Journal: bioRxiv

Article Title: Macronutrient Composition and Genetic Background Determine the Response to a Ketogenic Diet

doi: 10.64898/2026.04.23.720368

Figure Lengend Snippet: a. Heatmap of secreted protein expression in liver on KD-5%P, KD-10%P and chow. b. Circulating GDF15 levels of WT B6J mice fed with KD-5%P, KD-10%P and chow. c. Circulating FGF21 levels of WT B6J mice fed with KD-5%P, KD-10%P and chow. d. The schematic of ablating GFRAL-neurons in Area Postrema and the resulting body weight, cumulative calories consumed (kcal), and body composition of WT B6J mice under KD-5%P or KD-10%P. e. Body weight and cumulative calories consumed of B6NJ-GDF15 whole-body knockout and control mice under KD-5%P or KD-10%P. (n = 3 mice for DTA fed with KD-10%P and mCherry with KD-10%P; n=7 for DTA fed with KD-5%P and n=9 for mCherry fed with KD-5%P. GDF15-KO experiment has n=2 in each group. Data are presented as mean ± s.e.m. NS, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.)

Article Snippet: Wild-type C57BL/6J (#000664), C57BL/6NJ (#005304), FVB/NJ(#001800), DBA/2J (# 000671), Fgf21-KO (B6.129Sv(Cg)-Fgf21 tm1.1Djm /J, #033846), Gfral-cre(B6;SJL-Gfral em1(cre)Rsy /J, #036750), Gdf15 nuGFP-CE (C57BL/6 Gdf15tm1(cre/ERT2)Amc/J, 034497) were obtained from Jackson Lab. OB F1 were obtained from Jackson Lab, then bred in lab, from crossing male OB and female ob/+(#000632).

Techniques: Expressing, Knock-Out, Control

Journal: bioRxiv

Article Title: Macronutrient Composition and Genetic Background Determine the Response to a Ketogenic Diet

doi: 10.64898/2026.04.23.720368

Figure Lengend Snippet: a. Glucose tolerance test (2mg glucose/kg body weight) and calculated area under the curve of mice ablating GFRAL-neurons in Area Postrema and control mice under KD-5%P or KD-10%P. b. Serum glucose levels of B6NJ-Gdf15 whole-body knockout mice under KD-5%P or KD-10%P. c. Glucose tolerance test (2mg glucose/kg body weight) and calculated area under the curve of WT B6J or B6NJ mice under KD-5%P or KD-10%P. d. Serum glucose levels of WT B6J or B6NJ mice under KD-5%P or KD-10%P. e. Serum ketone levels of WT B6J or B6NJ mice under KD-5%P or KD-10%P. f. Hepatic glycogen levels of WT B6J or B6NJ mice under KD-5%P or KD-10%P. g. Hepatic saponified fatty acids profiles of WT B6J or B6NJ mice under KD-5%P or KD-10%P. h. Body weight, cumulative calorie intake (Kcal), and body composition of female WT B6NJ mice under KD-5%P or KD-10%P. i. Circulating GDF15 levels of female WT B6NJ mice under KD-5%P or KD-10%P. j. Serum glucose levels of female WT B6NJ mice under KD-5%P or KD-10%P. k. Serum ketone levels of female WT B6NJ mice under KD-5%P or KD-10%P. l. Glucose tolerance test (2mg glucose/kg body weight) and calculated area under the curve of female WT B6NJ mice under KD-5%P or KD-10%P. (n = 5 for all groups. All glucose/ketone are done by testing 2 individual days of the same group of mice. Data are presented as mean ± s.e.m. NS, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.)

Article Snippet: Wild-type C57BL/6J (#000664), C57BL/6NJ (#005304), FVB/NJ(#001800), DBA/2J (# 000671), Fgf21-KO (B6.129Sv(Cg)-Fgf21 tm1.1Djm /J, #033846), Gfral-cre(B6;SJL-Gfral em1(cre)Rsy /J, #036750), Gdf15 nuGFP-CE (C57BL/6 Gdf15tm1(cre/ERT2)Amc/J, 034497) were obtained from Jackson Lab. OB F1 were obtained from Jackson Lab, then bred in lab, from crossing male OB and female ob/+(#000632).

Techniques: Control, Knock-Out

Journal: bioRxiv

Article Title: Macronutrient Composition and Genetic Background Determine the Response to a Ketogenic Diet

doi: 10.64898/2026.04.23.720368

Figure Lengend Snippet: a. Body weight, cumulative calories consumed, and body composition of WT B6J and B6NJ mice under KD-5%P or KD-10%P. b. Serum GDF15 levels of WT B6J and B6NJ mice under KD-5%P or KD-10%P. c. The schematic of hepatic AAV-induced Nnt expression in B6J mice and the resulting body weight, cumulative calories consumed, and body composition of both groups under KD-5%P. d. Serum GDF15 levels of AAV-induced Nnt expression and control mice under KD-5%P. e, f. As in c, d, for B6NJ Nnt whole-body knockout mice. (n = 5 for each B6J and B6NJ group, n=5 for AAV-induced Nnt expression and control group. n=8 for Nnt-WT, n=7 for Nnt-KO. Data are presented as mean ± s.e.m. NS, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.)

Article Snippet: Wild-type C57BL/6J (#000664), C57BL/6NJ (#005304), FVB/NJ(#001800), DBA/2J (# 000671), Fgf21-KO (B6.129Sv(Cg)-Fgf21 tm1.1Djm /J, #033846), Gfral-cre(B6;SJL-Gfral em1(cre)Rsy /J, #036750), Gdf15 nuGFP-CE (C57BL/6 Gdf15tm1(cre/ERT2)Amc/J, 034497) were obtained from Jackson Lab. OB F1 were obtained from Jackson Lab, then bred in lab, from crossing male OB and female ob/+(#000632).

Techniques: Expressing, Control, Knock-Out

Journal: bioRxiv

Article Title: Macronutrient Composition and Genetic Background Determine the Response to a Ketogenic Diet

doi: 10.64898/2026.04.23.720368

Figure Lengend Snippet: a. Glucose tolerance test (2mg glucose/kg body weight) and calculated area under the curve of Gfral-ablation and control mice under KD-5%P or KD-10%P. b. Glucose tolerance test (2mg glucose/kg body weight) and calculated area under the curve of B6NJ-Nnt whole-body knockout mice under KD-5%P or KD-10%P. c. Glucose tolerance test (2mg glucose/kg body weight) and calculated area under the curve of B6J mice with NNT re-expression under KD-5%P or KD-10%P. d. Body weight, cumulative calorie intake (Kcal) and body composition of DBA/2J mice on KD-5%P or KD-10%P. e. Glucose tolerance test (2mg glucose/kg body weight) and calculated area under the curve of composition of DBA/2J mice under KD-5%P or KD-10%P. f. GDF15 levels of DBA/2J mice under KD-5%P or KD-10%P. g-i. As in d-f, for FVB/NJ mice. j. Western blot of Nnt in the liver of control or overexpression mice. (n = 5 for each group in DBA/2J, n=4 for each group in FVB/2J. All glucose/ketone are done by testing 2 individual days of the same group of mice. Data are presented as mean ± s.e.m. NS, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.)

Article Snippet: Wild-type C57BL/6J (#000664), C57BL/6NJ (#005304), FVB/NJ(#001800), DBA/2J (# 000671), Fgf21-KO (B6.129Sv(Cg)-Fgf21 tm1.1Djm /J, #033846), Gfral-cre(B6;SJL-Gfral em1(cre)Rsy /J, #036750), Gdf15 nuGFP-CE (C57BL/6 Gdf15tm1(cre/ERT2)Amc/J, 034497) were obtained from Jackson Lab. OB F1 were obtained from Jackson Lab, then bred in lab, from crossing male OB and female ob/+(#000632).

Techniques: Control, Knock-Out, Expressing, Western Blot, Over Expression

Journal: bioRxiv

Article Title: Macronutrient Composition and Genetic Background Determine the Response to a Ketogenic Diet

doi: 10.64898/2026.04.23.720368

Figure Lengend Snippet: a. Volcano plot of hepatic mRNA expression of B6J and B6NJ mice fed with KD-5%P versus KD-10%P at ad lib fasted state. b. Immune response pathway analysis between KD-5%P versus KD-10%P in B6J and B6NJ mice. c. Serum LCN2 levels of WT B6J and B6NJ mice under KD-5%P or KD-10%P. d. Body weight, cumulative calories consumed, and body composition of B6NJ-Nlrp12 whole-body knockout and littermate mice under KD-5%P or KD-10%P. e. Body weight, cumulative calories consumed (kcal) and body composition of B6J-Lcn2 whole-body knockout and littermate mice under KD-5%P or KD-10%P. f. Serum LCN2 levels of B6NJ-Nlrp12 whole-body knockout mice under KD-5%P or KD-10%P. g. Serum GDF15 levels of B6NJ-Nlrp12 whole-body knockout mice under KD-5%P or KD-10%P. (For a, b and d, n = 5 for each B6J and B6NJ group; n=10 for Nlrp12-KO under KD-5%P, n=8 for Nlrp12-KO under KD-10%P, and n=5 for both WT litter mate under 2 diets. For B6J-Lcn2 KO experiment, n=7 for KO under KD-5%P, n=5 for KO under KD-10%P and n=4 for WT under both diets. For serum Lcn2 and GDF15 measurement in B6NJ-Nlrp12-KO mice, n=5 for KD-10%P group and n=7 for KD-5%P group. Data are presented as mean ± s.e.m. NS, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.)

Article Snippet: Wild-type C57BL/6J (#000664), C57BL/6NJ (#005304), FVB/NJ(#001800), DBA/2J (# 000671), Fgf21-KO (B6.129Sv(Cg)-Fgf21 tm1.1Djm /J, #033846), Gfral-cre(B6;SJL-Gfral em1(cre)Rsy /J, #036750), Gdf15 nuGFP-CE (C57BL/6 Gdf15tm1(cre/ERT2)Amc/J, 034497) were obtained from Jackson Lab. OB F1 were obtained from Jackson Lab, then bred in lab, from crossing male OB and female ob/+(#000632).

Techniques: Expressing, Knock-Out

Journal: bioRxiv

Article Title: Macronutrient Composition and Genetic Background Determine the Response to a Ketogenic Diet

doi: 10.64898/2026.04.23.720368

Figure Lengend Snippet: a. Heatmap of mitochondrial stress gene markers of B6J mice fed with KD-5%P, KD-10%P and chow. b. Heatmap of oxidative stress gene markers of B6J mice fed with KD-5%P, KD-10%P and chow. c. The schematic of Isrib i.p. injection in B6J mice and the result body weight, cumulative food intake (Kcal) and body composition of both groups under KD-5%P or KD-10%P. d. Serum GDF15 levels of B6J mice treated with Isrib or Vehicle under KD-5%P or KD-10%P. e. Serum LCN2 levels of B6J mice treated with Isrib or Vehicle under KD-5%P or KD-10%P. f-h. As in c-e, for NAC treatment, control group is the same data. i. The schematic of the mechanism on how KD induces body weight loss (n = 5 mice for each group. Data are presented as mean ± s.e.m. NS, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.)

Article Snippet: Wild-type C57BL/6J (#000664), C57BL/6NJ (#005304), FVB/NJ(#001800), DBA/2J (# 000671), Fgf21-KO (B6.129Sv(Cg)-Fgf21 tm1.1Djm /J, #033846), Gfral-cre(B6;SJL-Gfral em1(cre)Rsy /J, #036750), Gdf15 nuGFP-CE (C57BL/6 Gdf15tm1(cre/ERT2)Amc/J, 034497) were obtained from Jackson Lab. OB F1 were obtained from Jackson Lab, then bred in lab, from crossing male OB and female ob/+(#000632).

Techniques: Injection, Control

Journal: bioRxiv

Article Title: Chronopharmacological targeting of mitochondrial dihydroorotate dehydrogenase prevents diet-induced obesity in male mice

doi: 10.64898/2026.04.18.719366

Figure Lengend Snippet: a, Daily food intake (g per mouse) measured in HFD-fed mice receiving daily intraperitoneal injections of vehicle (VEH) or BAY2402234 (BAY) at ZT0 or ZT12 for 7 consecutive days (n=20/group). b, Distribution of food intake between light and dark phases for the same conditions as in ( a) (n=4 cages/group). c, Representative immunoblots of hepatic FGF21 collected 4 h and 16 h after VEH or BAY injection at ZT0 (top) or ZT12 (bottom). LC, loading control. n=4/group/timepoint. d, Densitometric quantification of FGF21 normalized to LC at 4 h and 16 h after injection; ns, not significant; P < 0.05. e,g, Serum GDF15 measured 4 h and 16 h after VEH or BAY injection at ZT0 ( e ; sampling at ZT4 and ZT16) or ZT12 ( g ; sampling at ZT16 and ZT4), respectively. n=4/group/timepoint. f,h, Daily water intake following injections at ZT0 ( f ) or ZT12 ( h ). n=8/group/timepoint. Data are mean ± s.e.m. Statistical comparisons were performed between VEH and BAY at each matched time point; ns, not significant; * P < 0.05. All experiments were performed in male C57BL/6J mice.

Article Snippet: Serum GDF15 was measured with Mouse/Rat GDF15 Quantikine ELISA Kit (R&D Systems), following the manufacturer recommendations.

Techniques: Western Blot, Injection, Control, Sampling