Journal: Frontiers in Endocrinology

Article Title: Fibroblast Growth Factor 21-Null Mice Do Not Exhibit an Impaired Response to Fasting

doi: 10.3389/fendo.2016.00077

Figure Lengend Snippet: FGF21 is primarily expressed in the liver and is dispensable for the physiological response to fasting . WT and FGF21KO animals were either allowed ad libidum access to food (fed) or subjected to a 24-h fast (fasted). (A) Plasma FGF21 levels were measured in WT animals. (B) FGF21 mRNA and (C) protein expression were measured in liver and adipose tissue from WT animals. (D) Blood glucose was assessed via glucometer in each cohort. Plasma was collected from WT and FGF21KO animals and used to determine circulating levels of (E) insulin, (F) βHB, (G) triglycerides, and (H) free fatty acids. The concentration of (I) triglycerides and (J) glycogen was measured in the livers of WT and FGF21KO animals. (K) A pyruvate tolerance test was performed on a separate cohort of WT and FGF21KO animals by administration of 2 g/kg sodium pyruvate following a 22-h fast. * p < 0.05 vs. fed; α, p < 0.05 vs. WT Fed; β, p < 0.05 vs. FGF21KO fed; φ, p < 0.05 vs. WT fasted; #, p < 0.05 vs. WT. No statistical difference was observed in fed measurements between genotypes.

Article Snippet: Male C57Bl/6J and FGF21 knockout (FGF21KO) mice (Taconic Farms) were maintained on a standard chow diet consisting of 13% fat, 67% carbohydrate, and 20% protein caloric content (2014; Harlan Teklad, Madison, WI, USA) and had free access to food and water before randomization by weight.

Techniques: Clinical Proteomics, Expressing, Concentration Assay

Journal: Frontiers in Endocrinology

Article Title: Fibroblast Growth Factor 21-Null Mice Do Not Exhibit an Impaired Response to Fasting

doi: 10.3389/fendo.2016.00077

Figure Lengend Snippet: Oxidative and gluconeogenic gene expression is attenuated in the liver, while lipase gene expression and activity in WAT remains unaltered in fasted FGF21KO mice . (A) In the liver, expressions of genes associated with fatty acid oxidation (CPT1a, ACADS, ACADM, ACADL, ACADVL, HADH), fatty acid import (CD36), gluconeogenesis (G6PC, PCK1), and ketone body production (HMGCS2, BDH1) were measured. (B) Expressions of genes associated with lipolysis (HSL, ATGL, LPL), fatty acid synthesis (FASN), fatty acid import (CD36), and thermogenesis (CIDEA, UCP1) were measured. In adipose tissue: α, p < 0.05 vs. WT Fed; β, p < 0.05 vs. FGF21KO fed; φ, p < 0.05 vs. WT fasted. No statistical differences were observed between genotypes in fed expression of any gene measured. (C) The amount of total and phosphorylated HSL was assessed by Western blot in WAT of WT and FGF21KO animals in both the fed and fasted state.

Article Snippet: Male C57Bl/6J and FGF21 knockout (FGF21KO) mice (Taconic Farms) were maintained on a standard chow diet consisting of 13% fat, 67% carbohydrate, and 20% protein caloric content (2014; Harlan Teklad, Madison, WI, USA) and had free access to food and water before randomization by weight.

Techniques: Gene Expression, Activity Assay, Expressing, Western Blot

Journal: Frontiers in Endocrinology

Article Title: Fibroblast Growth Factor 21-Null Mice Do Not Exhibit an Impaired Response to Fasting

doi: 10.3389/fendo.2016.00077

Figure Lengend Snippet: Endogenous FGF21 is not required for proper lipid and carbohydrate metabolism during the fed to fasted transition . At the beginning of the light cycle, WT animals had their food removed and were administered 5 mg/kg ΔN17 once every 3 h for 12 h. (A) Blood glucose measurements were taken via glucometer at the specified time points. Circulating levels of (B) insulin, (C) βHB, (D) triglycerides, and (E) free fatty acids were determined from plasma samples collected at the end of the study. Liver samples were taken at the end of the study and used to determine the concentrations of (F) triglycerides and (G) glycogen. (H) In the liver, expression of FGF21 as well as genes associated with fatty acid oxidation (CPT1a, ACADS, ACADM, ACADL, ACADVL, HADH), fatty acid import (CD36), gluconeogenesis (G6PC, PCK1), and ketone body production (HMGCS2, BDH1) were measured. (I) Expression of FGF21 in addition to genes associated with lipolysis (HSL, ATGL, LPL), fatty acid synthesis (FASN), fatty acid import (CD36), and thermogenesis (CIDEA, UCP1) were measured in adipose tissue. * p < 0.05 vs. PBS.

Article Snippet: Male C57Bl/6J and FGF21 knockout (FGF21KO) mice (Taconic Farms) were maintained on a standard chow diet consisting of 13% fat, 67% carbohydrate, and 20% protein caloric content (2014; Harlan Teklad, Madison, WI, USA) and had free access to food and water before randomization by weight.

Techniques: Clinical Proteomics, Expressing

Journal: Frontiers in Endocrinology

Article Title: Fibroblast Growth Factor 21-Null Mice Do Not Exhibit an Impaired Response to Fasting

doi: 10.3389/fendo.2016.00077

Figure Lengend Snippet: Blockade of FGF21 signaling during late fasting does not impair the fasted response . WT mice were fasted for 21 h, administered 5 mg/kg ΔN17, and then subjected to a PTT 1 h later by administration of 2 g/kg sodium pyruvate. (A) Blood glucose was measured at the specified time points via glucometer. A separate cohort of WT mice was fasted for 23 h, administered 5 mg/kg ΔN17, and then sacrificed 1 h later. (B) Blood glucose was assessed via glucometer. Plasma samples were collected and used to determine circulating levels of (C) insulin, (D) βHB, (E) triglycerides, and (F) free fatty acids. Hepatic (G) Triglyceride and (H) glycogen content was measured. (I) In the liver, expression of FGF21 as well as genes associated with fatty acid oxidation (CPT1a, ACADS, ACADM, ACADL, ACADVL, HADH), fatty acid import (CD36), gluconeogenesis (G6PC, PCK1), and ketone body production (HMGCS2, BDH1) were measured. (J) Expression of FGF21 in addition to genes associated with lipolysis (HSL, ATGL, LPL), fatty acid synthesis (FASN), fatty acid import (CD36), and thermogenesis (CIDEA, UCP1) were measured in adipose tissue. * p < 0.05 vs. PBS.

Article Snippet: Male C57Bl/6J and FGF21 knockout (FGF21KO) mice (Taconic Farms) were maintained on a standard chow diet consisting of 13% fat, 67% carbohydrate, and 20% protein caloric content (2014; Harlan Teklad, Madison, WI, USA) and had free access to food and water before randomization by weight.

Techniques: Clinical Proteomics, Expressing

Journal: PLOS One

Article Title: Methionine restriction provides sex-specific protection against high-fat diet-induced adiposity, peripheral insulin resistance, and neuroinflammation in FGF21-dependent and independent manners in mice

doi: 10.1371/journal.pone.0343503

Figure Lengend Snippet: Hepatic and circulating fibroblast growth factor 21 (FGF21).

Article Snippet: Breeding pairs of male and female wild-type (WT, Jax#000664) and Fgf21 knockout ( Fgf21 -/- , Jax#033846) mice purchased from the Jackson Laboratory (Bar Harbor, ME).

Techniques:

Journal: PLOS One

Article Title: Methionine restriction provides sex-specific protection against high-fat diet-induced adiposity, peripheral insulin resistance, and neuroinflammation in FGF21-dependent and independent manners in mice

doi: 10.1371/journal.pone.0343503

Figure Lengend Snippet: Hepatic insulin signaling in fibroblast growth factor 21 knockout ( Fgf21 -/- ) males.

Article Snippet: Breeding pairs of male and female wild-type (WT, Jax#000664) and Fgf21 knockout ( Fgf21 -/- , Jax#033846) mice purchased from the Jackson Laboratory (Bar Harbor, ME).

Techniques: Knock-Out

Journal: PLOS One

Article Title: Methionine restriction provides sex-specific protection against high-fat diet-induced adiposity, peripheral insulin resistance, and neuroinflammation in FGF21-dependent and independent manners in mice

doi: 10.1371/journal.pone.0343503

Figure Lengend Snippet: Hepatic insulin signaling in fibroblast growth factor 21 knockout ( Fgf21 -/- ) females.

Article Snippet: Breeding pairs of male and female wild-type (WT, Jax#000664) and Fgf21 knockout ( Fgf21 -/- , Jax#033846) mice purchased from the Jackson Laboratory (Bar Harbor, ME).

Techniques: Knock-Out

Journal: PLOS One

Article Title: Methionine restriction provides sex-specific protection against high-fat diet-induced adiposity, peripheral insulin resistance, and neuroinflammation in FGF21-dependent and independent manners in mice

doi: 10.1371/journal.pone.0343503

Figure Lengend Snippet: Hypothalamic insulin signaling in fibroblast growth factor 21 knockout ( Fgf21 -/- ) males.

Article Snippet: Breeding pairs of male and female wild-type (WT, Jax#000664) and Fgf21 knockout ( Fgf21 -/- , Jax#033846) mice purchased from the Jackson Laboratory (Bar Harbor, ME).

Techniques: Knock-Out

Journal: PLOS One

Article Title: Methionine restriction provides sex-specific protection against high-fat diet-induced adiposity, peripheral insulin resistance, and neuroinflammation in FGF21-dependent and independent manners in mice

doi: 10.1371/journal.pone.0343503

Figure Lengend Snippet: Hypothalamic insulin signaling in fibroblast growth factor 21 knockout ( Fgf21 -/- ) females.

Article Snippet: Breeding pairs of male and female wild-type (WT, Jax#000664) and Fgf21 knockout ( Fgf21 -/- , Jax#033846) mice purchased from the Jackson Laboratory (Bar Harbor, ME).

Techniques: Knock-Out

Journal: Cell death & disease

Article Title: FGF21-FGFR1 controls mitochondrial homeostasis in cardiomyocytes by modulating the degradation of OPA1.

doi: 10.1038/s41419-023-05842-9

Figure Lengend Snippet: Fig. 1 16-week-old FGF21 KO mice developed diastolic dysfunction, mild cardiac hypertrophy, and fibrosis. A Representative 16-week WT and FGF21 KO mice echocardiography images of vectors of wall trace tendency calculated by Vevo Software. B Representative 16-week WT and FGF21 KO mice echocardiography images of vectors of radial and longitudinal strain calculated by Vevo Software. C 16-week WT and FGF21 KO mice left ventricular global longitudinal strain (GLS) was calculated by Vevo Software. n = 5 mice. D Representative cross-sections of heart stained for WGA, and Sirius red in 16-week WT and FGF21 KO mice heart tissue. E Quantitative analysis of cardiomyocyte size (WGA staining), fibrotic area (red area in Sirius red staining). n = 5 mice. F Relative mRNA levels of hypertrophic and fibrotic genes in the 16-week WT and FGF21 KO mice heart. n = 5 mice. G, H Ejection fraction and GLS were measured by echocardiography every 8 weeks (every 2 weeks in 16–24 week, every 4 weeks in 48–56 week) in WT and FGF21 KO mice. n = 5 mice. Data are expressed as the mean ± SEM, with individual data points. Data were analyzed by two-tailed unpaired Student’s test (C, E, F), two-way RM ANOVA with Geisser-Greenhouse’s correction (G, H).

Article Snippet: FGF21 knockout mice in C57BL/6J background purchased from Cyagen Biosciences (Suzhou, China), which is conventional knockout type.

Techniques: Software, Staining, Two Tailed Test

Journal: Molecular Metabolism

Article Title: Combined genetic deletion of GDF15 and FGF21 has modest effects on body weight, hepatic steatosis and insulin resistance in high fat fed mice

doi: 10.1016/j.molmet.2022.101589

Figure Lengend Snippet: Key resources table

Article Snippet: Mouse FGF21 was analysed using a Quantikine ELISA kit (R&D Systems, product code MF2100) following the manufacturer’s instructions.

Techniques: Paraffin Wax, SYBR Green Assay, Enzyme-linked Immunosorbent Assay, Modification, RNAscope, Polymer, TaqMan Assay, Control, Isolation, Homogenization, Sterility, Tissue Homogenization, Imaging, Recombinant, Sequencing, Software, Real-time Polymerase Chain Reaction

Journal: Molecular Metabolism

Article Title: Combined genetic deletion of GDF15 and FGF21 has modest effects on body weight, hepatic steatosis and insulin resistance in high fat fed mice

doi: 10.1016/j.molmet.2022.101589

Figure Lengend Snippet: Phenotypic characterization of GDF15 knockout mice on a high fat diet (HFD) . (A and B) Body weight and percent body weight gain of wild type (WT) and GDF15 KO mice fed a 60% HFD; Inset, final body weight and percent body weight gain. (C) Weight of epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (scWAT), liver and brown adipose tissue (BAT), harvested at the end of the study, 25 weeks of HFD (n = 13,9). (D) Weight of total hepatic lipids in g; total lipid extracted from 25 mg tissue was normalized to total liver weight (n = 14,9). (E) Lipid droplet area (Percent liver area) determined from histological analyses of haematoxylin/eosin (H&E) stained liver sections (n = 9,8). (F) Plasma triglycerides (TG), cholesterol, leptin, alanine transaminase (ALT) and aspartate transaminase (AST) from random fed mice after 16 weeks of HFD-feeding (n = 12,11). (G) Blood glucose, plasma insulin and HOMA-IR levels from 6 h fasted mice, after 16 weeks of HFD feeding (n = 16–29). (H and I) Blood glucose levels during intraperitoneal (ip) glucose tolerance test (GTT) and percent change from initial blood glucose levels during insulin tolerance test (ITT) after 16 weeks of HFD feeding. Inset, area under the curve analysis of glucose over time. (J) Plasma FGF21 levels from random fed mice at 16 weeks of HFD feeding (n = 7,9). (K) FGF21 mRNA expression in tissues from WT and GDF15 KO mice after 25 weeks HFD feeding (n = 8–11). All data are means ± S.D ∗/∗∗/∗∗∗/∗∗∗∗ - p < 0.05/0.01/0.001/0.0001.

Article Snippet: Mouse FGF21 was analysed using a Quantikine ELISA kit (R&D Systems, product code MF2100) following the manufacturer’s instructions.

Techniques: Knock-Out, Staining, Clinical Proteomics, Expressing

Journal: Molecular Metabolism

Article Title: Combined genetic deletion of GDF15 and FGF21 has modest effects on body weight, hepatic steatosis and insulin resistance in high fat fed mice

doi: 10.1016/j.molmet.2022.101589

Figure Lengend Snippet: GDF15 mRNA expression within high fat diet fed mouse and human adipose tissue . (A) In situ hybridization analysis of GDF15 mRNA (red) from 18-week-old high fat diet (HFD) fed wild type (WT) mouse epididymal adipose tissue. Black arrows indicate GDF15 staining in foamy macrophages contributing to the formation of ‘crown-like structures’. Blue arrow indicates GDF15 staining within adipocytes. (B) Representative haematoxylin/eosin image of epididymal tissue from 18-week old HFD fed WT mouse. Black arrows indicate infiltrating cells. (C) Representative image (corresponding to the image in B) of epididymal tissue from 18-week-old HFD fed WT mouse stained with the macrophage marker F4/80 confirming that the cells contributing to the ‘crown like structures’ are macrophages. (D and E) GDF15 and EMR1 mRNA expression from 14 week old Chow or HFD fed WT mouse epididymal tissue fractionated into adipocytes, CD11b negative (−) and CD11b positive (+) stromal vascular fractions (SVF) (n = 3–4). (F) Correlation of GDF15 expression with EMR1 expression in epididymal tissue from 14 week Chow or HFD fed wild type mice (n = 8). (G–I) Human subcutaneous adipose tissue GDF15 gene expression levels in the TwinsUK adipose study associated with estimated macrophage proportion in adipose tissue (G), and macrophage markers CD68 and EMR1 (H and I). Each point represents data from a single individual. Plotted gene expression residuals of GDF15, CD68 and EMR1 were adjusted for age, BMI and RNA-Seq technical covariates. (J and K) GDF15 gene expression levels in the ‘Obese study’ associated with macrophage marker CD68 in human subcutaneous and visceral adipose tissue. (L and M) In situ hybridization analysis of Gdf15 mRNA (red) from 18-week old HFD fed WT mouse liver and brown adipose tissue. (N) FGF21 mRNA expression from 14 week Chow or HFD fed WT mouse epididymal tissue fractionated in to adipocytes, CD11b negative (−) and CD11b positive (+) stromal vascular fraction (SVF) (n = 3–4).

Article Snippet: Mouse FGF21 was analysed using a Quantikine ELISA kit (R&D Systems, product code MF2100) following the manufacturer’s instructions.

Techniques: Expressing, In Situ Hybridization, Staining, Marker, Gene Expression, RNA Sequencing

Journal: Molecular Metabolism

Article Title: Combined genetic deletion of GDF15 and FGF21 has modest effects on body weight, hepatic steatosis and insulin resistance in high fat fed mice

doi: 10.1016/j.molmet.2022.101589

Figure Lengend Snippet: Phenotypic characterization of LysM-Cre mediated GDF15 macrophage knockout mouse on a high fat diet (HFD) . (A) GDF15 mRNA expression from 24-week-old high fat diet (HFD) fed wild type (WT) and LysM-GDF15 KO mouse epididymal adipose tissue fractionated into adipocytes and CD11b positive (+) stromal vascular fraction (SVF) (n = 4). (B) GDF15 mRNA expression in tissues from 24 week HFD fed WT and LysM-GDF15 KO mice. Epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (scWAT), brown adipose tissue (BAT), liver and kidney (n = 4–7). (C) Plasma GDF15 levels from random fed mice at indicated weeks on HFD (n = 15–18). (D) FGF21 mRNA expression in tissues from 24-week HFD fed WT and LysM-GDF15 KO mice (n = 4–7). (E) Plasma FGF21 levels from random fed mice at indicated weeks on HFD (n = 11–18). (F and G) Body weight and percent body weight gain of WT and LysM-GDF15 KO mice fed a 60% HFD; Inset, final body weight and percent body weight gain. (H) Weight of epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (scWAT), liver and brown adipose tissue (BAT) harvested at the end of the study, 24 weeks of HFD (n = 16–18). (I) Weight of total hepatic lipids in g; total lipid extracted from 25 mg tissue was normalized to total liver weight (n = 16,17). (J) Plasma leptin levels in mice from random fed mice after 16 weeks HFD-feeding (n = 16–18). (K) Blood glucose, plasma insulin and HOMA-IR levels from 6 h fasted mice, after 16 weeks of HFD feeding (n = 16,18). (L and M) Blood glucose levels during ip glucose tolerance test (GTT) and percent change from initial blood glucose levels during insulin tolerance test (ITT) after 16 weeks of HFD feeding. Inset, area under the curve analysis of glucose over time. (N) Plasma triglycerides (TG), cholesterol, alanine transaminase (ALT) and aspartate transaminase (AST) from random fed mice, after 16 weeks of HFD feeding (n = 9–11). All data are means ± S.D ∗/∗∗ - p < 0.05/0.01.

Article Snippet: Mouse FGF21 was analysed using a Quantikine ELISA kit (R&D Systems, product code MF2100) following the manufacturer’s instructions.

Techniques: Knock-Out, Expressing, Clinical Proteomics

Journal: Molecular Metabolism

Article Title: Combined genetic deletion of GDF15 and FGF21 has modest effects on body weight, hepatic steatosis and insulin resistance in high fat fed mice

doi: 10.1016/j.molmet.2022.101589

Figure Lengend Snippet: Phenotypic characterization of bone marrow deleted GDF15 knockout mouse on a high fat diet . (A) GDF15 mRNA expression in tissues from 24-week old high fat diet (HFD) fed WT and BMT-GDF15 KO mice. Epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (scWAT) and brown adipose tissue (BAT) (n = 8–12). (B) Plasma GDF15 levels from random fed mice at the onset (week 0) and after 12 weeks of HFD feeding (n = 12). (C) FGF21 mRNA expression from indicated tissues of 24 week HFD fed WT and BMT-GDF15 KO mice (n = 8–12). (D) Plasma FGF21 levels from random fed mice at the onset (week 0) and after 12 weeks of HFD feeding (n = 12). (E and F) Body weight and percent body weight gain of WT and BMT-GDF15 KO mice fed a 60% HFD; Inset, final body weight and percent body weight gain. (G) Weight of epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (scWAT), liver and brown adipose tissue (BAT) harvested at the end of the study, 24 weeks of HFD (n = 3–12). (H) Plasma triglycerides (TG), cholesterol, leptin, alanine transaminase (ALT) and aspartate transaminase (AST) from random fed mice, after 16 weeks of HFD feeding (n = 12). (I) Weight of total hepatic lipids in g; total lipid extracted from 25 mg tissue was normalized to total liver weight (n = 12). (J) Blood glucose, plasma insulin and HOMA-IR levels from 6 h fasted mice after 16 weeks of HFD feeding (n = 7,6). (K and L) Blood glucose levels during ip glucose tolerance test (GTT) and percent change from initial blood glucose levels during insulin tolerance test (ITT) after 16 weeks of HFD feeding. Inset, area under the curve analysis of glucose over time. All data are means ± S.D ∗/∗∗/∗∗∗/∗∗∗∗ - p < 0.05/0.01/0.001/0.0001.

Article Snippet: Mouse FGF21 was analysed using a Quantikine ELISA kit (R&D Systems, product code MF2100) following the manufacturer’s instructions.

Techniques: Knock-Out, Expressing, Clinical Proteomics

Journal: Molecular Metabolism

Article Title: Combined genetic deletion of GDF15 and FGF21 has modest effects on body weight, hepatic steatosis and insulin resistance in high fat fed mice

doi: 10.1016/j.molmet.2022.101589

Figure Lengend Snippet: Phenotypic characterization of Alb-Cre mediated GDF15 hepatocyte knockout mouse on a high fat diet . (A) GDF15 mRNA expression in tissues from 24-week old high fat diet (HFD) fed wild type (WT) and Alb-GDF15 KO mice. Epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (scWAT), liver, brown adipose tissue (BAT) and kidney (n = 10–16). (B) Plasma GDF15 levels from random fed mice at the onset (week 0) and after 12 weeks of HFD feeding (n = 15,13). (C) FGF21 mRNA expression in indicated tissues from 24-week HFD fed WT and Alb-GDF15 KO mice (n = 10–13). (D) Plasma FGF21 levels from random fed mice at the onset (week 0) and after 12 weeks of HFD feeding (n = 15,13). (E and F) Body weight and percent body weight gain of WT and Alb-GDF15 KO mice fed a 60% HFD; Inset, final body weight and percent body weight gain. (G) Weight of epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (scWAT), liver and brown adipose tissue (BAT) harvested at the end of the study, 24 weeks of HFD (n = 15,11). (H) Plasma leptin, triglycerides (TG), cholesterol, alanine transaminase (ALT) and aspartate transaminase (AST) from random fed mice, after 16 weeks of HFD feeding (n = 15,13). (I) Weight of total hepatic lipids in g; total lipid extracted from 25 mg tissue was normalized to total liver weight (n = 15,16). (J and K) Blood glucose levels during ip glucose tolerance test (GTT) and percent change from initial blood glucose levels during insulin tolerance test (ITT) after 16 weeks of HFD feeding. Inset, area under the curve analysis of glucose over time. (L) Blood glucose, plasma insulin and HOMA-IR levels from 6 h fasted mice, after 16 weeks of HFD feeding (n = 14,13). All data are means ± S.D ∗/∗∗/∗∗∗/∗∗∗∗ - p < 0.05/0.01/0.001/0.0001.

Article Snippet: Mouse FGF21 was analysed using a Quantikine ELISA kit (R&D Systems, product code MF2100) following the manufacturer’s instructions.

Techniques: Knock-Out, Expressing, Clinical Proteomics

Journal: Molecular Metabolism

Article Title: Combined genetic deletion of GDF15 and FGF21 has modest effects on body weight, hepatic steatosis and insulin resistance in high fat fed mice

doi: 10.1016/j.molmet.2022.101589

Figure Lengend Snippet: Phenotypic characterization of dKO knockout mice on a high fat diet . (A) Liver GDF15 and (B) FGF21 mRNA expression from 24-week-old high fat diet (HFD) fed WT, FGF21 KO, GDF15 KO and FGF21/GDF15 double knockout (dKO) mice (n = 5). (C and D) Plasma GDF15 and FGF21 from random fed mice at indicated time after high fat feeding (n = 3–11). (E and F) Body weight and percent body weight gain of WT, FGF21 KO, GDF15 KO and dKO mice fed a 60% HFD; Inset, final body weight and percent body weight gain. (G and H) Blood glucose levels during ip glucose tolerance test (GTT) and percent change from initial blood glucose levels during insulin tolerance test (ITT) after 16 weeks of HFD feeding. Inset, area under the curve analysis of glucose over time. (I) Blood glucose, plasma insulin and HOMA-IR levels from 6 h fasted mice after 16 weeks of HFD feeding (n = 19–29). (J) Weight of epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (scWAT), liver and brown adipose tissue (BAT) harvested at the end of the study, 24 weeks of HFD (n = 11–17). (K) Weight of total hepatic lipids; total lipid extracted from 25 mg tissue was normalized to total liver weight (n = 9–17). (L) Lipid droplet area (Percent liver area) determined from histological analyses of H&E stained liver sections (n = 8–11). (M) Plasma triglycerides (TG) from random fed mice, after 24 weeks of HFD feeding (n = 8). (N) Hepatic mRNA expression of genes involved in lipid metabolism (n = 9–17). All data are means ± S.D ∗/∗∗/∗∗∗/∗∗∗∗ - p < 0.05/0.01/0.001/0.0001. Please note that the data for WT and GDF15KO overlaps with the data presented in Figure 1 .

Article Snippet: Mouse FGF21 was analysed using a Quantikine ELISA kit (R&D Systems, product code MF2100) following the manufacturer’s instructions.

Techniques: Knock-Out, Expressing, Double Knockout, Clinical Proteomics, Staining

Journal: PLOS One

Article Title: Methionine restriction provides sex-specific protection against high-fat diet-induced adiposity, peripheral insulin resistance, and neuroinflammation in FGF21-dependent and independent manners in mice

doi: 10.1371/journal.pone.0343503

Figure Lengend Snippet: Hepatic insulin signaling in wild-type (WT) males.

Article Snippet: Breeding pairs of male and female wild-type (WT, Jax#000664) and Fgf21 knockout ( Fgf21 -/- , Jax#033846) mice purchased from the Jackson Laboratory (Bar Harbor, ME).

Techniques:

Journal: PLOS One

Article Title: Methionine restriction provides sex-specific protection against high-fat diet-induced adiposity, peripheral insulin resistance, and neuroinflammation in FGF21-dependent and independent manners in mice

doi: 10.1371/journal.pone.0343503

Figure Lengend Snippet: Hepatic insulin signaling in wild-type (WT) females.

Article Snippet: Breeding pairs of male and female wild-type (WT, Jax#000664) and Fgf21 knockout ( Fgf21 -/- , Jax#033846) mice purchased from the Jackson Laboratory (Bar Harbor, ME).

Techniques:

Journal: PLOS One

Article Title: Methionine restriction provides sex-specific protection against high-fat diet-induced adiposity, peripheral insulin resistance, and neuroinflammation in FGF21-dependent and independent manners in mice

doi: 10.1371/journal.pone.0343503

Figure Lengend Snippet: Hypothalamic insulin signaling in wild-type (WT) males.

Article Snippet: Breeding pairs of male and female wild-type (WT, Jax#000664) and Fgf21 knockout ( Fgf21 -/- , Jax#033846) mice purchased from the Jackson Laboratory (Bar Harbor, ME).

Techniques:

Journal: PLOS One

Article Title: Methionine restriction provides sex-specific protection against high-fat diet-induced adiposity, peripheral insulin resistance, and neuroinflammation in FGF21-dependent and independent manners in mice

doi: 10.1371/journal.pone.0343503

Figure Lengend Snippet: Hypothalamic insulin signaling in wild-type (WT) females.

Article Snippet: Breeding pairs of male and female wild-type (WT, Jax#000664) and Fgf21 knockout ( Fgf21 -/- , Jax#033846) mice purchased from the Jackson Laboratory (Bar Harbor, ME).

Techniques:

Journal: International journal of obesity (2005)

Article Title: Optimizing adipogenic cocktail composition to enhance beige adipogenesis and evaluate thermogenic potential in primary mouse subcutaneous fat cell cultures

doi: 10.1038/s41366-025-01946-8

Figure Lengend Snippet: a–c Analysis in whole-body Fgf21 KO mice. a qPCR analysis of Fgf21 mRNA levels in inguinal white adipose tissue (IWAT) from wild-type (WT) control and Fgf21 KO mice ( n = 6/genotype). b qPCR analysis of thermogenic ( Ucp1 ) and adipogenic markers ( Adipoq and Fabp4 ) in inguinal preadipocytes and mature adipocytes differentiated using adipogenic recipes R1, R2, R3, and R4 ( n = 6–8/group). c qPCR analysis of thermogenic ( Ucp1, Ppargc1a, and Cox8b ) and adipogenic ( Adipoq, Fabp4, and Pparg ) gene expression in fully differentiated inguinal mature adipocytes using different adipogenic recipes (R1, n = 5–6; R2, n = 6; R3, n = 5–6; R4, n = 6). d , e Analysis in fat-specific Prdm16 KO mice. d Top: Schematic representation of fat-specific Prdm16 KO generation by crossing Prdm16 fl/fl and Adipoq -Cre mice (created with BioRender.com ). Bottom: qPCR analysis of Prdm16 gene expression in IWAT from floxed control and KO mice ( n = 6/genotype). e qPCR analysis of thermogenic and adipogenic markers in inguinal preadipocytes and mature adipocytes differentiated using adipogenic recipes R3 ( n = 8–10/group) and R4 ( n = 8–12/group). f , g Analysis in UM-HET3 mice. f Left: Schematic of UM-HET3 mouse generation via a four-way cross, achieved by mating CByB6F1/J hybrid females with C3D2F1/J hybrid males (created with BioRender.com ). Right: qPCR analysis of thermogenic and adipogenic markers in inguinal preadipocytes and mature adipocytes differentiated using adipogenic recipes R3 ( n = 4–8/group) and R4 ( n = 6–8/group). g Representative images of (top) Oil Red O and (bottom) BODIPY and DAPI-stained mature inguinal adipocytes differentiated using adipogenic recipes R3 and R4. Scale bar: 500 μm. Data are presented as mean ± SEM. Four-group comparisons were assessed by one-way ANOVA with Tukey’s post hoc test, Welch’s ANOVA with Dunnett’s T3, or Kruskal–Wallis test with Dunn’s post hoc test. Different letters indicate statistically significant differences at p < 0.05. n.s., not significant.

Article Snippet: Wild-type C57BL/6J (Stock #000664), PR/SET domain 16 floxed ( Prdm16 fl/fl ) (Stock #024992), Adiponectin ( Adipoq )-Cre (Stock #028020), CByB6F1/J (Stock # 100009), C3D2F1/J (Stock #100004), and fibroblast growth factor 21 ( Fgf21 ) knockout (KO) (Stock #033846) mice were obtained from Jackson Laboratory (Bar Harbor, MN, USA).

Techniques: Control, Gene Expression, Staining