Journal: bioRxiv

Article Title: The selective OX1R antagonist 1-SORA-51 reduces binge-like feeding behavior in male and female mice without detectable changes in dopamine

doi: 10.64898/2026.04.24.720455

Figure Lengend Snippet: All C57BL/6J mice were pre-exposed to the high-fat diet for 48 hours with std. chow, and then intermittently exposed the high-fat diet (along with std. chow) for 24 hours each binge session. 1A, B) Food intake was assessed over 24 hours for both male (n=10) and female (n=10) mice for the day prior (chow only) to a binge session and then a 24-hour binge session (chow with the high-fat diet). Males and females displayed binge-like feeding behavior with highly significant increases in total kcal/g BW consumed during binge sessions compared to the chow-only consumption. C) A 2-hour timepoint (to match food intake measurements after treatments) revealed significant binge-like behavior compared to a chow-only session for males and females. D-G) No effect of DORA-22 (100 mg/kg) was observed on binge-like feeding at the 2- or 24-hour timepoints for both sexes (n= 9 males, 10 females). All error bars are S.E.M.

Article Snippet: The high-fat diet used for all studies (5TJN, TestDiet, Richmond, Indiana) provides 4.55 kcal/g with the following caloric breakdown: protein 15.8%, fat 39.1%, and carbohydrates 45.1%.

Techniques:

Journal: bioRxiv

Article Title: The selective OX1R antagonist 1-SORA-51 reduces binge-like feeding behavior in male and female mice without detectable changes in dopamine

doi: 10.64898/2026.04.24.720455

Figure Lengend Snippet: All C57BL/6J mice were pre-exposed to the high-fat diet for 48 hours with std. chow, and then intermittently exposed the high-fat diet (along with std. chow) for 24 hours each binge session. A) A significant reduction in binge-like feeding was observed at the 2-hour timepoint for male mice treated with 1-SORA-51 (100 mg/kg) compared to vehicle treatment sessions (vehicle n=10, 1-SORA-51 n=8). B) The effect of 1-SORA-51 did not last across the 24-hour period. C) Similarly, a significant reduction in binge-like feeding was observed at the 2-hour timepoint for female mice treated with 1-SORA-51 (100 mg/kg) compared to vehicle treatment sessions (vehicle n=8, 1-SORA-51 n=9). D) The effect of 1-SORA-51 did not last across the 24-hour period. All error bars are S.E.M.

Article Snippet: The high-fat diet used for all studies (5TJN, TestDiet, Richmond, Indiana) provides 4.55 kcal/g with the following caloric breakdown: protein 15.8%, fat 39.1%, and carbohydrates 45.1%.

Techniques:

Journal: bioRxiv

Article Title: The selective OX1R antagonist 1-SORA-51 reduces binge-like feeding behavior in male and female mice without detectable changes in dopamine

doi: 10.64898/2026.04.24.720455

Figure Lengend Snippet: A) Male and female mice (n=9) expressing the GRABDA 2m sensor and finished binge training underwent fiber photometry sessions, during which baseline was recorded prior to treatment via gavage, and then provided access to the high-fat diet for 2 hours. Shown here is fluorescence normalized to baseline. No effect of treatment was seen during the 30 minutes after gavage or after HF pellet delivery. B) Treatment with 1-SORA-51 resulted in significantly less high-fat pellet consumption compared to vehicle sessions. All error bars are S.E.M.

Article Snippet: The high-fat diet used for all studies (5TJN, TestDiet, Richmond, Indiana) provides 4.55 kcal/g with the following caloric breakdown: protein 15.8%, fat 39.1%, and carbohydrates 45.1%.

Techniques: Expressing, Fluorescence

Journal: Cells

Article Title: Deletion of Perilipin 5 Protects against Hepatic Injury in Nonalcoholic Fatty Liver Disease via Missing Inflammasome Activation

doi: 10.3390/cells9061346

Figure Lengend Snippet: Absence of Perilipin 5 prevents high-fat diet (HFD)-induced liver injury. Serum and whole blood analysis from wild type (WT) and Plin5 −/− mice fed either a normal chow or HFD for 30 weeks ( n = 4–7 animals/group). Serum analysis showed that enzymes such as alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine transaminases (ALT) after HFD were only increased in WT. Lactate dehydrogenase (LDH), bilirubin, lipase, cholesterol, glucose, iron and white blood cells were differentially present among the different groups. Total protein and circulating triglycerides were present in all groups without statistical differences. Data are expressed as mean ± SD. Statistical analysis was performed with Student’s t -test. * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: WT ( n = 24) and Plin5 −/− ( n = 22) mice were fed ad libitum for 30 weeks on a mouse normal chow (NC) composed of 58% carbohydrates, 33% protein and 9% fat (V1534, ssniff Spezialdiäten GmbH, Soest, Germany), or a HFD containing 40% fat, 20% fructose and 2% cholesterol (D17010102, Research Diets, Inc., New Brunswick, NJ, USA).

Techniques:

Journal: Journal of Lipid Research

Article Title: Low production of 12α-hydroxylated bile acids prevents hepatic steatosis in Cyp2c70 −/− mice by reducing fat absorption

doi: 10.1016/j.jlr.2021.100134

Figure Lengend Snippet: Female, but not male, Cyp2c70 −/− mice are protected from WTD-induced obesity despite unaffected food intake. A: BW development as percent of initial weight (data are presented as mean ± SEM) and as grams gained in male and female Cyp2c70 −/− mice and WT littermates during 12 weeks of WTD feeding. B: Average daily food intake in male and female Cyp2c70 −/− mice and WT littermates during 12 weeks of WTD feeding. C: Fat mass and lean mass in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding as determined by MiniSpec. D: gWAT weights as percent of BW in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. E: Liver weights as percent of BW in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. N = 7–10 mice/group. Data are presented as Tukey's box-and-whisker plots unless specified, and P values represent ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001 by Kruskal-Wallis H testing followed by Conover posthoc comparisons. gWAT, gonadal white adipose tissue; OGTT, oral glucose tolerance test.

Article Snippet: Individually housed male and female Cyp2c70 −/− mice (male = 8 and female = 8) and WT littermates (male = 7 and female = 10) received a WTD with 60% (energy) fat and 0.25% cholesterol (D14010701Bi; Research Diets, Inc, New Brunswick, NJ) for 12 weeks, starting at the age of 12–14 weeks.

Techniques: Whisker Assay

Journal: Journal of Lipid Research

Article Title: Low production of 12α-hydroxylated bile acids prevents hepatic steatosis in Cyp2c70 −/− mice by reducing fat absorption

doi: 10.1016/j.jlr.2021.100134

Figure Lengend Snippet: Cyp2c70 deficiency induces a human-like hydrophobic bile acid pool in mice with a high abundance of chenodeoxycholic acid, particularly in females, and reduces hepatic bile acid synthesis. A: Bile acid composition and (B) ratio of 12α-/non-12α-hydroxylated BAs in gallbladder bile of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. C: Hydrophobicity index of biliary bile acids. D: Bile acid concentrations in plasma of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. E: Fecal bile acid excretion in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. F: Hepatic mRNA levels of genes involved in bile acid synthesis and transport in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. G: Ileal mRNA levels of genes involved in bile acid synthesis in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. N = 7–10 mice/group. Data are presented as Tukey's box-and-whisker plots, and P values represent ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001 by Kruskal-Wallis H testing followed by Conover posthoc comparisons. Bsep , bile salt export pump; Cyp7a1 , cholesterol 7α-hydroxylase; Cyp8b1 , sterol 12α-hydroxylase; Fgf15 , fibroblast growth factor 15; Fxr , farnesoid X receptor; Ibabp , ileal bile acid-binding protein; Ntcp , Na + -taurocholate cotransporting polypeptide; Shp , small heterodimeric partner.

Article Snippet: Individually housed male and female Cyp2c70 −/− mice (male = 8 and female = 8) and WT littermates (male = 7 and female = 10) received a WTD with 60% (energy) fat and 0.25% cholesterol (D14010701Bi; Research Diets, Inc, New Brunswick, NJ) for 12 weeks, starting at the age of 12–14 weeks.

Techniques: Clinical Proteomics, Whisker Assay, Binding Assay

Journal: Journal of Lipid Research

Article Title: Low production of 12α-hydroxylated bile acids prevents hepatic steatosis in Cyp2c70 −/− mice by reducing fat absorption

doi: 10.1016/j.jlr.2021.100134

Figure Lengend Snippet: Cyp2c70 −/− mice are protected from WTD-induced hepatic steatosis. A: Representative images of H&E-stained liver sections of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. Bar represents 300 μm. B: Hepatic triglyceride and cholesterol contents of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding, with average hepatic triglyceride and cholesterol contents in chow-fed female Cyp2c70 −/− mice indicated (dashed line) for comparison. C: Hepatic mRNA levels of LXRα , Srebp1c , and lipogenic genes ( Acc1 , Fasn , and Scd1 ) in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. D: Hepatic mRNA levels of genes involved in VLDL assembly ( Mttp and Tm6sf2 ), FA oxidation ( Pparα , Cpt1a , and Acox1 ) and cholesterol synthesis ( Srebp2 and Hmgcr ) in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. N = 7–10 mice/group. Data are presented as Tukey's box-and-whisker plots. P values represent ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001 by Kruskal-Wallis H testing followed by Conover posthoc comparisons. Acc1 , acetyl-CoA carboxylase; Acox1 , acyl-coenzyme A oxidase 1; Cpt1a , carnitine palmitoyltransferase 1A; Fasn , FA synthase; Hmgcr , 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; Lxrα , liver X receptor alpha; Mttp , microsomal triglyceride transfer protein; Pparα , peroxisome proliferator-activated receptor-alpha; Scd1 , acyl-CoA desaturase 1; Srebp1c , sterol regulatory element-binding transcription protein 1c; Srebp2 , sterol regulatory element-binding transcription protein 2; Tm6sf2 , transmembrane 6 superfamily member 2.

Article Snippet: Individually housed male and female Cyp2c70 −/− mice (male = 8 and female = 8) and WT littermates (male = 7 and female = 10) received a WTD with 60% (energy) fat and 0.25% cholesterol (D14010701Bi; Research Diets, Inc, New Brunswick, NJ) for 12 weeks, starting at the age of 12–14 weeks.

Techniques: Staining, Comparison, Whisker Assay, Binding Assay

Journal: Journal of Lipid Research

Article Title: Low production of 12α-hydroxylated bile acids prevents hepatic steatosis in Cyp2c70 −/− mice by reducing fat absorption

doi: 10.1016/j.jlr.2021.100134

Figure Lengend Snippet: Cholangiopathy and portal fibrosis in WTD-fed Cyp2c70 −/− mice, particularly in females. A: Liver damage markers aminotransferase and alanine aminotransferase in plasma of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. B: Representative images of Sirius Red–stained liver sections of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. Bar represents 300 μm. C: Hepatic mRNA levels of genes involved in fibrogenesis, inflammation, and senescence in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. D: Representative images of liver sections stained for the cholangiocyte marker CK19 in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. Bar represents 300 μm. E: Plasma albumin concentrations in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. N = 7–10 mice/group. Data are presented as Tukey's box-and-whisker plots. P values represent ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001 by Kruskal-Wallis H testing followed by Conover posthoc comparisons. ALT, alanine aminotransferase; AST, aspartate aminotransferase; Col1a1 , collagen type I alpha 1 chain; Col1a2 , collagen type I alpha 2 chain; CK19, cytokeratin 19; Krt19 , keratin 19; Mcp1 , monocyte-chemoattractant protein 1; Emr1 , F4/80 , EGF-like module-containing mucin-like hormone receptor-like 1; Cdkn2a , P16-INK4A , cyclin-dependent kinase inhibitor 2A.

Article Snippet: Individually housed male and female Cyp2c70 −/− mice (male = 8 and female = 8) and WT littermates (male = 7 and female = 10) received a WTD with 60% (energy) fat and 0.25% cholesterol (D14010701Bi; Research Diets, Inc, New Brunswick, NJ) for 12 weeks, starting at the age of 12–14 weeks.

Techniques: Clinical Proteomics, Staining, Marker, Whisker Assay

Journal: Journal of Lipid Research

Article Title: Low production of 12α-hydroxylated bile acids prevents hepatic steatosis in Cyp2c70 −/− mice by reducing fat absorption

doi: 10.1016/j.jlr.2021.100134

Figure Lengend Snippet: No indications for stimulation of BAT or browning of white adipose depots in WTD-fed Cyp2c70 −/− mice. A: BAT weights as percent of BW in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. B: Representative images of H&E-stained BAT from male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. Bar represents 300 μm. C: BAT mRNA levels of bile acids receptors Fxr and Tgr5 and thermogenic genes Ucp1 and Dio2 in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. D: Representative images of H&E-stained subcutaneous white adipose tissue from male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. Bar represents 100 μm. E: mRNA levels of the thermogenic gene Ucp1 in subcutaneous white adipose tissue in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. N = 7–10 mice/group. Data are presented as Tukey's box-and-whisker plots. P values represent ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001 by Kruskal-Wallis H testing followed by Conover posthoc comparisons. Dio2 , iodothyronine deiodinase 2; Fxr , farnesoid X receptor; Tgr5 , takeda G protein-coupled receptor 5; Ucp1 , mitochondrial uncoupling protein 1.

Article Snippet: Individually housed male and female Cyp2c70 −/− mice (male = 8 and female = 8) and WT littermates (male = 7 and female = 10) received a WTD with 60% (energy) fat and 0.25% cholesterol (D14010701Bi; Research Diets, Inc, New Brunswick, NJ) for 12 weeks, starting at the age of 12–14 weeks.

Techniques: Staining, Whisker Assay

Journal: Journal of Lipid Research

Article Title: Low production of 12α-hydroxylated bile acids prevents hepatic steatosis in Cyp2c70 −/− mice by reducing fat absorption

doi: 10.1016/j.jlr.2021.100134

Figure Lengend Snippet: Cholesterol and FA absorption are reduced in WTD-fed Cyp2c70 −/− mice, particularly in females. A: Fecal neutral sterol excretion in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. B: mRNA levels of the cholesterol transporter Npc1l1 in jejunum of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. C: Plasma concentrations of biomarkers of cholesterol absorption (campesterol, sitosterol, and cholestanol) normalized to cholesterol in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. D: Fecal energy content in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding determined by bomb calorimetry. E: Total fecal FA excretion (left panel) and fat absorption efficiency (right panel) in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. Fecal FA composition can be found in supplemental Table S5 . F: Representative fluorescence microscope images of jejunum collected 2 h after gavage with BODIPY-labeled palmitic acid in olive oil in male and female Cyp2c70 −/− mice and WT littermates after 8 weeks of WTD feeding. Bar represents 50 μm. G: Representative transmission electron micrographs of jejunum collected from 8-week WTD-fed female Cyp2c70 −/− mice and WT littermates at 2 h after BODIPY-labeled oil gavage. Bar represents 5 μm for upper panels and 1 μm for lower panels. N = 6–10 mice/group. Data are presented as Tukey's box-and-whisker plots. P values represent ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001 by Kruskal-Wallis H testing followed by Conover posthoc comparisons. Npc1l1 , Niemann-Pick C1-like intracellular cholesterol transporter 1.

Article Snippet: Individually housed male and female Cyp2c70 −/− mice (male = 8 and female = 8) and WT littermates (male = 7 and female = 10) received a WTD with 60% (energy) fat and 0.25% cholesterol (D14010701Bi; Research Diets, Inc, New Brunswick, NJ) for 12 weeks, starting at the age of 12–14 weeks.

Techniques: Clinical Proteomics, Fluorescence, Microscopy, Labeling, Transmission Assay, Whisker Assay

Journal: Journal of Lipid Research

Article Title: Low production of 12α-hydroxylated bile acids prevents hepatic steatosis in Cyp2c70 −/− mice by reducing fat absorption

doi: 10.1016/j.jlr.2021.100134

Figure Lengend Snippet: Altered bile acid composition rather than perturbed bile formation explains impaired fat absorption in WTD-fed Cyp2c70 −/− mice. A: Bile flow and biliary secretion rates of bile acids, phospholipids, and cholesterol in male and female Cyp2c70 −/− mice and WT littermates after 8 weeks of WTD feeding. B: Hepatic mRNA levels of genes involved in biliary phospholipid and cholesterol secretion in male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. C: Molar ratios of phospholipids and cholesterol, respectively, to bile acids in bile of male and female Cyp2c70 −/− mice and WT littermates after 8 weeks of WTD feeding. D: mRNA levels of genes involved in enterocytic phosphatidylcholine synthesis, in jejunum of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. E: mRNA expression of Cd36 , an FA transporter, in jejunum of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. F: mRNA levels of Fatp4 , involved in enterocytic triglyceride transport in jejunum of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. G: Relationships between biliary 12α/non-12α-hydroxylated bile acids and FA absorption (left panel), fecal FA excretion (middle panel), and hepatic triglyceride content (right panel) across all groups of male and female Cyp2c70 −/− mice and WT littermates after 12 weeks of WTD feeding. H: The associations between the relative abundances of Erysipelotrichaceae (%) and biliary 12α/non-12α hydroxylated BAs (left panel), FA absorption (middle panel), and hepatic total cholesterol levels (right panel). N = 7–10 mice/group. Significance of differences between groups was accessed using Kruskal-Wallis H testing followed by Conover posthoc comparisons (panels A–F), whereas linear correlation analysis was performed in panels G–H. ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001, and ∗∗∗∗ P < 0.0001. Abcb4 , ATP-binding cassette subfamily B member 4; Abcg5 , ATP-binding cassette subfamily G member 5; Abcg8 , ATP-binding cassette subfamily G member 8; Cd36 , cluster of differentiation 36; Ctpct , cytidine 5′-triphosphate: phosphocholine cytidylyltransferase; Fatp4 , FA transport protein 4; Lpcat3 , lysophosphatidylcholine acyltransferase 3.

Article Snippet: Individually housed male and female Cyp2c70 −/− mice (male = 8 and female = 8) and WT littermates (male = 7 and female = 10) received a WTD with 60% (energy) fat and 0.25% cholesterol (D14010701Bi; Research Diets, Inc, New Brunswick, NJ) for 12 weeks, starting at the age of 12–14 weeks.

Techniques: Expressing, Binding Assay