Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Genetic ablation of JNK1 in SF1 neurons. (A) Demonstration of Cre recombinase activity, as shown by the presence of red fluorescent td-Tomato in the VMH of t d-Tomato Sf1 Cre /Jnk1 fl/fl reporter mice but not control animals (20X; Scale bar: 100 μm). (B) Representative confocal images (40X; Scale bar: 100 μm). (C) % of JNK1 positive cells in the VMH ( n = 18 mice/group), (D) % of JNK1 positive cells in the ARC ( n = 10 mice/group), (E) JNK1 immunoreactivity ( n = 8 mice/group), and (F) Jnk1 mRNA levels in the VMH ( n = 5–6 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test; ∗ P < 0.05, ∗∗ P < 0.01 and ∗∗∗ P < 0.001 vs. Jnk1 fl/fl 3 V: third ventricle. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article).

Article Snippet: The brain slices were permeabilized with 0.3% Triton X-100 in PBS, blocked with 10% goat serum in PBS, and incubated overnight at 4 °C with primary antibodies: anti-JNK1 (1:200, Sc-1648, Santa Cruz Biotechnology).

Techniques: Activity Assay, Control

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on energy balance. (A) Body weight ( n = 26–39 mice/group), (B–D) correlation between body length and body weight ( n = 7–11 mice group), (E) daily food intake ( n = 13–22 mice/group), (F) tissues weight ( n = 15–29 mice/group), (G) NMR analysis ( n = 6–9 mice/group), (H) energy expenditure (EE) during dark and light phases ( n = 6–9 mice/group, (I) cumulative EE ( n = 6–9 mice/group, (J) ANCOVA analysis of EE using body weight as a covariate ( n = 6–9 mice/group, (K) respiratory exchange ratio (RER) during dark and light phases ( n = 6–9 mice/group, (L) average RER ( n = 6–9 mice/group, and (M) spontaneous locomotor activity (LA) ( n = 6–9 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by two-way ANOVA ( H, K and M ), Linear regression ( B–D ), Mixed-effects model (A) , ANCOVA (J) or Student’s t-test (E, F, G, I, and L) ; ∗ P < 0.05 vs. Jnk1 fl/fl .

Article Snippet: The brain slices were permeabilized with 0.3% Triton X-100 in PBS, blocked with 10% goat serum in PBS, and incubated overnight at 4 °C with primary antibodies: anti-JNK1 (1:200, Sc-1648, Santa Cruz Biotechnology).

Techniques: Activity Assay

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on BAT thermogenesis. (A) Representative BAT thermographic images (scale bar: 1 cm), (B) temperature of BAT area ( n = 7–10 mice/group), (C) body temperature ( n = 5–8 mice/group), (D) representative immunoblot images, (E) densitometry quantification of UCP1 in BAT ( n = 5–8 mice/group), (F) representative UCP1 staining in the BAT (40X; scale bar: 200 μm), (G) BAT UCP1 stained area ( n = 6–8 mice/group), (H) adipocyte area ( n = 7–8 mice/group) and (I) norepinephrine (NE), dopamine (DA) and serotonin (5-HT) levels in BAT ( n = 8 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. In the western blot analyses values were expressed in relation to α-tubulin. Representative images for all proteins are shown, with all bands for each picture derived from the same gel. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test.

Article Snippet: The brain slices were permeabilized with 0.3% Triton X-100 in PBS, blocked with 10% goat serum in PBS, and incubated overnight at 4 °C with primary antibodies: anti-JNK1 (1:200, Sc-1648, Santa Cruz Biotechnology).

Techniques: Western Blot, Staining, Derivative Assay

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on glucose homeostasis. (A) Serum glucose levels ( n = 9–17 mice/group), (B) glucose tolerance test (GTT) ( n = 9–17 mice/group) and (C) area under the curve (AUC) ( n = 9–17 mice/group), (D) insulin tolerance test (ITT) ( n = 9–16 mice/group) and (E) AUC ( n = 9–16 mice/group), (F) pyruvate tolerance test (PTT) ( n = 6–9 mice/group) and (G) AUC ( n = 6–9 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by two-way ANOVA (B, D and F) or Student’s t-test (A, C, E, and G) ; ∗ P < 0.05, ∗∗ P < 0.01 and ∗∗∗ P < 0.001 vs. Jnk1 fl/fl ; ### P < 0.001 vs. Fed.

Article Snippet: The brain slices were permeabilized with 0.3% Triton X-100 in PBS, blocked with 10% goat serum in PBS, and incubated overnight at 4 °C with primary antibodies: anti-JNK1 (1:200, Sc-1648, Santa Cruz Biotechnology).

Techniques:

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on circulating and hepatic lipids. (A) Serum cholesterol levels ( n = 8 mice/group), (B) serum triglyceride levels ( n = 7–8 mice/group), (C) hepatic triglyceride levels ( n = 7 mice/group) (D) representative microphotographs of Oil-Red O-staining (40X; scale bar: 50 μm), (E) hepatic lipid content in Oil Red O-stained sections ( n = 6–7 mice/group) and (F) hepatic malondialdehyde (MDA) levels ( n = 6–7 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test. ∗ P < 0.05 and ∗∗ P < 0.01 vs. Jnk1 fl/fl . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article).

Article Snippet: The brain slices were permeabilized with 0.3% Triton X-100 in PBS, blocked with 10% goat serum in PBS, and incubated overnight at 4 °C with primary antibodies: anti-JNK1 (1:200, Sc-1648, Santa Cruz Biotechnology).

Techniques: Staining

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on fasting/refeeding and cold exposure challenges. (A) Body weight change ( n = 8–11 mice/group), (B and C) food intake ( n = 8–11 mice/group) and (D) serum glucose levels ( n = 8–11 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice subjected to a 24-hour fasting period and subsequent 24-hour refeeding. (E) Body weight change ( n = 8–11 mice/group; 4 out of 8 null mice died), (F) food intake ( n = 8–11 mice/group; 4 out of 8 null mice died), (G) body temperature change ( n = 8–11 mice/group; 4 out of 8 null mice died) and (H) % of survival ( n = 8–11 mice/group; 4 out of 8 null mice died) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice cold exposed by 14.5 h. Data are expressed as MEAN ± SEM. Statistical significance was determined by two-way ANOVA (A, B and D), Mixed-effects model (G) or Student’s t-test (C, E and F) .

Article Snippet: The brain slices were permeabilized with 0.3% Triton X-100 in PBS, blocked with 10% goat serum in PBS, and incubated overnight at 4 °C with primary antibodies: anti-JNK1 (1:200, Sc-1648, Santa Cruz Biotechnology).

Techniques:

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on the central T3 action on body weight and BAT thermogenesis. (A) Serum T4 ( n = 11 mice/group), (B) serum T3 ( n = 9 mice/group), (C and E) Body weight change (C: n = 7–8 mice/group; E: 8–12 mice/group), (D and F) daily food intake (D: n = 7–8 mice/group; F: 8–12 mice/group), (G and I) representative BAT thermographic images, (H and J) temperature of BAT area (H: n = 6–7 mice/group; J: 6–12 mice/group), (K and M) representative immunoblot images (L and N) densitometry quantification of UCP1 in BAT (L: n = 7–8 mice/group; N: 8–9 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice ICV treated with vehicle or T3. In the western blot analyses, values were expressed in relation to α-tubulin. Representative images for all proteins are shown, with all bands for each picture derived from the same gel, although they may be spliced for clarity (vertical black lines). Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test (A, B, D, F, H, J, L and N) or two-way ANOVA (C and E; ) or ∗ P < 0.05 and ∗∗ P < 0.01 vs. Jnk1 fl/fl .

Article Snippet: The brain slices were permeabilized with 0.3% Triton X-100 in PBS, blocked with 10% goat serum in PBS, and incubated overnight at 4 °C with primary antibodies: anti-JNK1 (1:200, Sc-1648, Santa Cruz Biotechnology).

Techniques: Western Blot, Derivative Assay

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on the central T3 action on hepatic lipids. (A and B) Hepatic triglyceride levels (A: n = 7–8 mice/group; B: n = 7–11 mice/group), (C and E) representative microphotographs of Oil-Red O-staining (40X; scale bar: 50 μm), (D and F) hepatic lipid content in Oil Red O-stained sections (D: n = 7 mice/group; F: n = 8–11 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice ICV treated with vehicle or T3. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test or two-way ANOVA . ∗ P < 0.05 vs. Jnk1 fl/fl . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article).

Article Snippet: The brain slices were permeabilized with 0.3% Triton X-100 in PBS, blocked with 10% goat serum in PBS, and incubated overnight at 4 °C with primary antibodies: anti-JNK1 (1:200, Sc-1648, Santa Cruz Biotechnology).

Techniques: Staining

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Genetic ablation of JNK1 in SF1 neurons. (A) Demonstration of Cre recombinase activity, as shown by the presence of red fluorescent td-Tomato in the VMH of t d-Tomato Sf1 Cre /Jnk1 fl/fl reporter mice but not control animals (20X; Scale bar: 100 μm). (B) Representative confocal images (40X; Scale bar: 100 μm). (C) % of JNK1 positive cells in the VMH ( n = 18 mice/group), (D) % of JNK1 positive cells in the ARC ( n = 10 mice/group), (E) JNK1 immunoreactivity ( n = 8 mice/group), and (F) Jnk1 mRNA levels in the VMH ( n = 5–6 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test; ∗ P < 0.05, ∗∗ P < 0.01 and ∗∗∗ P < 0.001 vs. Jnk1 fl/fl 3 V: third ventricle. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article).

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Activity Assay, Control

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on energy balance. (A) Body weight ( n = 26–39 mice/group), (B–D) correlation between body length and body weight ( n = 7–11 mice group), (E) daily food intake ( n = 13–22 mice/group), (F) tissues weight ( n = 15–29 mice/group), (G) NMR analysis ( n = 6–9 mice/group), (H) energy expenditure (EE) during dark and light phases ( n = 6–9 mice/group, (I) cumulative EE ( n = 6–9 mice/group, (J) ANCOVA analysis of EE using body weight as a covariate ( n = 6–9 mice/group, (K) respiratory exchange ratio (RER) during dark and light phases ( n = 6–9 mice/group, (L) average RER ( n = 6–9 mice/group, and (M) spontaneous locomotor activity (LA) ( n = 6–9 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by two-way ANOVA ( H, K and M ), Linear regression ( B–D ), Mixed-effects model (A) , ANCOVA (J) or Student’s t-test (E, F, G, I, and L) ; ∗ P < 0.05 vs. Jnk1 fl/fl .

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Activity Assay

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on BAT thermogenesis. (A) Representative BAT thermographic images (scale bar: 1 cm), (B) temperature of BAT area ( n = 7–10 mice/group), (C) body temperature ( n = 5–8 mice/group), (D) representative immunoblot images, (E) densitometry quantification of UCP1 in BAT ( n = 5–8 mice/group), (F) representative UCP1 staining in the BAT (40X; scale bar: 200 μm), (G) BAT UCP1 stained area ( n = 6–8 mice/group), (H) adipocyte area ( n = 7–8 mice/group) and (I) norepinephrine (NE), dopamine (DA) and serotonin (5-HT) levels in BAT ( n = 8 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. In the western blot analyses values were expressed in relation to α-tubulin. Representative images for all proteins are shown, with all bands for each picture derived from the same gel. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test.

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Western Blot, Staining, Derivative Assay

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on glucose homeostasis. (A) Serum glucose levels ( n = 9–17 mice/group), (B) glucose tolerance test (GTT) ( n = 9–17 mice/group) and (C) area under the curve (AUC) ( n = 9–17 mice/group), (D) insulin tolerance test (ITT) ( n = 9–16 mice/group) and (E) AUC ( n = 9–16 mice/group), (F) pyruvate tolerance test (PTT) ( n = 6–9 mice/group) and (G) AUC ( n = 6–9 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by two-way ANOVA (B, D and F) or Student’s t-test (A, C, E, and G) ; ∗ P < 0.05, ∗∗ P < 0.01 and ∗∗∗ P < 0.001 vs. Jnk1 fl/fl ; ### P < 0.001 vs. Fed.

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques:

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on circulating and hepatic lipids. (A) Serum cholesterol levels ( n = 8 mice/group), (B) serum triglyceride levels ( n = 7–8 mice/group), (C) hepatic triglyceride levels ( n = 7 mice/group) (D) representative microphotographs of Oil-Red O-staining (40X; scale bar: 50 μm), (E) hepatic lipid content in Oil Red O-stained sections ( n = 6–7 mice/group) and (F) hepatic malondialdehyde (MDA) levels ( n = 6–7 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test. ∗ P < 0.05 and ∗∗ P < 0.01 vs. Jnk1 fl/fl . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article).

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Staining

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on fasting/refeeding and cold exposure challenges. (A) Body weight change ( n = 8–11 mice/group), (B and C) food intake ( n = 8–11 mice/group) and (D) serum glucose levels ( n = 8–11 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice subjected to a 24-hour fasting period and subsequent 24-hour refeeding. (E) Body weight change ( n = 8–11 mice/group; 4 out of 8 null mice died), (F) food intake ( n = 8–11 mice/group; 4 out of 8 null mice died), (G) body temperature change ( n = 8–11 mice/group; 4 out of 8 null mice died) and (H) % of survival ( n = 8–11 mice/group; 4 out of 8 null mice died) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice cold exposed by 14.5 h. Data are expressed as MEAN ± SEM. Statistical significance was determined by two-way ANOVA (A, B and D), Mixed-effects model (G) or Student’s t-test (C, E and F) .

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques:

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on the central T3 action on body weight and BAT thermogenesis. (A) Serum T4 ( n = 11 mice/group), (B) serum T3 ( n = 9 mice/group), (C and E) Body weight change (C: n = 7–8 mice/group; E: 8–12 mice/group), (D and F) daily food intake (D: n = 7–8 mice/group; F: 8–12 mice/group), (G and I) representative BAT thermographic images, (H and J) temperature of BAT area (H: n = 6–7 mice/group; J: 6–12 mice/group), (K and M) representative immunoblot images (L and N) densitometry quantification of UCP1 in BAT (L: n = 7–8 mice/group; N: 8–9 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice ICV treated with vehicle or T3. In the western blot analyses, values were expressed in relation to α-tubulin. Representative images for all proteins are shown, with all bands for each picture derived from the same gel, although they may be spliced for clarity (vertical black lines). Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test (A, B, D, F, H, J, L and N) or two-way ANOVA (C and E; ) or ∗ P < 0.05 and ∗∗ P < 0.01 vs. Jnk1 fl/fl .

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Western Blot, Derivative Assay

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on the central T3 action on hepatic lipids. (A and B) Hepatic triglyceride levels (A: n = 7–8 mice/group; B: n = 7–11 mice/group), (C and E) representative microphotographs of Oil-Red O-staining (40X; scale bar: 50 μm), (D and F) hepatic lipid content in Oil Red O-stained sections (D: n = 7 mice/group; F: n = 8–11 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice ICV treated with vehicle or T3. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test or two-way ANOVA . ∗ P < 0.05 vs. Jnk1 fl/fl . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article).

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Staining

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Genetic ablation of JNK1 in SF1 neurons. (A) Demonstration of Cre recombinase activity, as shown by the presence of red fluorescent td-Tomato in the VMH of t d-Tomato Sf1 Cre /Jnk1 fl/fl reporter mice but not control animals (20X; Scale bar: 100 μm). (B) Representative confocal images (40X; Scale bar: 100 μm). (C) % of JNK1 positive cells in the VMH ( n = 18 mice/group), (D) % of JNK1 positive cells in the ARC ( n = 10 mice/group), (E) JNK1 immunoreactivity ( n = 8 mice/group), and (F) Jnk1 mRNA levels in the VMH ( n = 5–6 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test; ∗ P < 0.05, ∗∗ P < 0.01 and ∗∗∗ P < 0.001 vs. Jnk1 fl/fl 3 V: third ventricle. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article).

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Activity Assay, Control

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on energy balance. (A) Body weight ( n = 26–39 mice/group), (B–D) correlation between body length and body weight ( n = 7–11 mice group), (E) daily food intake ( n = 13–22 mice/group), (F) tissues weight ( n = 15–29 mice/group), (G) NMR analysis ( n = 6–9 mice/group), (H) energy expenditure (EE) during dark and light phases ( n = 6–9 mice/group, (I) cumulative EE ( n = 6–9 mice/group, (J) ANCOVA analysis of EE using body weight as a covariate ( n = 6–9 mice/group, (K) respiratory exchange ratio (RER) during dark and light phases ( n = 6–9 mice/group, (L) average RER ( n = 6–9 mice/group, and (M) spontaneous locomotor activity (LA) ( n = 6–9 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by two-way ANOVA ( H, K and M ), Linear regression ( B–D ), Mixed-effects model (A) , ANCOVA (J) or Student’s t-test (E, F, G, I, and L) ; ∗ P < 0.05 vs. Jnk1 fl/fl .

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Activity Assay

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on BAT thermogenesis. (A) Representative BAT thermographic images (scale bar: 1 cm), (B) temperature of BAT area ( n = 7–10 mice/group), (C) body temperature ( n = 5–8 mice/group), (D) representative immunoblot images, (E) densitometry quantification of UCP1 in BAT ( n = 5–8 mice/group), (F) representative UCP1 staining in the BAT (40X; scale bar: 200 μm), (G) BAT UCP1 stained area ( n = 6–8 mice/group), (H) adipocyte area ( n = 7–8 mice/group) and (I) norepinephrine (NE), dopamine (DA) and serotonin (5-HT) levels in BAT ( n = 8 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. In the western blot analyses values were expressed in relation to α-tubulin. Representative images for all proteins are shown, with all bands for each picture derived from the same gel. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test.

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Western Blot, Staining, Derivative Assay

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on glucose homeostasis. (A) Serum glucose levels ( n = 9–17 mice/group), (B) glucose tolerance test (GTT) ( n = 9–17 mice/group) and (C) area under the curve (AUC) ( n = 9–17 mice/group), (D) insulin tolerance test (ITT) ( n = 9–16 mice/group) and (E) AUC ( n = 9–16 mice/group), (F) pyruvate tolerance test (PTT) ( n = 6–9 mice/group) and (G) AUC ( n = 6–9 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by two-way ANOVA (B, D and F) or Student’s t-test (A, C, E, and G) ; ∗ P < 0.05, ∗∗ P < 0.01 and ∗∗∗ P < 0.001 vs. Jnk1 fl/fl ; ### P < 0.001 vs. Fed.

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques:

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on circulating and hepatic lipids. (A) Serum cholesterol levels ( n = 8 mice/group), (B) serum triglyceride levels ( n = 7–8 mice/group), (C) hepatic triglyceride levels ( n = 7 mice/group) (D) representative microphotographs of Oil-Red O-staining (40X; scale bar: 50 μm), (E) hepatic lipid content in Oil Red O-stained sections ( n = 6–7 mice/group) and (F) hepatic malondialdehyde (MDA) levels ( n = 6–7 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test. ∗ P < 0.05 and ∗∗ P < 0.01 vs. Jnk1 fl/fl . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article).

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Staining

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on fasting/refeeding and cold exposure challenges. (A) Body weight change ( n = 8–11 mice/group), (B and C) food intake ( n = 8–11 mice/group) and (D) serum glucose levels ( n = 8–11 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice subjected to a 24-hour fasting period and subsequent 24-hour refeeding. (E) Body weight change ( n = 8–11 mice/group; 4 out of 8 null mice died), (F) food intake ( n = 8–11 mice/group; 4 out of 8 null mice died), (G) body temperature change ( n = 8–11 mice/group; 4 out of 8 null mice died) and (H) % of survival ( n = 8–11 mice/group; 4 out of 8 null mice died) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice cold exposed by 14.5 h. Data are expressed as MEAN ± SEM. Statistical significance was determined by two-way ANOVA (A, B and D), Mixed-effects model (G) or Student’s t-test (C, E and F) .

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques:

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on the central T3 action on body weight and BAT thermogenesis. (A) Serum T4 ( n = 11 mice/group), (B) serum T3 ( n = 9 mice/group), (C and E) Body weight change (C: n = 7–8 mice/group; E: 8–12 mice/group), (D and F) daily food intake (D: n = 7–8 mice/group; F: 8–12 mice/group), (G and I) representative BAT thermographic images, (H and J) temperature of BAT area (H: n = 6–7 mice/group; J: 6–12 mice/group), (K and M) representative immunoblot images (L and N) densitometry quantification of UCP1 in BAT (L: n = 7–8 mice/group; N: 8–9 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice ICV treated with vehicle or T3. In the western blot analyses, values were expressed in relation to α-tubulin. Representative images for all proteins are shown, with all bands for each picture derived from the same gel, although they may be spliced for clarity (vertical black lines). Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test (A, B, D, F, H, J, L and N) or two-way ANOVA (C and E; ) or ∗ P < 0.05 and ∗∗ P < 0.01 vs. Jnk1 fl/fl .

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Western Blot, Derivative Assay

Journal: Molecular Metabolism

Article Title: JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism

doi: 10.1016/j.molmet.2025.102170

Figure Lengend Snippet: Effect of loss of JNK1 in SF1 neurons on the central T3 action on hepatic lipids. (A and B) Hepatic triglyceride levels (A: n = 7–8 mice/group; B: n = 7–11 mice/group), (C and E) representative microphotographs of Oil-Red O-staining (40X; scale bar: 50 μm), (D and F) hepatic lipid content in Oil Red O-stained sections (D: n = 7 mice/group; F: n = 8–11 mice/group) of Jnk1 fl/fl and Sf1 Cre /Jnk1 fl/fl mice ICV treated with vehicle or T3. Data are expressed as MEAN ± SEM. Statistical significance was determined by Student’s t-test or two-way ANOVA . ∗ P < 0.05 vs. Jnk1 fl/fl . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article).

Article Snippet: To generate SF1 neuron-specific JNK1 knockout mice ( Sf1 Cre /Jnk1 fl/fl ), SF1-Cre mice (Tg( Nr5a1 -Cre)Lowl/J; The Jackson Laboratory) [ , , ] were crossed with JNK1 floxed mice ( Jnk1 fl/fl ; Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) [ ].

Techniques: Staining