Application of 3-hydroxycapryloyl carnitine as target spot of metabolic liver disease after cholecystectomy

Abstract

The invention provides an application of 3-hydroxyl capryloyl carnitine as a target spot of metabolic liver diseases after cholecystectomy. Through Mendel randomization and mediation analysis of two samples, it is confirmed for the first time that 3-hydroxycapryloyl carnitine is a key causal mediating factor for risk increase of MASLD caused by cholecystectomy, and the mediating proportion is 10.37%. It is directly proved that the disease progress can be affected by intervening the metabolite level.

Description

Technical Field

[0001] This invention belongs to the field of biological diagnostics and pharmaceutical technology, specifically relating to the application of 3-hydroxyoctanoylcarnitine as a target for metabolic liver disease after cholecystectomy. Background Technology

[0002] Cholecystectomy, the surgical removal of the gallbladder, remains the standard treatment for gallbladder disease. As one of the most frequently performed surgical procedures globally, it was previously considered safe and without serious long-term consequences. However, new evidence suggests that cholecystectomy is associated with an increased risk of abnormalities, particularly fatty liver disease associated with metabolic dysfunction (MASLD; formerly known as non-alcoholic fatty liver disease or NAFLD).

[0003] MASLD is a chronic, progressive liver disease characterized by excessive lipid accumulation in the liver without heavy alcohol consumption. It is often associated with metabolic syndrome, including obesity, type 2 diabetes, hypertension, and dyslipidemia. MASLD affects nearly one-third of the world's population, constituting a significant public health burden. The disease can progress to metabolically dysfunction-associated fatty liver disease (MASH), which can lead to fibrosis, cirrhosis, and ultimately liver cancer, further exacerbating its global impact. Two cross-sectional studies have reported an increased risk of MASLD after cholecystectomy. A large longitudinal cohort study involving 18,656 Korean adults showed that cholecystectomy was associated with a 1.48-fold increased risk of MASLD. Consistent with this, a systematic review and meta-analysis of 20 observational studies involving 27.3 million participants revealed a 63% increased overall risk of liver disease after cholecystectomy, with particularly elevated risks of non-alcoholic fatty liver disease (54%), cirrhosis (173%), and primary cirrhosis (46%).

[0004] There is a clear association between cholecystectomy and an increased risk of long-term metastatic angina pectoris (MASLD) after the procedure, but its specific pathogenesis remains unclear, resulting in a lack of targeted prevention and treatment methods in clinical practice. Existing MASLD management programs (such as lifestyle interventions and insulin sensitizers) do not target the metabolic pathway disorders caused by the specific cause of cholecystectomy, and their efficacy is limited and they have side effects.

[0005] Currently, clinical interventions for MASLD are mainly based on its broad metabolic abnormalities rather than specific etiologies, and primarily include the following treatment methods: 1. First-line treatment: Lifestyle intervention (weight loss, dietary adjustments). This method is universally applicable but relies on long-term patient adherence and is not very effective in addressing specific postoperative metabolic disorders.

[0006] 2. Drug treatment: such as pioglitazone (to improve insulin resistance), vitamin E (antioxidant), and obeticholic acid (to regulate bile acid metabolism). These drugs act on downstream or bypass pathways in the pathogenesis of MASLD, rather than targeting the unique pathophysiological process caused by cholecystectomy, and have side effects such as weight gain and skin itching.

[0007] 3. Surgical management: Current clinical guidelines only focus on perioperative safety and short-term complications of cholecystectomy. There are no standard monitoring and prevention protocols for long-term metabolic sequelae (such as MASLD) caused by cholecystectomy, and no specific targeted drugs.

[0008] The above treatment methods have the following drawbacks. 1. Unknown cause and blind treatment: Current methods do not target the newly discovered causal chain of "cholecystectomy → specific metabolite disorder → liver damage", and are symptomatic treatments that fail to block the disease from its root cause.

[0009] 2. Lack of early prevention targets: The inability to identify modifiable biochemical mediators that directly lead to MASLD in the early postoperative period results in missed opportunities for prevention.

[0010] 3. Drug nonspecificity: Existing drugs may be effective for postoperative MASLD, but due to their non-targeting nature, the efficacy / risk is relatively low.

[0011] Therefore, there is an urgent clinical need to clarify the specific pathogenic mechanism of postoperative MASLD and develop targeted intervention strategies accordingly. Summary of the Invention

[0012] To address the aforementioned issues, this invention provides the application of 3-hydroxyoctanoylcarnitine as a target for metabolic liver disease after cholecystectomy.

[0013] This invention provides a treatment approach of "reducing 3-hydroxyoctanoylcarnitine levels." Based on this core principle, various alternative intervention methods can be employed: 1. Alternative Targets: In addition to directly targeting the 3-hydroxycaprylcarnitine molecule itself, it is also possible to target its upstream regulators. For example, protecting the use of a compound that inhibits the production of its precursor (such as caprylyl-CoA) or promotes its diversion to other pathways in the same disease. This is also to achieve the ultimate goal of reducing 3-hydroxycaprylcarnitine levels.

[0014] 2. Combination therapy: Although this study focuses on a single target, drugs that primarily reduce 3-hydroxyoctanoylcarnitine can be combined with a drug with a complementary mechanism of action (such as a hepatoprotective drug or an anti-inflammatory drug) to form a fixed-dose combination preparation to enhance efficacy or reduce side effects. This approach should also be considered an extension of the present invention.

[0015] The technical solution of this invention is: the application of substances that detect 3-hydroxyoctanoylcarnitine in the preparation of products for the diagnosis of metabolic liver diseases after cholecystectomy.

[0016] Furthermore, the substance is a reagent for detecting the content of 3-hydroxyoctanoylcarnitine.

[0017] A kit for the auxiliary diagnosis of metabolic liver disease after cholecystectomy, comprising a reagent for detecting 3-hydroxyoctanoylcarnitine.

[0018] Application of active substances that lower the level of 3-hydroxyoctanoylcarnitine in the body in the preparation of drugs for the prevention or treatment of metabolic liver disease after cholecystectomy.

[0019] Furthermore, the drug may be a small molecule inhibitor, adsorbent, metabolism promoter, or biological agent.

[0020] Furthermore, the small molecule inhibitor refers to a compound that specifically inhibits the key enzyme that catalyzes the formation of 3-hydroxyoctanoylcarnitine.

[0021] Furthermore, the adsorbent refers to a molecule that can specifically bind to and remove 3-hydroxyoctanoylcarnitine in the intestine or blood.

[0022] Furthermore, the metabolic promoter refers to a compound that activates the enzymatic pathway that further metabolizes 3-hydroxyoctanoylcarnitine.

[0023] Furthermore, the biological agent refers to a monoclonal antibody or fragment thereof that specifically targets and neutralizes 3-hydroxyoctanoylcarnitine.

[0024] This invention, through two-sample Mendelian randomization and mediation analysis, is the first to demonstrate that 3-hydroxyoctanoylcarnitine is a key causal mediator of increased MASLD risk following cholecystectomy (mediation rate 10.37%). This directly proves that intervention in the level of this metabolite can affect disease progression. Specifically, cholecystectomy can significantly increase the level of 3-hydroxyoctanoylcarnitine (…). β = 0.933, 95% CI: 0.356-1.510, FDR = 0.043), and elevated levels of this metabolite were positively correlated with the risk of metabolic dysfunction-associated fatty liver disease (MASLD). β = 0.257, 95% CI: 0.126–0.389, FDR = 0.002). Therefore, 3-hydroxyoctanoylcarnitine played a significant positive mediating role, accounting for 10.37% of the total causal effect of cholecystectomy on MASLD (mediation effect β = 0.241, 95% CI: 0.044–0.438, FDR = 0.017, mediation proportion: 10.37%).Figure 10 ).

[0025] The beneficial effects of this invention are: 1. Causal targeting with a clear mechanism: For the first time, the causal metabolite linking cholecystectomy and MASLD has been identified and validated. Intervening in this target can directly interrupt the clearly defined pathogenic pathway, theoretically achieving etiological treatment with more precise and fundamental expected efficacy.

[0026] 2. A novel therapeutic target for liver disease associated with specific surgical procedures has been discovered, providing a theoretical basis and clear direction for drug development.

[0027] 3. Combining prevention and treatment: This target offers the possibility of early drug prevention for high-risk groups after cholecystectomy, reducing risk mediators before liver damage occurs, while also providing new treatment options for those already suffering from the disease. Attached Figure Description

[0028] Figure 1 The diagram shown is a schematic of the technical route; Figure 2 The results shown are from Mendel randomization. Figure 3 The image shows the changes in blood metabolite profiles after cholecystectomy. Figure 4 The figure shown is a scatter plot of the MR estimate of the risk of MASLD after cholecystectomy. Figure 5 The figure shown is a scatter plot of the MR estimate of the risk of 3-hydroxyoctanoylcarnitine after cholecystectomy. Figure 6 The diagram shown is a funnel plot representing the MR estimate of the risk of MASLD after cholecystectomy. Figure 7 The figure shown is a funnel diagram of MR estimation of 3-hydroxyoctanoylcarnitine after cholecystectomy; Figure 8 The figure shows a leave-one-out analysis of the MR estimation of the risk of MASLD after cholecystectomy. Figure 9 The image shows a leave-one-out analysis of MR estimation for 3-hydroxyoctanoylcarnitine following cholecystectomy. Figure 10 The figure shows the risk of MASLD associated with 3-hydroxyoctanoylcarnitine-mediated cholecystectomy. Detailed Implementation To make the objectives, steps, and advantages of the embodiments of the present invention clearer, the steps of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the protection scope of the present invention.

[0029] Unless otherwise specified, the technical terms used in the following embodiments have the same meaning as commonly understood by those skilled in the art, and the raw materials used in the following embodiments, unless otherwise specified, are all commercially available.

[0030] Example 1 This study used a two-sample Mendelian randomization method to assess the impact of cholecystectomy on the risk of MASLD and the blood metabolite profile, and elucidated its underlying biological mechanisms through comprehensive functional enrichment analysis. Simultaneously, mediation analysis was combined to verify the mediating role of metabolites in the relationship between cholecystectomy and the risk of MASLD.

[0031] I. Materials and Methods 1. Data Source Figure 1 An overview diagram of the study design is shown. Pooled statistics are from the Genome-wide Association Study (GWAS) of European ancestry. Pooled GWAS statistics for cholecystectomy (18,319 cases and 444,614 controls) and MASLD (4,761 cases and 373,227 controls) are from the IEU Open GWAS (https: / / gwas.mrcieu.ac.uk / ), access numbers ukb-b-6235 and ebi-a-ST90054782, respectively. Pooled GWAS statistics for a total of 1,091 blood metabolites and 309 metabolite ratios are from the GWAS Directory (https: / / www.ebi.ac.uk / gwas / ), access number GCST90199621-9020100. See Table 1 for details.

[0032] Table 1 Summary Statistics of GWAS

[0033] 2. IVs (Instrumental Variables) Screening This study employed the following steps to screen eligible instrumental variables for each exposure factor (Figure 1). First, single nucleotide polymorphisms (SNPs) that showed significant genome-wide association with the exposure factor were selected, with a screening threshold of [insert threshold here]. P <5×10 -8Secondly, SNPs were isolated based on linkage disequilibrium (LD), using a window size of 10,000 kb and r² < 0.001 to remove highly correlated sites, ensuring independence between instrumental variables. Thirdly, through calculation... F Statistical assessment of instrumental variable strength, retaining only F SNPs with a value >10 were selected to reduce bias from weak instrumental variables. Subsequently, effect allele alignment was performed on the exposure and outcome datasets to ensure that the allele orientation was consistent with the effect estimates. Finally, the MR Steiger test was used to validate the causal orientation of each instrumental variable, retaining only SNPs consistent with the prior causal orientation for subsequent analysis.

[0034] 3. Primary Mendelian Randomization (MR) Analysis This study employed a two-sample Mendelian randomization framework to assess the causal effects of cholecystectomy on blood metabolites (abundance and proportion) and the risk of MASLD (Figure 1). The main analysis used inverse variance weighted (IVW): first, Wald ratio estimates were calculated based on each instrumental variable, and then the overall causal effect was obtained through random effects integration. IVW provides unbiased and statistically efficient effect estimates when all instrumental variables meet the validity assumptions. Associations with a false discovery rate (FDR) below 0.05 were retained for subsequent analyses. To validate the robustness of the main results and control for pleiotropic effects, several supplementary methods were used for sensitivity analysis, including MR-PRESSO, weighted median, MR-Egger, and maximum likelihood. These methods, based on different pleiotropic assumptions, can identify outliers from multiple perspectives, reduce bias, and provide complementary evidence for causal inference.

[0035] 4. Sensitivity Analysis To control for potential level pleiotropic bias, this study used MR Egger's intercept test and MR The PRESSO algorithm is used for pleiotropic evaluation. Egger regression quantifies the average pleiotropic effect of instrumental variables through the intercept term and obtains a causal estimate after adjusting for pleiotropic effects based on the slope coefficient. MR Presso first conducts a global pleiotropic test using regression residuals. If significantly influential outliers are detected, they are removed, and the corrected causal estimate is recalculated. To further verify the reliability of the causal inference direction, the MR Steiger test is used for directionality verification. A test result of "TRUE" indicates that the observed causal direction is consistent with the prior hypothesis. Simultaneously, a leave-one-out method is performed. one Sensitivity analysis (SNP) was performed to determine whether the main analysis results were driven by a single instrumental variable. This analysis involved refitting the model after each SNP was removed sequentially, and comparing the successive effect sizes with the total effect size based on all instrumental variables. If a significant change in effect size occurred after removing a particular SNP, it suggested that the variant might be a high-impact site, requiring a thorough assessment of its sensitivity and reliability.

[0036] 5. Enrichment Analysis Metabolite enrichment analysis was performed using MetaboAnalyst 6.0 (https: / / www.metaboanalyst.ca / ) and the Metabolomics Pathway Relationship Database (MP-DB), which integrates 3,694 metabolites and lipid pathways from KEGG, HMDB, Reactome, and WikiPathways.

[0037] 6. Mediation Analysis We employed a two-step Mendelian randomization design to investigate whether blood metabolites play a potential mediating role in the causal pathway from cholecystectomy to MASLD (Figure 1). This design decomposed the total causal effect of cholecystectomy on MASLD into two parts: (1) the direct effect (denoted as C' in Figure 1), representing the independent effect without the mediating variable being tested; and (2) the indirect (mediating) effect (denoted as A×B in Figure 1), i.e., the causal pathway mediated by blood metabolites. We further calculated the contribution of each mediating variable to the total effect. The standard error (SE) and 95% confidence interval (CI) of the mediating effect were estimated using Monte Carlo simulation with 10,000 repeated iterations.

[0038] 7. Statistical Analysis All statistical analyses were performed in the R language environment (version 4.2.2). The R packages used in this study and their corresponding analyses are as follows: MR-PRESSO (version 1.0) was used to detect and correct for level pleiotropy; TwoSampleMR (version 0.5.8) was used to perform instrumental variable screening, main Mendelian randomization analysis, and sensitivity analysis; and RMadiation (version 1.22) was used to conduct mediation effect analysis. The results were visualized using the following packages: forestplot (version 3.1.1) for forest plots, ggplot2 (version 3.5.1) for lollipop plots, pheatmap (version 1.0.12) for heatmaps, and ggsankey (version 0.0.99999) for Sankey plots.

[0039] II. Results 1. Cholecystectomy increases the risk of MASLD. like Figure 2 As shown, inverse variance-weighted (IVW) analysis revealed a significant causal effect of cholecystectomy on the increased risk of MASLD. β :2.33; 95% CI: 0.23–4.42, P = 0.030; IVW). MR Egger intercept test did not detect significant level pleiotropy. P = 0.76, Table 2). Although the MR-PRESSO global test found one outlier (rs4665972, P <0.001, Table 3), but the corrected estimate after removing this site remained stable and consistent with the main analysis direction ( β :2.84; 95% CI: 1.23–4.45, P = 0.001), no substantial change occurred ( P =0.59 (Table 3). Sensitivity analysis showed that cholecystectomy had a significant causal association with the increased risk of MASLD, and the effect direction was highly consistent across multiple MR methods (IVW, MR-Egger, weighted median, and maximum likelihood) (Figure 4), indicating good robustness of the causal effect. The funnel plot showed an approximately symmetrical distribution, and no obvious effect bias was observed (Figure 6). Leave-one-out analysis showed that the effect estimate did not shift significantly after removing individual SNPs one by one, confirming that no single SNP dominated the result, further supporting the stability and reliability of the causal association (Figure 8). The MR Steiger test further confirmed the causal direction inferred in this study (Table 4).

[0040] Table 2 MR-egger intercept term test

[0041] Table 3 MR-PRESSO Test Results

[0042] Table 4. MR-Steiger Test Results

[0043] 2. Cholecystectomy alters the abundance of blood metabolites and disrupts the fatty acid β-oxidation pathway. Cholecystectomy significantly altered the abundance of 48 blood metabolites, with 31 upregulated and 17 downregulated. Figure 3A). The most significantly affected metabolite categories were lipids (27.08%, n=13), amino acids (25%, n=12), and xenobiotics (10.42%, n=5). The ratios of eight metabolites changed significantly, with five increasing and three decreasing. Figure 3 A). Notably, we observed multiple fatty acid β-types. Oxidation intermediates were significantly elevated, including butyrylcarnitine (C4) ( β =0.908; 95% CI: 0.353-1.464; FDR =0.041; IVW), isobutyrylcarnitine (C4) ( β =1.160; 95% CI: 0.500-1.821; FDR =0.029; IVW), cis-4-enoylcarnitine (C10:1) β =0.927; 95% CI: 0.349-1.502; FDR =0.044; IVW), 3-hydroxyoctanoylcarnitine ( β =0.933; 95% CI: 0.356-1.510; FDR =0.042; IVW). Consistent with this, it reflects β. The ratio of acetylcarnitine (C2) to propionylcarnitine (C3), an important marker of oxidation efficiency, was also significantly increased. β =0.909; 95% CI: 0.355-1.463; FDR =0.041; IVW). In addition, levels of two bile acids were significantly elevated: bile acids ( β :1.350; 95% CI: 0.676-2.025, FDR =0009;IVW) and taurine-β-methylglycine sterol acid ( β :1.643; 95% CI: 0.642-2.645, FDR =0.041; IVW) and its associated hepatobiliary detoxification metabolite bile acid glucuronic acid ( β :1.110; 95% CI: 0.617-1.602, FDR =0.002; IVW) was also significantly elevated after cholecystectomy. Pathway enrichment analysis based on the RaMP database further validated the above results. Figure 3 B) suggests that related metabolic alterations are significantly enriched in bile acid-related biological processes, including SLC-mediated transmembrane transport (B). P =1.31×10 -4 And the transport of bile salts and organic acids, metal ions and amine compounds. P=0.02).

[0044] 3.3 Mediating role of hydroxyoctanoylcarnitine in the MASLD pathway during cholecystectomy This study found 3 Hydroxycaprylyl carnitine plays a significant mediating role in the pathway by which cholecystectomy increases the risk of MASLD. Specifically, cholecystectomy can significantly increase the risk of MASLD. Hydroxycaprylyl carnitine levels (β=0.933; 95% CI: 0.356–1.510); FDR =0.043, Figure 2 The increase in the level of this metabolite in the blood had a significant causal effect on the increased risk of MASLD (β=0.257; 95% CI: 0.126–0.389). FDR =0.002, Figure 2 ). Mediation analysis shows that 3 Hydroxycaprylyl carnitine (2) played a significant positive mediating role in this pathway and made a significant contribution to the overall causal effect of increased MASLD risk caused by cholecystectomy (mediation effect β=0.241; 95% CI: 0.044–0.438; FDR=0.017; mediating proportion: 10.37%). Figure 10 Sensitivity analysis showed a significant positive causal association between cholecystectomy and elevated 3-hydroxycaprylyl carnitine levels. This association exhibited high consistency in effect direction across various MR methods (IVW, MR-Egger, weighted median, and maximum likelihood) (Figure 5), indicating good robustness of the causal effect. The funnel plot showed an approximately symmetrical distribution, with no obvious effect bias observed (Figure 7). Leave-one-out analysis showed no significant shift in effect estimation after eliminating individual SNPs, confirming that no single SNP dominated the result, further supporting the stability and reliability of the causal association (Figure 9). Both the MR-Egger intercept test (Table 2) and the MR-PRESSO test (Table 3) indicated that there was no significant level pleiotropic effect in the causal estimation of the risk of 3-hydroxycaprylyl carnitine occurrence by cholecystectomy in this study. The MR Steiger test (Table 4) further clarified the causal direction, verifying both the causal effect of cholecystectomy on 3-hydroxyoctanoylcarnitine levels and the causal effect of 3-hydroxyoctanoylcarnitine on the risk of MASLD, providing reliable directional evidence for the research conclusions.

[0045] III. Conclusion Cholecystectomy is one of the most common abdominal surgeries worldwide, and its long-term safety has once again become a focus of research and evaluation in recent years. Increasing evidence suggests a close association between this surgery and an increased risk of metabolic diseases, including metabolic-associated fatty liver disease (MASLD). However, the causal relationship between the two remains unclear, and the underlying mechanisms require further investigation. This study, through Mendelian randomization (MR) analysis, clearly demonstrated that cholecystectomy not only significantly increases the risk of MASLD but also leads to characteristic changes in the body's blood metabolite profile and related biological pathways. Furthermore, this study identified 3-hydroxyacylcarnitine as a key molecule mediating the increased risk of MASLD associated with cholecystectomy. These findings provide important mechanistic evidence for elucidating the potential impact of cholecystectomy on human health.

[0046] The gallbladder, as the core organ for bile storage, concentration, and rhythmic release, plays a crucial role in fat digestion and absorption and maintaining metabolic homeostasis. Bile acids are the core components for bile to perform its physiological functions, effectively promoting fat emulsification and absorption. The enterohepatic circulation of bile acids and the physiological functions of the gallbladder work synergistically to maintain the body's metabolic balance. Cholecystectomy disrupts this finely regulated physiological system, causing bile to continuously flow into the intestines, losing its original rhythmic release characteristics, and triggering a series of chain reactions: adaptive upregulation of bile acid synthesis, enhanced transformation of bile acids by intestinal flora, and disruption of the enterohepatic circulation of bile acids, ultimately leading to elevated levels of bile acids in the intestines, with a significant increase in the proportion of secondary bile acids.

[0047] This study confirms that cholecystectomy can influence the risk of MASLD by interfering with fatty acid β-oxidation. The role of fatty acid β-oxidation dysfunction in the pathogenesis of MASLD is widely supported. As a key intermediate metabolite in medium-chain fatty acid β-oxidation, changes in the level of 3-hydroxycaprylyl carnitine directly reflect the efficiency and functional status of this metabolic pathway. Through Mendelian randomization analysis, this study further clarified the key mediating role of 3-hydroxycaprylyl carnitine in the increased risk of MASLD after cholecystectomy: cholecystectomy has a causal effect on elevated blood 3-hydroxycaprylyl carnitine levels, and elevated 3-hydroxycaprylyl carnitine significantly increases the risk of MASLD. Possible mechanisms include: on the one hand, the accumulation of such β-oxidation intermediates can promote the re-esterification of incompletely degraded fatty acids into triglycerides, leading to massive lipid deposition in hepatocytes and ultimately causing hepatic steatosis; on the other hand, elevated 3-hydroxycaprylyl carnitine may further exacerbate the risk of MASLD by inducing mitochondrial oxidative stress and activating inflammatory responses. These findings deepen our understanding of metabolic sequelae after cholecystectomy and provide a potential theoretical basis for future monitoring and intervention of MASLD in such patients.

Claims

1. Application of substances that detect 3-hydroxyoctanoylcarnitine in the preparation of products for the diagnosis of metabolic liver disease after cholecystectomy.

2. The application as described in claim 1, characterized in that, The substance is a reagent for detecting the content of 3-hydroxyoctanoylcarnitine.

3. A kit for the auxiliary diagnosis of metabolic liver disease after cholecystectomy, characterized in that, This includes reagents for detecting 3-hydroxyoctanoylcarnitine.

4. Application of active substances that reduce the level of 3-hydroxyoctanoylcarnitine in the body in the preparation of drugs for the prevention or treatment of metabolic liver disease after cholecystectomy.

5. The application as described in claim 4, characterized in that, The drug may be a small molecule inhibitor, adsorbent, metabolism promoter, or biological agent.

6. The application as described in claim 5, characterized in that, The small molecule inhibitor refers to a compound that specifically inhibits the key enzyme that catalyzes the formation of 3-hydroxyoctanoylcarnitine.

7. The application as described in claim 5, characterized in that, The adsorbent refers to a molecule that can specifically bind to and remove 3-hydroxyoctanoylcarnitine in the intestines or blood.

8. The application as described in claim 5, characterized in that, The metabolic promoters refer to compounds that activate the enzymatic pathway that further metabolizes 3-hydroxyoctanoylcarnitine.

9. The application as described in claim 5, characterized in that, The biological agent refers to a monoclonal antibody or fragment thereof that specifically targets and neutralizes 3-hydroxyoctanoylcarnitine.

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