A novel fatty acid analogue triggers CD36-GPR120 interaction and exerts anti-inflammatory action in endotoxemia.

Inflammation is a mediator of a number of chronic pathologies. We synthesized the diethyl (9Z,12Z)-octadeca-9,12-dien-1-ylphosphonate, called NKS3, which decreased lipopolysaccharide (LPS)-induced mRNA upregulation of proinflammatory cytokines (IL-1ß, IL-6 and TNF-α) not only in primary intraperitoneal and lung alveolar macrophages, but also in freshly isolated mice lung slices. The in-silico studies suggested that NKS3, being CD36 agonist, will bind to GPR120. Co-immunoprecipitation and proximity ligation assays demonstrated that NKS3 induced protein-protein interaction of CD36 with GPR120in RAW 264.7 macrophage cell line. Furthermore, NKS3, via GPR120, decreased LPS-induced activation of TAB1/TAK1/JNK pathway and the LPS-induced mRNA expression of inflammatory markers in RAW 264.7 cells. In the acute lung injury model, NKS3 decreased lung fibrosis and inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and nitric oxide (NO) production in broncho-alveolar lavage fluid. NKS3 exerted a protective effect on LPS-induced remodeling of kidney and liver, and reduced circulating IL-1ß, IL-6 and TNF-α concentrations. In a septic shock model, NKS3 gavage decreased significantly the LPS-induced mortality in mice. In the last, NKS3 decreased neuroinflammation in diet-induced obese mice. Altogether, these results suggest that NKS3 is a novel anti-inflammatory agent that could be used, in the future, for the treatment of inflammation-associated pathologies.

Dietary linoleic acid supplementation protects against obesity-induced microglial reactivity in mice.

We investigated whether linoleic acid (LA) supplementation could modulate emotional behavior and microglia-related neuroinflammation. For that, male mice of C57BL/6J genetic background fed either a high-fat diet (HFD) or a standard diet (STD) for 12 weeks, were treated with a vehicle or LA solution for 5 weeks before being evaluated for emotional behavior using a battery of behavioral tests. The animals were subsequently sacrificed and their brains collected and processed for immunofluorescence staining, targeting microglia-specific calcium-binding proteins (IBA-1). Neuroinflammation severity was assessed in multiple hypothalamic, cortical and subcortical brain regions. We show an anxio-depressive-like effect of sustained HFD feeding that was neither alleviated nor worsened with LA supplementation. However, increased IBA-1 expression and microgliosis in the HFD group were largely attenuated by LA supplementation. These observations demonstrate that the anti-neuroinflammatory properties of LA are not restricted to hypothalamic areas but are also evident at the cortical and subcortical levels. This study discloses that neuroinflammation plays a role in the genesis of neuropsychiatric disorders in the context of obesity, and that LA supplementation is a useful dietary strategy to alleviate the impact of obesity-related neuroinflammation.

In Vitro Functional Characterization of Type-I Taste Bud Cells as Monocytes/Macrophages-like Which Secrete Proinflammatory Cytokines.

The sense of taste determines the choice of nutrients and food intake and, consequently, influences feeding behaviors. The taste papillae are primarily composed of three types of taste bud cells (TBC), i.e., type I, type II, and type III. The type I TBC, expressing GLAST (glutamate--aspartate transporter), have been termed as glial-like cells. We hypothesized that these cells could play a role in taste bud immunity as glial cells do in the brain. We purified type I TBC, expressing F4/80, a specific marker of macrophages, from mouse fungiform taste papillae. The purified cells also express CD11b, CD11c, and CD64, generally expressed by glial cells and macrophages. We further assessed whether mouse type I TBC can be polarized toward M1 or M2 macrophages in inflammatory states like lipopolysaccharide (LPS)-triggered inflammation or obesity, known to be associated with low-grade inflammation. Indeed, LPS-treatment and obesity state increased TNFα, IL-1ß, and IL-6 expression, both at mRNA and protein levels, in type I TBC. Conversely, purified type I TBC treated with IL-4 showed a significant increase in arginase 1 and IL-4. These findings provide evidence that type I gustatory cells share many features with macrophages and may be involved in oral inflammation.

Loss of Sour Taste Is the Striking Feature among Four Basic Taste Qualities in Tunisian COVID-19 Patients.

BACKGROUND: Taste disorders (TDs) have been reported to be very common in patients suffering from coronavirus disease 2019 (COVID-19), which is caused by the SARS-CoV-2 virus. In most of the hitherto conducted studies, a gustatory assessment was performed on the basis of surveys or self-reports by patients. The aim of our study was to undertake an objective assessment of four basic taste qualities by conducting tasting sessions that allowed detection thresholds in COVID-19 Tunisian patients and to study their associations with inflammation. METHODS: This analytical cross-sectional study was conducted on 89 patients aged between 21 to 70 years who had been diagnosed with COVID-19. We used Burghart taste strips to assess taste perception of the four taste qualities, i.e., sour, bitter, sweet, and salty. Serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) were measured. RESULTS: Taste disorders were reported by 40.4% of the patients, while objective assessments revealed that 63.8% of participants were suffering from hypogeusia and/or ageusia. Sour taste was the most altered (70.8%) gustatory quality. Patients with severe COVID-19 had significantly lower sour and bitter taste scores when compared to patients with minor/moderate forms. There was no significant association between serum inflammatory markers and taste disorders. However, the relationship between bitter and sweet taste qualities and IL-1ß levels was significant (p = 0.018 and p = 0.041). CONCLUSIONS: Our results demonstrate the interest in the objective assessment of taste dysfunctions in COVID-19 patients.

Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male Mice.

BACKGROUND & AIMS: The spontaneous preference for dietary lipids is principally regulated by 2 lingual fat taste receptors, CD36 and GPR120. Obese animals and most of human subjects exhibit low orosensory perception of dietary fat because of malfunctioning of these taste receptors. Our aim was to target the 2 fat taste receptors by newly synthesized high affinity fatty acid agonists to decrease fat-rich food intake and obesity. METHODS: We synthesized 2 fat taste receptor agonists (FTA), NKS-3 (CD36 agonist) and NKS-5 (CD36 and GPR120 agonist). We determined their molecular dynamic interactions with fat taste receptors and the effect on Ca2+ signaling in mouse and human taste bud cells (TBC). In C57Bl/6 male mice, we assessed their gustatory perception and effects of their lingual application on activation of tongue-gut loop. We elucidated their effects on obesity and its related parameters in male mice fed a high-fat diet. RESULTS: The two FTA, NKS-3 and NKS-5, triggered higher Ca2+ signaling than a dietary long-chain fatty acid in human and mouse TBC. Mice exhibited a gustatory attraction for these compounds. In conscious mice, the application of FTA onto the tongue papillae induced activation of tongue-gut loop, marked by the release of pancreato-bile juice into collecting duct and cholecystokinin and peptide YY into blood stream. Daily intake of NKS-3 or NKS-5 via feeding bottles decreased food intake and progressive weight gain in obese mice but not in control mice. CONCLUSIONS: Our results show that targeting fat sensors in the tongue by novel chemical fat taste agonists might represent a new strategy to reduce obesity.

Association between polymorphisms and hypermethylation of CD36 gene in obese and obese diabetic Senegalese females.

BACKGROUND: Obesity and related metabolic disorders are associated with genetic and epigenetic alterations. In this study, we have examined the association between polymorphisms and hypermethylation of the CD36 gene promoter with obesity in Senegalese females with or without type 2 diabetes mellitus to identify novel molecular markers of these pathologies (obesity and type 2 diabetes mellitus). MATERIALS AND METHODS: The study was conducted in Senegal with healthy lean control, obese, and obese diabetic (age; 49.98 years ± 7.52 vs 50.50 years ± 8.76 vs 51.06 ± 5.78, and body mass index (BMI); 24.19 kg/m2 ± 2.74 vs 34.30 kg/m2 ± 4.41 vs 33.09 kg/m2 ± 4.30). We determined three genetic polymorphisms of CD36 i.e., rs1761667, rs1527483, and rs3211867 by real-time polymerase chain reaction, and methylation of CPG islands of CD36 was assessed by methylation-specific polymerase chain reaction (MS-PCR) in DNA isolated from peripheral blood of each participant. Plasma sCD36 levels and DNA methyltransferase 3a (DNMT3a) levels were determined by enzyme-linked immunosorbent assay (ELISA). According to the standard laboratory protocol, all biochemical parameters were analyzed from fasting serum or plasma. RESULTS: For rs1761667, obese and obese diabetic subjects had statistically significant different parameters depending on the genotypic distribution. These were waist size for obese and HDL cholesterol for obese diabetic, they were significantly higher in subjects harboring GG genotype of rs1761667 (respectively p = 0.04 and p = 0.04). For rs3211867, obese subjects harboring the AA/AC genotype had significantly higher BMI (p = 0.02) and total cholesterol (p = 0.03) than obese subjects harboring the CC genotype. At the same time, the obese diabetic subjects harboring the AA/AC genotype had total cholesterol levels significantly higher than the obese diabetic subjects harboring the CC genotype (p = 0.03). For rs1527483, only the control subjects had statistically significant different parameters depending on the genotypic distribution. The control subjects harboring the GG genotype had a significantly higher BMI than the control subjects harboring the AA/AG genotype (p = 0.003). The CD36 gene methylation was significantly 1.36 times more frequent in obese and obese diabetic compared to lean control (RR = 1.36; p = 0.04). DNMT3a levels were higher in subjects with CD36 gene methylation than in subjects without CD36 gene methylation in each group. Obese diabetic subjects with CD36 gene methylation had significantly fewer plasmas sCD36 (p = 0.03) and more LDL-cholesterol (p = 0.01) than obese diabetic subjects without CD36 gene methylation. In the control group, an increase in sCD36 levels would be associated with a decrease in total cholesterol and triglyceride levels (coef = -7647.56 p = 0.01 and coef = -2528.50 p = 0.048, respectively) would be associated with an increase in LDL cholesterol levels. For the obese group, an increase in sCD36 levels would be associated with an increase in fasting insulin levels (coef = 490.99 p = 0.02) and a decrease in glycated hemoglobin levels (coef = -1196.26 p = 0.03). An increase in the sCD36 levels would be associated with an increase in the triglyceride levels in the obese diabetic group (coef = 9937.41 p = 0.02). The AA/AC genotype of SNP rs3211867 polymorphism was significantly associated with CD36 gene methylation in the control and obese diabetic groups (respectively p = 0.05, p = 0.002; 95% CI). CONCLUSION: These observations suggest that polymorphisms and epigenetic changes in CD36 gene promoters may be implicated in the onset of obesity and its related complication type 2 diabetes mellitus.

Is fat taste associated with diet quality? A cross-sectional study conducted among Tunisian adults.

The Tunisian population has experienced a nutrition transition with an increase in the incidence of obesity. As obesity has been associated with a poor orosensory detection of fat. We hypothesized that poor fat detection could be a driver of poor diet quality. This study examined the association between linoleic acid (LA) detection and adherence to a healthy diet among adult participants. A total of 104 LA taster participants were recruited for this study. Dietary assessment was conducted using the 24 h dietary recall method. Diet quality was assessed by determining the Mediterranean diet (MD) score and Health diet indicator (HDI). The relationship between diet quality and log LA detection threshold was done using adjusted linear regression for age, sex, and daily energy intake (only in the fully adjusted model). The predictive margins model (interaction: anthropometric status x LA threshold) was used to assess the difference between non-obese and subjects with obesity adherence to MD across LA detection values. We have observed that the increase in the concentration of linoleic acid detection by 1 log(mmol/L) is associated with an increase of HDI score by 0.12-point [95% CI: 0.02-0.21] and a decrease of the MD score by -0.14-point [-0.25 to -0.03] in the partially adjusted model. However, only the MD score remained negatively associated with LA detection threshold in the fully adjusted model. The subjects with obesity adherence to the Mediterranean diet was lower than subjects with normal weight for LA concentration less than 0 log(mmol/L). The present study suggests that poor orosensory detection of dietary lipids might be a driver for worsening diet quality. Hence, These subjects might be at risk for obesity and, consequently, exposed cumulatively to the harmful effects of excess adiposity and an unhealthy diet.

Taste of Fat and Obesity: Different Hypotheses and Our Point of View.

Obesity results from a temporary or prolonged positive energy balance due to an alteration in the homeostatic feedback of energy balance. Food, with its discriminative and hedonic qualities, is a key element of reward-based energy intake. An alteration in the brain reward system for highly palatable energy-rich foods, comprised of fat and carbohydrates, could be one of the main factors involved in the development of obesity by increasing the attractiveness and consumption of fat-rich foods. This would induce, in turn, a decrease in the taste of fat. A better understanding of the altered reward system in obesity may open the door to a new era for the diagnosis, management and treatment of this disease.

Circulating mir-21 and mir-146a are associated with increased cytokines and CD36 in Algerian obese male participants.

BACKGROUND: The microRNAs have come up as crucial mediators of energy balance and metabolic control. CD36 is potential biomarker of obesity and metabolic syndrome. This study investigates the concentration of miR-146a and miR-21 and CD 36 in blood samples of obese and healthy young participants. We assessed the association of mir-146a and mir-21 with inflammatory states in Algerian young participants. METHODS: Our study included male obese, without co-morbidities (n = 29), and healthy participants (n = 13). miRNA and CD36 expression was measured by real-time RT-PCR, respectively, in serum and blood. RESULTS: miR-146a and miR-21 concentrations were significantly decreased; however, CD36 expression was increased in obese subjects. Interestingly, miR-146a and miR-21 concentrations were negatively correlated to IL-6, TNF-α, and CD36 in obese participants. CONCLUSION: We demonstrate that the downregulation of miR-146a and miR-21 was associated with upregulation of inflammatory state and increased CD36 expression in obese participants.

Spirulina reduces diet-induced obesity through downregulation of lipogenic genes expression in Psammomys obesus.

The present study evaluates the protective effect of spirulina against diet-induced obesity and metabolic disorders in Psammomys obesus, an animal model of metabolic syndrome. Psammomys obesus lives on a low-energy diet, in order to remain healthy. However, under a standard laboratory chow diet (SLCD), this animal exhibits insulin resistance, which occurs as a result of obesity. Psammomys obesus was maintained on SLCD, in order to evaluate the effect of spirulina on obesity development with a particular focus on glucose and lipid metabolism, as well as the mRNA expression of some pro-inflammatory cytokines. After 12 weeks of treatment with spirulina, there was a significant reduction in body weight gain, plasma glucose, insulin and triglyceride levels. There was also a significant reduction in the mRNA expression of genes involved in lipogenesis and inflammation. Spirulina improved insulin sensitivity, glucose and lipid metabolism. These findings highlight the positive effect of spirulina on weight maintenance.

Cellular and Molecular Mechanisms of Fat Taste Perception.

During the last couples of years, a number of studies have increasingly accumulated on the gustatory perception of dietary fatty acids in rodent models and human beings in health and disease. There is still a debate to coin a specific term for the gustatory perception of dietary fatty acids either as the sixth basic taste quality or as an alimentary taste. Indeed, the psycho-physical cues of orosensory detection of dietary lipids are not as distinctly perceived as other taste qualities like sweet or bitter. The cellular and molecular pharmacological mechanisms, triggered by the binding of dietary long-chain fatty acids (LCFAs) to tongue taste bud lipid receptors like CD36 and GPR120, involve Ca2+ signaling as other five basic taste qualities. We have not only elucidated the role of Ca2+ signaling but also identified different components of the second messenger cascade like STIM1 and MAP kinases, implicated in fat taste perception. We have also demonstrated the implication of Calhm1 voltage-gated channels and store-operated Ca2+ (SOC) channels like Orai1, Orai1/3, and TRPC3 in gustatory perception of dietary fatty acids. We have not only employed siRNA technology in vitro and ex vivo on tissues but also used animal models of genetic invalidation of STIM1, ERK1, Orai1, Calhm1 genes to explore their implications in fat taste signal transduction. Moreover, our laboratory has also demonstrated the importance of LCFAs detection dysfunction in obesity in animal models and human beings.

Management of Childhood Obesity-Time to Shift from Generalized to Personalized Intervention Strategies.

As a major public health concern, childhood obesity is a multifaceted and multilevel metabolic disorder influenced by genetic and behavioral aspects. While genetic risk factors contribute to and interact with the onset and development of excess body weight, available evidence indicates that several modifiable obesogenic behaviors play a crucial role in the etiology of childhood obesity. Although a variety of systematic reviews and meta-analyses have reported the effectiveness of several interventions in community-based, school-based, and home-based programs regarding childhood obesity, the prevalence of children with excess body weight remains high. Additionally, researchers and pediatric clinicians are often encountering several challenges and the characteristics of an optimal weight management strategy remain controversial. Strategies involving a combination of physical activity, nutritional, and educational interventions are likely to yield better outcomes compared to single-component strategies but various prohibitory limitations have been reported in practice. This review seeks to (i) provide a brief overview of the current preventative and therapeutic approaches towards childhood obesity, (ii) discuss the complexity and limitations of research in the childhood obesity area, and (iii) suggest an Etiology-Based Personalized Intervention Strategy Targeting Childhood Obesity (EPISTCO). This purposeful approach includes prioritized nutritional, educational, behavioral, and physical activity intervention strategies directly based on the etiology of obesity and interpretation of individual characteristics.

Antioxidant and Anti-Inflammatory Potential of Polyphenols Contained in Mediterranean Diet in Obesity: Molecular Mechanisms.

Nutrition transition can be defined as shifts in food habits, and it is characterized by high-fat (chiefly saturated animal fat), hypercaloric and salty food consumption at the expense of dietary fibers, minerals and vitamins. Western dietary patterns serve as a model for studying the impact of nutrition transition on civilization diseases, such as obesity, which is commonly associated with oxidative stress and inflammation. In fact, reactive oxygen species (ROS) overproduction can be associated with nuclear factor-κB (NF-κB)-mediated inflammation in obesity. NF-κB regulates gene expression of several oxidant-responsive adipokines including tumor necrosis factor-α (TNF-α). Moreover, AMP-activated protein kinase (AMPK), which plays a pivotal role in energy homeostasis and in modulation of metabolic inflammation, can be downregulated by IκB kinase (IKK)-dependent TNF-α activation. On the other hand, adherence to a Mediterranean-style diet is highly encouraged because of its healthy dietary pattern, which includes antioxidant nutraceuticals such as polyphenols. Indeed, hydroxycinnamic derivatives, quercetin, resveratrol, oleuropein and hydroxytyrosol, which are well known for their antioxidant and anti-inflammatory activities, exert anti-obesity proprieties. In this review, we highlight the impact of the most common polyphenols from Mediterranean foods on molecular mechanisms that mediate obesity-related oxidative stress and inflammation. Hence, we discuss the effects of these polyphenols on a number of signaling pathways. We note that Mediterranean diet (MedDiet) dietary polyphenols can de-regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and NF-κB-mediated oxidative stress, and metabolic inflammation. MedDiet polyphenols are also effective in upregulating downstream effectors of several proteins, chiefly AMPK.

Tongue Leptin Decreases Oro-Sensory Perception of Dietary Fatty Acids.

Leptin, an anorectic hormone, regulates food intake, energy expenditure and body weight. We assessed the implication of tongue leptin in the modulation of oro-sensory detection of dietary fatty acids in mice. The RT-PCR analysis showed that mRNA encoding leptin and leptin receptor (Ob-Rb) was expressed in mice taste bud cells (TBC). Confocal microscopic studies showed that the lipid sensor CD36 was co-expressed with leptin in mice TBC. Silencing of leptin or Ob-Rb mRNA in tongue papillae upregulated preference for a long-chain fatty acid (LCFA), i.e., linoleic acid (LA), in a two-bottle paradigm in mice. Furthermore, tongue leptin application decreased the preference for the LCFA. These results suggest that tongue leptin exerts an inhibitory action on fatty acid preference. In isolated mice TBC, leptin decreased LCFA-induced increases in free intracellular calcium concentrations, [Ca2+]i. Leptin and LCFA induced the phosphorylation of ERK1/2 and STAT-3 and there were no additive or opposite effects of the two agents on the degree of phosphorylation. However, leptin, but not the LCFA, induced phosphoinositide-3-kinase (PI-3-K)-dependent Akt phosphorylation in TBC. Furthermore, leptin induced hyperpolarization, whereas LCFA induced depolarization in TBC. Our study demonstrates that tongue leptin exerts an inhibitory action on oro-sensory detection of a dietary fatty acid by interfering with Ca2+ signaling and membrane potential in mice TBC.

Zizyphus lotus L. fruit attenuates obesity-associated alterations: in vivo mechanisms.

CONTEXT: Zizyphus lotus L., ZL is a Mediterranean plant and widely consumed for its beneficial medicinal properties. Objective: We assessed the effects of ZL fruit on diet-induced obesity. Materials and methods: Male C57BL/6j mice were divided into three groups. Each group received either a standard diet or a high-fat diet, HFD (30% of palm oil, w/v) or a HFD-supplemented with ZL fruit powder (10%, w/w) for six weeks, followed by a six weeks period, in which animals were maintained on the HFD and ZL aqueous extract (1%, w/v). We measured plasma parameters and assessed the expression of key genes involved in energy metabolism and inflammation. Results: ZL fruit improved glycaemia, lipids concentrations and inflammation in obese mice. Discussion and conclusion: Our investigations showed that ZL fruit improved glucose tolerance, dyslipidaemia and fatty liver disease, but not the severity of HFD-induced obesity in mice.

DHA induces Jurkat T-cell arrest in G2/M phase of cell cycle and modulates the plasma membrane expression of TRPC3/6 channels.

We investigated whether docosahexaenoic acid (DHA), a dietary n-3 fatty acid, modulates calcium (Ca2+) signaling and cell cycle progression in human Jurkat T-cells. Our study demonstrates that DHA inhibited Jurkat T-cell cycle progression by blocking their passage from S phase to G2/M phase. In addition, DHA decreased the plasma membrane expression of TRPC3 and TRPC6 calcium channels during T-cell proliferation. Interestingly, this fatty acid increased plasma membrane expression of TRPC6 after 24 h of mitogenic stimulation by phorbol-13-myristate-12-acetate (PMA) and ionomycin. These variations in the membrane expression of TRPC3 and TRPC6 channels were not directly correlated with the mRNA expression, indicating that it was a post-translational phenomenon. DHA increased free intracellular calcium concentrations, [Ca2+]i, via opening TRPC3 and TRPC6 channels. We conclude that the anti-proliferative effect of DHA might involve the modulation of TRPC3 and TRPC6 channels in human T-cells.

Obesity and COVID-19: Oro-Naso-Sensory Perception.

Through a recent upsurge of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, the clinical assessment of most of the coronavirus disease 19 (COVID-19) patients clearly presents a health condition with the loss of oro-naso-sensory (ONS) perception, responsible for the detection of flavor and savor. These changes include anosmia and dysgeusia. In some cases, these clinical manifestations appear even before the general flu-like symptoms, e.g., sore throat, thoracic oppression and fever. There is no direct report available on the loss of these chemical senses in obese COVID-19 patients. Interestingly, obesity has been shown to be associated with low ONS cues. These alterations in obese subjects are due to obesity-induced altered expression of olfacto-taste receptors. Besides, obesity may further aggravate the SARS-CoV-2 infection, as this pathology is associated with a high degree of inflammation/immunosuppression and reduced protection against viral infections. Hence, obesity represents a great risk factor for SARS-CoV-2 infection, as it may hide the viral-associated altered ONS symptoms, thus leading to a high mortality rate in these subjects.

CD36 and GPR120 Methylation Associates with Orosensory Detection Thresholds for Fat and Bitter in Algerian Young Obese Children.

BACKGROUND: The spontaneous preference for dietary fat is regulated by two lingual lipid sensors (CD36 and GPR120) in humans and rodents. Our objective was to investigate whether obesity in children is associated with methylation of lipid sensor genes, and whether this alteration was implicated in altered gustatory perception of fat and bitter and increased preference of palatable foods. METHODS: School children were recruited and classified according to their body mass index (BMI) z-score into two groups: obese and lean children. The detection of orosensory perception for oleic acid and 6-n-propylthiouracil was assessed by using a 3-alternative forced-choice test. After blood DNA extraction, methylation patterns were investigated by methylation-specific PCR. The children were also subjected to a food habit questionnaire. RESULTS: Obese children showed higher lipid and bitter detection thresholds than lean children. Besides, more obese children presented higher methylation level of the CpG sites than lean participants. Interestingly, CD36 and GPR120 gene methylation was associated with high lipid detection thresholds in obese participants. The obese participants preferred highly palatable fat-rich food items, associated with CD36 and GPR120 gene methylation. CONCLUSION: Epigenetic changes in CD36 and GPR120 genes might contribute to low orosensory perception of fat and bitter taste, and might be, consequently, critically involved in obesity in children.