

CD36 and GPR120 mediated orogustatory perception of dietary lipids and its physiological implication in the pygmy mouse Mus booduga.

Fat taste perception has long been concerned in the regulation of dietary fat intake. Substantial experimental evidence defends fat as a sixth taste modality, but its allied peripheral mechanisms are not yet well established. The present study aimed to analyse the diet-induced changes in fat taste perception and its associated physiological variations in Mus booduga. Four groups of animals were used for the present study and were fed any one of the following diet; normal diet (10% fat), low-fat diet (4% fat), high-fat diet (36% fat), or high-fat diet (HFD) (36% fat) + rapeseed oil (HFRDO) (14%) for 9 weeks. The animals were then subjected to metabolic tolerance, fat preference, and conditioned taste aversion studies. Diet-induced alterations in the expression of genes associated with lipogenesis, inflammation, and fat taste (CD36 and GPR120) were analysed. Capacitative calcium signalling induced by both linoleic acid and grifolic acid in taste bud cells (TBCs) was also analysed. In result, both the HFD and HFDRO groups revealed deterioration in glucose homoeostasis and displayed decreased preference scores for fatty acids, which are associated with lower CD36 expression and increased GPR120 expression in TBCs. Furthermore, change in [Ca2+ ]i induced by LA was also compromised in CD36 positive TBCs along with elevated systemic inflammatory and lipidemic responses in both these obese groups. Overall, for the first time, our results support that chronic HFD feeding alters the CD36 and GPR120 mediated fat taste perception in M. booduga.

Anticancer Activity of Leonurus sibiricus L.: Possible Involvement of Intrinsic Apoptotic Pathway.

Liver cancer is the most common cause of mortality in men and women. The aim of this study was to evaluate the methanolic extract of aerial parts of Leonurus sibiricus L (LS) for its anticancer activity on HCC cell lines. Human HCC cell lines, Huh-7 and HSC-T6 were used for cytotoxicity assay, determination of ROS and gene expression analysis (p53, Bcl-2, Bax, caspase-3, caspase-8, and caspase-9). Western blotting was used to assess ERK, AKT, and Caspase-3 activation. HPLC-MS analysis was also performed to determine the phytochemicals present in LS-M extract. LS-M extract has increased the expression of proapoptotic genes, including p53, Bax, and caspase-9 and down-regulated the activation of ERK and Akt. The caspase-3 activity as well as the ROS generation were significantly increased in a dose-dependent manner compared to control. The carotenoids, lutein and beta carotene present in LS-M extract exhibited anticancer activity. In overall, the methanolic extract of LS induces apoptosis in Huh-7 as well as in HSC-T6 cells possibly involving a ROS-mediated mitochondrial signaling pathway. Graphical abstract - The methanolic extract of LS induces apoptosis in Huh-7 as well as in HSC-T6 cells possibly involving a ROS-mediated mitochondrial signaling pathway[Formula: see text].

Anti-Obesity Effect of T. Chebula Fruit Extract on High Fat Diet Induced Obese Mice: A Possible Alternative Therapy.

Occurrence of obesity and its associated metabolic disorders continues to escalate. The present study evaluates the anti-obesity effects of ethanolic fruit extract of Terminalia chebula (EETC) on high fat diet induced obese mice. The bioactive compounds present in the EETC is evaluated by Fourier-transform infrared (FT-IR), Gas chromatography-mass spectrometry (GC-MS), and Liquid chromatography-mass spectrometry (LC-MS) analysis. The effects of EETC on energy intake, glucose tolerance, and various biochemical parameters were analyzed using laboratory mice. Relative gene expression of Fatty acid synthase (FAS), Peroxisome proliferator-activated receptors α (PPARα), Carnitine palmitoyltransferase-1 (CPT-1), Tumor necrosis factor alpha (TNF-α) as well as Interleukin 6 (IL-6) were analyzed in liver and adipose tissues. The findings reveal the hypolipidemic and anti-obesity potential of EETC on high fat fed obese mice. EETC exerts its anti-obesity effects by suppressing lipogenesis through reduction in lipogenic enzyme (FAS) expression, increased fatty acid oxidation via PPARα and CPT-1 and by triggering the anti-inflammatory responses. To our knowledge, this is the first report of the effect of EETC on PPARα and CPT-1 in in vivo.

Fat taste signal transduction and its possible negative modulator components.

The incidence of obesity and its associated diseases including diabetes and various cardiovascular disease continues to escalate. Since the energy homeostasis executes a substantial role in fat-rich food intake and body weight regulation, it grows into a prevalent subject of interest for its strong energy density and high palatability. Over the decade, the notion that the dietary fatty acids convey signaling cues to oro-gustatory system embrace profound ability in understanding its function along with its perception of dietary fats. In this review, recent developments in the field of oleogustus and its downstream signaling mechanism in taste bud cells are analyzed. Notably, we made a brief attempt to expose the possible negative modulator components that had the potential to modulate the distinctive fat signal transduction components and its oro-gustatory mechanism. This review is in-sighted to urge the scientific community to work towards that goal to establish the libraries comprising both chemical and natural fat taste modifiers that adhere to fat taste receptors and alters its gustatory sense to proficiently combat obesity-linked complications.

Differential intracellular localization of Hsp70 in the gill and heart tissue of fresh water prawn Macrobrachium malcolmsonii during thermal stress.

Exposure of organisms to heat stress induces the expression of evolutionarily conserved proteins called the stress proteins or heat shock proteins (HSPs). At the cellular level, HSPs by acting as molecular chaperone prevents the heat induced aggregation of denatured proteins and play a significant role in adaptation to temperature. Among different HSP family members, Hsp70 is the highly conserved and ubiquitously expressed protein. The present study is carried out to detect changes in the localization of Hsp70/Hsc70 in gill and heart tissues of control and heat shocked juveniles of Macrobrachium malcolmsonii that could be correlated with the functional significance of these two isoforms. Two groups of prawn acclimated at 30 °C were exposed to reported optimum Hsp70 induction temperatures of 36 °C and 38 °C for heart and gill, respectively, for a duration of 48 h. These tissues were processed by immunocytochemical methods to detect intra-cellular localization of Hsp70/Hsc70. Western blotting analysis was performed to determine the cytoplasmic or nuclear localization of Hsp70/Hsc70 and band intensity was detected in total lysate, cytosolic and nuclear extracts of gill and heart tissue. The present investigation clearly shows that there are alterations in the intracellular localization of Hsp70/Hsc70 in the cells of the gill and heart tissues of M. malcolmsonii following heat stress. The western blotting results corroborate the results obtained by immunohistochemical localisation. The differential intracellular localization of Hsp70/Hsc70 appears to indicate the functional roles of this stress protein during exposure to thermal stress.