LDT409 (pan-PPAR partial agonist) mitigates metabolic dysfunction-associated steatotic liver disease in high-fructose-fed mice.
Study Goal
The researchers aimed to evaluate the effects of a high-fructose diet on hepatic remodeling, energy metabolism, and endoplasmic reticulum stress in mice, and assess the potential benefits of LDT409 in mitigating these effects.
Results Summary
The high-fructose diet induced insulin resistance and ER stress, increased liver steatosis, and upregulated pro-fibrogenic genes. LDT409 treatment reduced lipogenic factors, mitigated ER stress, and enhanced beta-oxidation, suggesting potential benefits for metabolic dysfunction-associated steatotic liver disease.
Population
Male C57BL/6 mice
Effective Dosage
40 mg/kg of body weight (mixed with diet)
Duration
5 weeks (treatment phase after 10 weeks of dietary intervention)
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
high-fructose diet | increase | insulin resistance | Male C57BL/6 mice | - | caused | #1 |
high-fructose diet | increase | endoplasmic reticulum (ER) stress | Male C57BL/6 mice | - | caused | #2 |
high-fructose diet | increase | Pparg expression | Male C57BL/6 mice | - | increased | #3 |
high-fructose diet | decrease | Ppara expression | Male C57BL/6 mice | - | decreased | #4 |
high-fructose diet | increase | steatosis | Male C57BL/6 mice | - | increased | #5 |
high-fructose diet | increase | pro-fibrogenic gene expression | Male C57BL/6 mice | - | increased | #6 |
LDT409 | decrease | lipogenic factors | Male C57BL/6 mice | - | suppressed | #7 |
LDT409 | decrease | ER stress | Male C57BL/6 mice | - | mitigated | #8 |
LDT409 | increase | beta-oxidation | Male C57BL/6 mice | - | increase in | #9 |
AIM: This study sought to evaluate the effects of LDT409, a pan-PPAR partial agonist obtained from the main industrial waste from cashew nut processing, on hepatic remodeling, highlighting energy metabolism and endoplasmic reticulum (ER) stress in high-fructose-fed mice. METHODS: Male C57BL/6 mice received a control diet (C) or a high-fructose diet (HFRU) for ten weeks. Then, a five-week treatment started: C, C-LDT409, HFRU, and HFRU-LDT409. The LDT409 (40 mg/kg of body weight) was mixed with the diets. RESULTS: The HFRU diet caused insulin resistance and endoplasmic reticulum (ER) stress. High Pparg and decreased Ppara expression increased steatosis and pro-fibrogenic gene expression in livers of HFRU-fed mice. Suppressed lipogenic factors, orchestrated by PPAR-gamma, and mitigated ER stress concomitant with the increase in beta-oxidation driven by PPAR-alpha mediated the LDT409 beneficial effects. CONCLUSIONS: LDT409 may represent a potential low-cost approach to treat metabolic dysfunction-associated steatotic liver disease, which does not currently have a specific treatment.