CN-121995045-A - Application of 3-hydroxy octanoyl carnitine as target point of metabolic liver disease after cholecystectomy

Abstract

The invention provides an application of 3-hydroxy octanoyl carnitine as a target point of metabolic liver disease after cholecystectomy. According to the invention, through two-sample Mendelian randomization and intermediate analysis, the 3-hydroxyoctanoyl carnitine is proved to be a key causal mediating factor for MASLD risk increase caused by cholecystectomy for the first time, and the mediating ratio is 10.37%. This directly demonstrates that intervention at this metabolite level can affect disease progression.

Inventors

• JIN CHUANDI
• LI PEIPEI
• XU LIN
• GAO LINHUI

Assignees

• 山东省立第三医院

Dates

Publication Date

20260508

Application Date

20260211

Claims (9)

1. 1. The substance for detecting 3-hydroxy octanoyl carnitine is applied to the preparation of products for diagnosing metabolic liver diseases after cholecystectomy.
2. 2. The use according to claim 1, wherein the substance is a reagent for detecting the content of 3-hydroxyoctanoyl carnitine.
3. 3. A kit for auxiliary diagnosis of metabolic liver diseases after cholecystectomy is characterized by comprising a reagent for detecting 3-hydroxyoctanoyl carnitine.
4. 4. The use of an active substance that reduces the level of 3-hydroxyoctanoyl carnitine in vivo for the preparation of a medicament for the prevention or treatment of metabolic liver disease following cholecystectomy.
5. 5. The use according to claim 4, wherein the medicament is a small molecule inhibitor, an adsorbent, a metabolic promoter, a biological agent.
6. 6. The use according to claim 5, wherein the small molecule inhibitor is a compound that specifically inhibits a key enzyme that catalyzes the production of 3-hydroxyoctanoyl carnitine.
7. 7. The use according to claim 5, wherein the adsorbent is a molecule capable of specifically binding and scavenging 3-hydroxyoctanoyl carnitine in the intestinal tract or blood.
8. 8. The use according to claim 5, wherein the metabolic promoter is a compound that activates an enzyme pathway capable of further metabolizing 3-hydroxyoctanoyl carnitine.
9. 9. The use according to claim 5, wherein the biological agent is a monoclonal antibody or fragment thereof that specifically targets and neutralizes 3-hydroxyoctanoyl carnitine.

Description

Application of 3-hydroxy octanoyl carnitine as target point of metabolic liver disease after cholecystectomy Technical Field The invention belongs to the technical field of biological diagnosis and medicines, and particularly relates to application of 3-hydroxy octanoyl carnitine as a target for metabolic liver diseases after cholecystectomy. Background Cholecystectomy, i.e., removal of the gallbladder by surgery, remains a standardized treatment for gallbladder disease. As one of the most commonly performed surgical procedures worldwide, it has previously been considered safe 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 nonalcoholic fatty liver disease or NAFLD). MASLD is a chronic progressive liver disease and is mainly characterized by excessive accumulation of liver lipids without high volume drinking, usually associated with metabolic syndromes such as obesity, type II diabetes, hypertension and dyslipidemia. MASLD affects approximately one third of the world population, constituting a huge public health burden. This disease may progress to metabolic dysfunction-related fatty liver disease (MASH), which may lead to fibrosis, cirrhosis, and ultimately liver cancer, further exacerbating its global impact. Two cross-sectional studies reported an increased risk of MASLD following cholecystectomy. A large-scale longitudinal cohort study involving 18,656 korean adults showed that cholecystectomy was associated with a 1.48-fold increase in MASLD risk. In agreement with this, a systematic review and meta-analysis of 20 observational studies, involving 2730 ten thousand participants, revealed an increase in overall risk of liver disease after cholecystectomy of 63%, with a particularly elevated risk of non-alcoholic fatty liver disease (54%), cirrhosis (173%) and primary (46%). Cholecystectomy has clear association with an elevated risk of post-operative long term MASLD, but its specific pathogenesis is unclear, resulting in a clinical lack of targeted preventive and therapeutic measures. The existing MASLD management schemes (such as lifestyle intervention, insulin sensitizers) are not aimed at metabolic pathway disorders caused by the specific cause of cholecystectomy, and have limited curative effects and side effects. Currently, clinical interventions aimed at MASLD are mainly based on their broad metabolic abnormality profile, rather than on specific etiologies, mainly in the following therapeutic modes: 1. First line treatment, lifestyle intervention (weight loss, diet adjustment). The method is universal but depends on long-term compliance of patients, and has weak pertinence to specific metabolic disorders after operation. 2. Pharmaceutical treatments such as pioglitazone (improving insulin resistance), vitamin E (anti-oxidant), obeticholic acid (regulating bile acid metabolism). These drugs act on the downstream or bypass pathways of MASLD's onset, are not directed to the unique pathophysiological processes resulting from cholecystectomy, and have side effects such as weight gain, skin itching, etc. 3. Operation related management the current clinical guidelines only focus on perioperative safety and short-term complications of cholecystectomy, and there is no standard monitoring and prevention scheme for long-term metabolic sequelae (such as MASLD) caused by cholecystectomy, and no specific targeting drug. The above treatment method has the following disadvantages 1. The etiology is unknown, the existing method is not aimed at the new discovery of causal chain of cholecystectomy, specific metabolite disorder and liver injury, belongs to symptomatic treatment, and fails to radically block the occurrence of diseases. 2. Lack of early preventive targets means that no intervening biochemical mediators can be identified early after surgery, leading directly to MASLD, thereby missing a preventive opportunity. 3. The medicine is nonspecific, the existing medicine can be effective for the part MASLD after operation, but the curative effect/risk is lower because of the non-targeting property. Thus, there is a critical need in the clinic to elucidate the specific pathogenic mechanisms of post-operative MASLD and to develop targeted intervention strategies accordingly. Disclosure of Invention In order to solve the problems, the invention provides application of 3-hydroxy octanoyl carnitine as a target point of metabolic liver diseases after cholecystectomy. The invention provides a treatment idea of reducing the level of 3-hydroxy octanoyl carnitine. Under this core, there are a number of alternative implementations of specific interventions: 1. the alternative target point is that the 3-hydroxy octanoyl carnitine molecule can be directly targeted, and the upstream regulatory factor can be targeted. For example, the