Insights into the role of RNA m6A modification in the metabolic process and related diseases.

According to the latest consensus, many traditional diseases are considered metabolic diseases, such as cancer, type 2 diabetes, obesity, and cardiovascular disease. Currently, metabolic diseases are increasingly prevalent because of the ever-improving living standards and have become the leading threat to human health. Multiple therapy methods have been applied to treat these diseases, which improves the quality of life of many patients, but the overall effect is still unsatisfactory. Therefore, intensive research on the metabolic process and the pathogenesis of metabolic diseases is imperative. N6-methyladenosine (m6A) is an important modification of eukaryotic RNAs. It is a critical regulator of gene expression that is involved in different cellular functions and physiological processes. Many studies have indicated that m6A modification regulates the development of many metabolic processes and metabolic diseases. In this review, we summarized recent studies on the role of m6A modification in different metabolic processes and metabolic diseases. Additionally, we highlighted the potential m6A-targeted therapy for metabolic diseases, expecting to facilitate m6A-targeted strategies in the treatment of metabolic diseases.

Dysphagia as a Manifestation of Endocrine and Metabolic Disorders.

Dysphagia is a common manifestation of endocrine and metabolic diseases. Swallowing is a complex neuromuscular process, with an interplay of sensory and motor function, that has voluntary and involuntary control. Disruptions in any of these processes can cause significant dysphagia. Endocrine disorders and metabolic derangements are systemic conditions that affect multiple organ systems. They contribute to the development of neuropathies, myopathies, and motility disorders that lead to swallowing difficulty. Malnutrition and critical illness can lead to deconditioning and atrophy which can cause dysphagia, which in turn can lead to further malnutrition and deconditioning.

Circadian misalignment proxies, BMI, and chronic conditions: the role for weekday to weekend sleep differences.

OBJECTIVE: To evaluate whether social jet lag (SJL) and weekend catch-up sleep (CUS), proxies of circadian misalignment, were associated with BMI and chronic conditions. METHODS: Participants (n = 2,050,18-65y) were part of a virtual cross-sectional and population-based research. We examined CUS and SJL as continuous and categorical (< 1 h,1-2 h, > 2 h). Linear regression analyses were performed to assess the differences in BMI (outcome) associated with CUS and SJL. Restricted cubic splines were performed to explore the shape of the relationship between weekday-to-weekend variability in sleep duration, midpoint, wake time, and bedtime. Logistic regression models were used to estimate ORs(95%CIs) for chronic conditions and overweight related to CUS and SJL. Analyses were adjusted for sleep duration, biological and behavior-related variables. RESULTS: We found a positive association of SJL and CUS with BMI. The effects remained even after adjustment for weekly sleep duration and demonstrated a proportional increase with the magnitude of sleep variability. Among participants with SJL > 2 h, BMI increased by 2.29 kg/m2 (95%CI:0.84;3.74,p:0.002). They also had 129% higher odds of chronic conditions (95%CI:1.16;4.52, p:0.01) and 119% higher odds of overweight (95%CI: 1.20;3.98,p:0.01). Individuals with CUS > 2 h presented 78% higher odds of overweight (95%CI:1.27;2.50,p:0.001) and an increase of 1.61 kg/m2 in BMI (95%CI: 0.81; 2.40,p < 0.001). CONCLUSIONS: Our findings, which demonstrate that even a slight weekend sleep extension and variability of just 1 h is associated with higher values of BMI, suggest incorporating measures for sleep consistency and regularity into clinical protocols and public health guidelines to prevent and treat obesity and related diseases.

Metabolic outcomes in obese mice undergoing one-anastomosis gastric bypass (OAGB) with a long or a short biliopancreatic limb.

One-anastomosis gastric bypass (OAGB) has gained importance as a safe and effective operation to treat morbid obesity. It is not known whether a long biliopancreatic limb (BPL) in OAGB surgery compared to a short BPL results in beneficial metabolic outcomes. 5-week-old male C57BL/6J mice fed a high-fat diet for 8 weeks underwent OAGB surgery with defined short and long BPL lengths, or sham surgery combined with caloric restriction. Weight loss, glucose tolerance, obesity-related comorbidities, endocrine effects, gut microbiota and bile acids were assessed. Total weight loss was independent of the length of the BPL after OAGB surgery. However, a long BPL was associated with lower glucose-stimulated insulin on day 14, and an improved glucose tolerance on day 35 after surgery. A long BPL resulted in reduced total cholesterol. There were no differences in the resolution of metabolic dysfunction-associated steatotic liver disease and adipose tissue inflammation. Tendencies of an attenuated hypothalamic-pituitary-adrenal axis and aldosterone were present in the long BPL group. In OAGB-operated mice, we found an increase in primary conjugated bile acids (pronounced in long BPL) along with a loss in bacterial Desulfovibrionaceae and Erysipelotrichaceae and simultaneous increase in Akkermansiaceae, Sutterellaceae and Enterobacteriaceae. In sum, OAGB surgery with a long compared to a short BPL led to similar weight loss, but improved glucose metabolism, lipid and endocrine outcomes in obese mice, potentially mediated through changes in gut microbiota and related bile acids. Tailoring the BPL length in humans might help to optimize metabolic outcomes after bariatric surgery.

Re-evaluating the relationship between youth with HIV and BMI in an age of increasing rates of overweight and obese youth.

BACKGROUND: Newer antiretrivirals (ART) have shifted the metabolic experiences of people with HIV (PWH) from those of wasting syndrome to increases in body mass index (BMI). This study sought to examine the relationship between BMI and ART use among youth with HIV (YWH). METHODS: Charts from YWH ages 10-24 with at least two documented BMIs at least 6 months apart between 2017 and 2020 were included (N = 44). Statistical analyses were conducted in SAS 9.4. RESULTS: Clients were predominately African American (66%) males (73%) aged 19-24 years (64%), with men having sex with men (48%) being the most common mode of transmission. YWH on non-integrase inhibitor (INSTI) regimens had greater absolute increases in BMI compared to those on INSTI regimens (p = 0.03). Fourteen percent of clients using INSTI experienced an increase in BMI class from normal to overweight or overweight to obese; no non-INSTI users changed BMI class. Time since diagnosis and BMI change due to weight gain were positively associated (p = 0.03) among behaviorally-acquired YWH. CONCLUSIONS: Increasing BMI and changing BMI classes may be more likely among YWH using INSTI. More longitudinal studies inclusive of diet and exercise profiles are needed to understand the relationship between INSTI and YWH BMI.

Adipose exosomal noncoding RNAs: Roles and mechanisms in metabolic diseases.

Exosomes are extracellular vesicles, measuring 40-160 nm in diameter, that are released by many cell types and tissues, including adipose tissue. Exosomes are critical mediators of intercellular communication and their contents are complex and diverse. In recent years, accumulating evidence has proved that multiple adipose tissue-derived exosomal noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in the pathogenesis of diverse metabolic diseases, such as obesity. In this narrative review, we focus on the adipose tissue-derived exosomal ncRNAs, especially exosomal miRNAs, and their dysregulation in multiple types of metabolic diseases. A deeper understanding of the role of adipose tissue-derived exosomal ncRNAs may help provide new diagnostic and treatment methods for metabolic diseases.

Abnormal biochemical indicators of neonatal inherited metabolic disease in carriers.

BACKGROUND: Traditional biochemical screening for neonatal inherited metabolic diseases has high false-positive rates and low positive predictive values, which are not conducive to early diagnosis and increase parents' anxiety. This study analysed the relationship between gene variant carriers and their biochemical indicators in traditional biochemical screening, aiming to find explanations for false positives in newborns. RESULTS: This retrospective study included 962 newborns. Newborns underwent traditional biochemical screening at birth using blood staining and genomic sequencing of their stored blood staining using the NeoSeq Pro panel, which was able to detect 154 pathogenic genes and 86 diseases. A total of 632 newborns were carriers of gene variants. 56% of congenital hypothyroidism carriers had higher thyroid-stimulating hormone levels than normal newborns. Abnormal biochemical indices were detected in 71% of carriers of organic acid metabolic diseases, 69% of carriers of amino acid metabolic diseases, and 85% of carriers of fatty acid ß oxidation disorders. In carriers associated with organic acid metabolic diseases, the propionylcarnitine (C3), C3/acetylcarnitine (C2), and methylmalonylcarnitine (C4DC) + 3-hydroxyisovalerylcarnitine (C5OH) levels were higher than those in non-carriers (C3: 4.12 vs. 1.66 µmol/L; C3/C2: 0.15 vs. 0.09; C4DC + C5OH: 0.22 vs. 0.19 µmol/L). In carriers associated with amino acid metabolic diseases, phenylalanine levels were higher than those in non-carriers (68.00 vs. 52.05 µmol/L). For carriers of fatty acid ß oxidation disorders, butyrylcarnitine levels were higher than those in non-carriers (0.31 vs. 0.21 µmol/L), while the free carnitine levels were lower than those in non-carriers (14.65 vs. 21.87 µmol/L). There was a higher occurrence of carriers among newborns who received false-positive results for amino acid metabolic diseases compared to those who received negative results (15.52% vs. 6.71%). Similarly, there was a higher occurrence of carriers among newborns who received false-positive results for fatty acid ß oxidation disorders compared to those who received negative results (28.30% vs. 7.29%). CONCLUSIONS: This study showed that the carriers comprised a large number of newborns. Carriers had abnormal biochemical indicators compared with non-carriers, which could explain the false-positive rate for newborns using traditional newborn biochemical screening, especially in amino acid metabolic and fatty acid ß oxidation disorders.

The Degree of Inulin Polymerization Is Important for Short-Term Amelioration of High-Fat Diet (HFD)-Induced Metabolic Dysfunction and Gut Microbiota Dysbiosis in Rats.

Inulin, a non-digestible polysaccharide, has gained attention for its prebiotic properties, particularly in the context of obesity, a condition increasingly understood as a systemic inflammatory state linked to gut microbiota composition. This study investigates the short-term protective effects of inulin with different degrees of polymerization (DPn) against metabolic health deterioration and gut microbiota alterations induced by a high-fat diet (HFD) in Sprague Dawley rats. Inulin treatments with an average DPn of 7, 14, and 27 were administered at 1 g/kg of bodyweight to HFD-fed rats over 21 days. Body weight, systemic glucose levels, and proinflammatory markers were measured to assess metabolic health. Gut microbiota composition was analyzed through 16S rRNA gene sequencing. The results showed that inulin27 significantly reduced total weight gain and systemic glucose levels, suggesting a DPn-specific effect on metabolic health. The study also observed shifts in gut microbial populations, with inulin7 promoting several beneficial taxa from the Bifidobacterium genera, whilst inducing a unique microbial composition compared to medium-chain (DPn 14) and long-chain inulin (DPn: 27). However, the impact of inulin on proinflammatory markers and lipid metabolism parameters was not statistically significant, possibly due to the short study duration. Inulin with a higher DPn has a more pronounced effect on mitigating HFD-induced metabolic health deterioration, whilst inulin7 is particularly effective at inducing healthy microbial shifts. These findings highlight the benefits of inulin as a dietary adjuvant in obesity management and the importance of DPn in optimizing performance.

The Obese Taste Bud study: Objectives and study design.

AIMS: Taste modifies eating behaviour, impacting body weight and potentially obesity development. The Obese Taste Bud (OTB) Study is a prospective cohort study launched in 2020 at the University of Leipzig Obesity Centre in cooperation with the HI-MAG Institute. OTB will test the hypothesis that taste cell homeostasis and taste perception are linked to obesity. Here, we provide the study design, data collection process and baseline characteristics. MATERIALS AND METHODS: Participants presenting overweight, obesity or normal weight undergo taste and smell tests, anthropometric, and taste bud density (TBD) assessment on Day 1. Information on physical and mental health, eating behaviour, physical activity, and dental hygiene are obtained, while biomaterial (saliva, tongue swap, blood) is collected in the fasted state. Further blood samples are taken during a glucose tolerance test. A stool sample is collected at home prior to Day 2, on which a taste bud biopsy follows dental examination. A subsample undergoes functional magnetic resonance imaging while exposed to eating-related cognitive tasks. Follow-up investigations after conventional weight loss interventions and bariatric surgery will be included. RESULTS: Initial results show that glycated haemoglobin levels and age are negatively associated with TBD, while an unfavourable metabolic profile, current dieting, and vegan diet are related to taste perception. Olfactory function negatively correlates with age and high-density lipoprotein cholesterol. CONCLUSION: Initial findings suggest that metabolic alterations are relevant for taste and smell function and TBD. By combining omics data from collected biomaterial with physiological, metabolic and psychological data related to taste perception and eating behaviour, the OTB study aims to strengthen our understanding of taste perception in obesity.

Low-frequency electrically induced exercise after spinal cord injury: Physiologic challenge to skeletal muscle and feasibility for long-term use.

CONTEXT: Skeletal muscle has traditionally been considered a "force generator": necessary for purposes of locomotion, but expendable for non-ambulators who use wheelchairs, such as people with a spinal cord injury (SCI). Active skeletal muscle plays an indispensable role in regulating systemic metabolic functions, even in people with paralysis, but because of severe osteoporosis, high tetanic muscle forces induced with high frequency electrical stimulation may be risky for some individuals. The purpose of this study was to compare the physiologic muscle properties incurred by two low force/low frequency repetitive stimulation protocols (1 and 3 Hz); and, to assess the acceptability of each protocol among people with SCI. METHODS: Ten individuals with chronic SCI (12.9 years) and 11 individuals without SCI (NonSCI) participated in the study. Participants received either 1 or 3 Hz stimulation to the quadriceps muscle on Day 1, then the converse on Day 2. Each session consisted of 1000 stimulus pulses. RESULTS: The initial and maximum forces were similar for the 1 and 3 Hz frequencies. The fatigue index (FI) for SCI and NonSCI groups were lower (P < 0.007) for 3 Hz than for 1 Hz (0.34 ± 0.17 versus 0.65 ± 0.16 and 0.72 ± 0.14 versus 0.87 ± 0.07, respectively). CONCLUSION: The 3 Hz stimulation offered the greatest physiological challenge and was perceived as more acceptable for long term use among people with SCI.

Advances in fecal microbiota transplantation for the treatment of diabetes mellitus.

Diabetes mellitus (DM) refers to a group of chronic diseases with global prevalence, characterized by persistent hyperglycemia resulting from various etiologies. DM can harm various organ systems and lead to acute or chronic complications, which severely endanger human well-being. Traditional treatment mainly involves controlling blood sugar levels through replacement therapy with drugs and insulin; however, some patients still find a satisfactory curative effect difficult to achieve. Extensive research has demonstrated a close correlation between enteric dysbacteriosis and the pathogenesis of various types of DM, paving the way for novel therapeutic approaches targeting the gut microbiota to manage DM. Fecal microbiota transplantation (FMT), a method for re-establishing the intestinal microbiome balance, offers new possibilities for treating diabetes. This article provides a comprehensive review of the correlation between DM and the gut microbiota, as well as the current advancements in FMT treatment for DM, using FMT as an illustrative example. This study aims to offer novel perspectives and establish a theoretical foundation for the clinical diagnosis and management of DM.

Non-significant influence between aerobic and anaerobic sample transport materials on gut (fecal) microbiota in healthy and fat-metabolic disorder Thai adults.

Background: The appropriate sample handling for human fecal microbiota studies is essential to prevent changes in bacterial composition and quantities that could lead to misinterpretation of the data. Methods: This study firstly identified the potential effect of aerobic and anaerobic fecal sample collection and transport materials on microbiota and quantitative microbiota in healthy and fat-metabolic disorder Thai adults aged 23-43 years. We employed metagenomics followed by 16S rRNA gene sequencing and 16S rRNA gene qPCR, to analyze taxonomic composition, alpha diversity, beta diversity, bacterial quantification, Pearson's correlation with clinical factors for fat-metabolic disorder, and the microbial community and species potential metabolic functions. Results: Our study successfully obtained microbiota results in percent and quantitative compositions. Each sample exhibited quality sequences with a >99% Good's coverage index, and a relatively plateau rarefaction curve. Alpha diversity indices showed no statistical difference in percent and quantitative microbiota OTU richness and evenness, between aerobic and anaerobic sample transport materials. Obligate and facultative anaerobic species were analyzed and no statistical difference was observed. Supportively, the beta diversity analysis by non-metric multidimensional scale (NMDS) constructed using various beta diversity coefficients showed resembling microbiota community structures between aerobic and anaerobic sample transport groups (P = 0.86). On the other hand, the beta diversity could distinguish microbiota community structures between healthy and fat-metabolic disorder groups (P = 0.02), along with Pearson's correlated clinical parameters (i.e., age, liver stiffness, GGT, BMI, and TC), the significantly associated bacterial species and their microbial metabolic functions. For example, genera such as Ruminococcus and Bifidobacterium in healthy human gut provide functions in metabolisms of cofactors and vitamins, biosynthesis of secondary metabolites against gut pathogens, energy metabolisms, digestive system, and carbohydrate metabolism. These microbial functional characteristics were also predicted as healthy individual biomarkers by LEfSe scores. In conclusion, this study demonstrated that aerobic sample collection and transport (<48 h) did not statistically affect the microbiota and quantitative microbiota analyses in alpha and beta diversity measurements. The study also showed that the short-term aerobic sample collection and transport still allowed fecal microbiota differentiation between healthy and fat-metabolic disorder subjects, similar to anaerobic sample collection and transport. The core microbiota were analyzed, and the findings were consistent. Moreover, the microbiota-related metabolic potentials and bacterial species biomarkers in healthy and fat-metabolic disorder were suggested with statistical bioinformatics (i.e., Bacteroides plebeius).

Recurrent familial case of early childhood sudden death: Complex post mortem genetic investigations.

INTRODUCTION: Sudden Unexplained Death in Childhood (SUDC) needs to be fully assessed considering its impact on the family, parents and siblings. Inborn Errors of Metabolism (IEM) such as Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) should be taken into consideration when SUDC occurres. Our aim is to present a family with two successive SUDC and to discuss the post-mortem genetics investigations revealing an IEM implication. CASES REPORT: A complete autopsy with genetic testing was performed when the proband, a 4-year-old girl, died. A few years previously, her older brother had died at the same age and off the same condition. Years later, his exhumation was necessary in order to perform a post-mortem diagnosis.The two siblings were revealed to have had the same pathogenic genotype of the ACADM gene, heterozygous substitutions in ACADM (NM_000016.5): c.985 A>G p.(Lys329Glu) and c.347 G>A p.(Cys116Tyr). In addition, they also both carried a VUS in TECRL, a gene implicated in Catecholaminergic Polymorphic Tachycardia Ventricular (CPVT) and SUDC. CONCLUSION: We illustrate the importance of exome analyses for investigating unexplained sudden death, especially in children, with the possible impact for genetic counselling in the family. The finding of the implication of ACADM gene in this case, raises likely responsibility of the public health system in countries such as France, who delayed implementation of new born screening for these conditions. Exome analyses in this case detected unexpected complexity in interpretation linked to the identification of a second candidate gene for SUDC.

Benefit-Risk Assessment of ChatGPT Applications in the Field of Diabetes and Metabolic Illnesses: A Qualitative Study.

Background: The use of ChatGPT and artificial intelligence (AI) in the management of metabolic and endocrine disorders presents both significant opportunities and notable risks. Objectives: To investigate the benefits and risks associated with the application of ChatGPT in managing diabetes and metabolic illnesses by exploring the perspectives of endocrinologists and diabetologists. Methods and materials: The study employed a qualitative research approach. A semi-structured in-depth interview guide was developed. A convenience sample of 25 endocrinologists and diabetologists was enrolled and interviewed. All interviews were audiotaped and verbatim transcribed; then, thematic analysis was used to determine the themes in the data. Results: The findings of the thematic analysis resulted in 19 codes and 9 major themes regarding the benefits of implementing AI and ChatGPT in managing diabetes and metabolic illnesses. Moreover, the extracted risks of implementing AI and ChatGPT in managing diabetes and metabolic illnesses were categorized into 7 themes and 14 codes. The benefits of heightened diagnostic precision, tailored treatment, and efficient resource utilization have potential to improve patient results. Concurrently, the identification of potential challenges, such as data security concerns and the need for AI that can be explained, enables stakeholders to proactively tackle these issues. Conclusions: Regulatory frameworks must evolve to keep pace with the rapid adoption of AI in healthcare. Sustained attention to ethical considerations, including obtaining patient consent, safeguarding data privacy, ensuring accountability, and promoting fairness, remains critical. Despite its potential impact on the human aspect of healthcare, AI will remain an integral component of patient-centered care. Striking a balance between AI-assisted decision-making and human expertise is essential to uphold trust and provide comprehensive patient care.

Regulatory frameworks must evolve to keep pace with the rapid adoption of AI in healthcare. Sustained attention to ethical considerations, including obtaining patient consent, safeguarding data privacy, ensuring accountability, and promoting fairness, remains critical. Despite its potential impact on the human aspect of healthcare, AI will remain an integral component of patient-centered care. The use of ChatGPT in the management of metabolic and endocrine disorders presents both significant opportunities and notable risks. The benefits of heightened diagnostic precision, tailored treatment, and efficient resource utilization have potential to improve patient results. Concurrently, the identification of potential challenges, such as data security concerns and the need for AI that can be explained, enables stakeholders to proactively tackle these issues. Regulatory frameworks must evolve to keep pace with the rapid adoption of AI in healthcare. Sustained attention to ethical considerations, including obtaining patient consent, safeguarding data privacy, ensuring accountability, and promoting fairness, remains critical. Despite its potential impact on the human aspect of healthcare, AI will remain an integral component of patient-centered care. Striking a balance between AI-assisted decision-making and human expertise is essential to uphold trust and provide comprehensive patient care.

A view on the skin-bone axis: unraveling similarities and potential of crosstalk.

The phrase "skin as a mirror of internal medicine," which means that the skin reflects many of the diseases of the internal organs, is a well-known notion. Despite the phenotypic differences between the soft skin and hard bone, the skin and bone are highly associated. Skin and bone consist of fibroblasts and osteoblasts, respectively, which secrete collagen and are involved in synthesis, while Langerhans cells and osteoclasts control turnover. Moreover, the quality and quantity of collagen in the skin and bone may be modified by aging, inflammation, estrogen, diabetes, and glucocorticoids. Skin and bone collagen are pathologically modified by aging, drugs, and metabolic diseases, such as diabetes. The structural similarities between the skin and bone and the crosstalk controlling their mutual pathological effects have led to the advocacy of the skin-bone axis. Thus, the skin may mirror the health of the bones and conversely, the condition of the skin may be reflected in the bones. From the perspective of the skin-bone axis, the similarities between skin and bone anatomy, function, and pathology, as well as the crosstalk between the two, are discussed in this review. A thorough elucidation of the pathways governing the skin-bone axis crosstalk would enhance our understanding of disease pathophysiology, facilitating the development of new diagnostics and therapies for skin collagen-induced bone disease and of new osteoporosis diagnostics and therapies that enhance skin collagen to increase bone quality and density.

Preterm birth: A neuroinflammatory origin for metabolic diseases?

Preterm birth and its related complications have become more and more common as neonatal medicine advances. The concept of "developmental origins of health and disease" has raised awareness of adverse perinatal events in the development of diseases later in life. To explore this concept, we propose that encephalopathy of prematurity (EoP) as a potential pro-inflammatory early life event becomes a novel risk factor for metabolic diseases in children/adolescents and adulthood. Here, we review epidemiological evidence that links preterm birth to metabolic diseases and discuss possible synergic roles of preterm birth and neuroinflammation from EoP in the development of metabolic diseases. In addition, we explore theoretical underlying mechanisms regarding developmental programming of the energy control system and HPA axis.

Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice.

Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation, known as meta-inflammation. This state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver disease. Pyruvate is a glycolytic metabolite and a crucial node in various metabolic pathways. However, its role and molecular mechanism in obesity and associated complications are obscure. In this study, we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain, white adipose tissue inflammation, and metabolic dysregulation. To identify the target proteins of pyruvate, drug affinity responsive target stability was employed with proteomics, cellular thermal shift assay, and isothermal drug response to detect the interactions between pyruvate and its molecular targets. Consequently, we identified cytosolic phospholipase A2 (cPLA2) as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity, white adipose tissue inflammation, and hepatic steatosis in a cPLA2-dependent manner. Studies with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated, confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and obesity. Overall, our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity, but it also sheds light on the mechanism of its action. Pyruvate's prior clinical use indicates that it can be considered a safe and viable alternative for obesity, whether consumed as a dietary supplement or as part of a regular diet.