Dietary HDCA (0.625% for 8 weeks after 4 weeks of HFHS feeding) reduced hepatic triglycerides and disease scores in wild-type mice; the response was absent in global Pparα-knockout mice. This supports a PPARα requirement in this model. [1]
In female LDLR-knockout mice, 1.25% dietary HDCA for 15 weeks reduced atherosclerotic lesion size relative to chow alone. Lesions still progressed from the Western-diet baseline, and plasma triglycerides increased by 28% versus chow. [2]
Oral HDCA (50 mg/kg, three times weekly for 6 weeks) improved glucose tolerance and reduced weight gain in western-style-diet-fed wild-type mice; these benefits were absent in TGR5-knockout mice. Fasting glucose was unchanged in wild-type mice despite increased fasting insulin. [3]
PPARα-dependent hepatic response to dietary HDCA
Animal study · Male C57BL/6N wild-type and global Pparα-knockout mice; 8 weeks old at entry; HFHS diet [1]
The reduction in liver triglycerides, steatosis, inflammation and NAFLD activity score seen in wild-type mice was absent in global Pparα-knockout mice. Energy intake was not significantly changed. This genotype experiment supports a PPARα requirement under the reported conditions.
Conditions shared by the study groups
- Route
- Oral, in diet
- Frequency
- Dietary supplementation
- Treatment course
- 8 weeks, beginning after 4 weeks HFHS
- Wild-type HDCA
- Model: Male C57BL/6N wild-type
- Pparα-knockout HDCA
- Model: Male C57BL/6N Pparα−/−
Methods and source locations
Compound reported in the paper: Hyodeoxycholic acid; Compound label in the paper: HDCA
Compound-level research evidence; supplier-specific material and Adooq lot performance are not established.
Figure 5a–h; Methods Animal studies and Animal experiment 4
Liver triglycerides, histological scores and inflammatory cytokines: Liver TG assay, histological scoring, cytokine assays and immunoblot; mean ± SEM; two-tailed Student’s t test as caption reports. — Figure 5c–h and caption; Results The anti-NAFLD effect of HDCA is hepatic PPARα-dependent
Wild-type HDCA · Figure 5a–h; Methods Animal studies and Animal experiment 4
Pparα-knockout HDCA · Figure 5a–h; Methods Animal studies and Animal experiment 4
Slower atherosclerotic lesion progression in female LDLR-knockout mice
Animal study · Female LDLR-knockout mice; Western diet for 8 weeks from age 8 weeks, followed by chow with or without HDCA for 15 weeks [2]
HDCA reduced lesion size relative to chow alone at three sites, but lesions still grew from the Western-diet baseline. Plasma triglycerides increased rather than decreased in this long-term experiment.
Conditions shared by the study groups
- Route
- Oral, in diet
- Frequency
- Dietary supplementation
- Treatment course
- 15 weeks after 8 weeks Western diet
- HDCA diet after Western diet
- Model: Female LDLR-knockout mice
Methods and source locations
Compound reported in the paper: Hyodeoxycholic acid; Compound label in the paper: HDCA
Compound-level research evidence; supplier-specific material and Adooq lot performance are not established.
Figure 1a–e; Table 4; Methods Animals and study design; Results HDCA inhibited atherosclerotic lesion formation
Atherosclerotic lesion size versus chow: Histomorphometry and en face analysis; Figure 1 lines/error bars mean ± SE; percentages explicitly stated in Results, not estimated from plot. — Figure 1a–c and corresponding Results paragraph
Aortic-root lesion regression from baseline: Comparison with separate baseline group euthanized after 8-week Western diet. — Figure 1a; Results lesion progression paragraph
Plasma triglycerides versus chow after 15-week intervention: Enzymatic colorimetric assay. Table 4 reports means ± SD; chow n = 12, HDCA n = 14. Not conflated with short-term cohort. — Table 4 and corresponding Results; Discussion triglyceride inconsistency paragraph
Lesion smooth-muscle-cell content: α-actin immunohistochemistry; 4–6 mice/group and 3–5 lesion sections/mouse as caption specifies. — Figure 1e; corresponding Results paragraph
HDCA diet after Western diet · Figure 1a–e; Table 4; Methods Animals and study design; Results HDCA inhibited atherosclerotic lesion formation
TGR5-dependent response to oral HDCA
Animal study · Male wild-type and TGR5-knockout mice fed western-style diet [3]
HDCA reduced body-weight gain and improved oral glucose tolerance in wild-type mice, with no corresponding benefit in TGR5-knockout mice. Wild-type fasting insulin increased while fasting glucose was unchanged.
Conditions shared by the study groups
- Route
- Intragastric gavage
- Frequency
- Three times weekly
- Treatment course
- 6 weeks
- Vehicle
- Olive oil
- Wild-type oral HDCA
- Model: Male WT mice on western-style diet
- TGR5-knockout oral HDCA
- Model: Male TGR5 KO mice on western-style diet
Methods and source locations
Compound reported in the paper: Hyodeoxycholic acid; Compound label in the paper: HDCA
Compound-level research evidence; supplier-specific material and Adooq lot performance are not established.
Figure 5a–c,e–h (vehicle and HDCA groups only); Results HDCA activates TGR5 in vitro and in vivo; Methods Diets and pharmacological treatments and OGTT
Body-weight gain and oral glucose tolerance: OGTT and body-weight monitoring; n = 6–10 per WT condition and n = 5 per TGR5 KO condition; mean ± SEM. Caption reports two-way ANOVA with Bonferroni for body weight and Mann–Whitney for two-group comparisons. — Figure 5a,c,e,g; Results HDCA activates TGR5 in vitro and in vivo
Fasting glucose and insulin: Fasting measurements and insulin ELISA; mean ± SEM. — Figure 5b,f and corresponding Results paragraph
Wild-type oral HDCA · Figure 5a–c,e–h (vehicle and HDCA groups only); Results HDCA activates TGR5 in vitro and in vivo; Methods Diets and pharmacological treatments and OGTT
TGR5-knockout oral HDCA · Figure 5a–c,e–h (vehicle and HDCA groups only); Results HDCA activates TGR5 in vitro and in vivo; Methods Diets and pharmacological treatments and OGTT
