Fibroblast Growth Factor 21 Levels Research Articles

The effects of Hibiscus sabdariffa Linn. on the levels of FGF21 and AMPK in the Heart of Diabetic Mice

Background : Diabetes Mellitus (DM) is a metabolic disorder characterized by pancreatic cell dysfunction and insulin resistance. Fibroblast Growth Factor 21 (FGF21) is thought to have a cardioprotective role. Through FGF21 signaling, AMP-activated protein kinase (AMPK) activity reduces apoptosis, inflammation, hypertrophy, and fibrosis in the heart. Hibiscus sabdariffa Linn. (HSL) contains flavonoids that have hypoglycemic effects and are anti-inflammatory and antioxidant-active. This study aims to assess the effect of HSL on FGF21 and AMPK levels in the heart of diabetic mice models. Methods : An experimental study using Deutschland Denken Yoken (DDY) mice aged eight weeks were divided into four groups: Control, DM Control, HSL 200, and HSL 400. In the DM control, HSL 200, and HSL 400 groups, diabetes was induced by giving a High Fat Diet(HFD) and STZ 40mg/kgbb. The HSL 200 group was given HSL 200mg/kgBB supplementation for three weeks, and the HSL 400 group was given HSL 400 mg/kgBB supplementation for three weeks. FGF21 and AMPK levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Results : There was no significant difference between FGF21 and AMPK levels between the control and DM control groups. FGF21 and AMPK levels in the HSL 400 group were higher than in the control, DM control, and HSL 200 groups. Conclusions : These findings suggest that HSL supplementation at specific doses can potentially increase the activation of FGF 21 and AMPK signaling in the heart of diabetic mice models.

Evaluating Fibroblast Growth Factor 21 (FGF21) Levels Post-Gastric Sleeve Surgery in Obese Patients.

Background and objectives Obesity is a major global health concern linked with increased risk of chronic diseases. This study aimed to assess the levels of fibroblast growth factor 21 (FGF21) insubjects with obesity after gastric sleeve surgery and explore its correlation with lipid and glycemic parameters. Methods This retrospective cohort study included 28 obese male subjects aged 25 to 50 years, undergoing gastric sleeve surgery. Plasma levels of FGF21 were measured by enzyme-linked immunosorbent assay (ELISA) before and six to 12 months after surgery. Other parameters including body mass index (BMI), fasting glucose, lipid profile, and insulin were also assessedand homeostatic model assessment (HOMA) was used to estimate insulin resistance. Results There was a significant increase in systemic FGF21 levels after surgery (45.12 vs. 126.16 pg/mL, p = 0.007). There was also a notable reduction in BMI (51.55 vs. 39.14, p < 0.001), insulin levels (20.06 vs. 8.85 mIU/L, p < 0.001), HOMA scores (6.94 to 2.49, p < 0.001), and glucose levels (7.33 vs. 6.08, p = 0.039). Lipid profile analysis post-surgery showed an increase in total cholesterol (4.38 vs. 5.09 mmol/L, p < 0.001) and high-density lipoprotein (HDL) (0.88 vs. 1.52 mmol/L, p < 0.001), with a decrease in triglycerides (1.75 vs. 1.01 mmol/L, p = 0.007). FGF21 positively correlated with growth hormone (GH), p = 0.0015, r = 0.59, and with insulin like growth factor 1 (IGF-1), p = 0.03, r = 0.431. Conclusion FGF21 levels were increased following gastric sleeve surgery in obese male patients and were positively correlated with growth hormone and insulin IGF-1. These findings provide insights into the metabolic alterations following bariatric surgery and highlight the potential role of FGF21 as an important molecule in obesity management and treatment.

Connecting the Dots: FGF21 as a Potential Link between Obesity and Cardiovascular Health in Acute Coronary Syndrome Patients.

Fibroblast growth factor 21 (FGF21) is a hormone involved in regulating the metabolism, energy balance, and glucose homeostasis, with new studies demonstrating its beneficial effects on the heart. This study investigated the relationship between FGF21 levels and clinical, biochemical, and echocardiographic parameters in patients with acute coronary syndromes (ACSs). This study included 80 patients diagnosed with ACS between May and July 2023, categorized into four groups based on body mass index (BMI): Group 1 (BMI 18.5-24.9 kg/m2), Group 2 (BMI 25-29.9 kg/m2), Group 3 (BMI 30-34.9 kg/m2), and Group 4 (BMI ≥ 35 kg/m2). Serum FGF21 levels were measured by ELISA (Abclonal Catalog NO.: RK00084). Serum FGF21 levels were quantifiable in 55 samples (mean ± SD: 342.42 ± 430.17 pg/mL). Group-specific mean FGF21 levels were 238.98 pg/mL ± SD in Group 1 (n = 14), 296.78 pg/mL ± SD in Group 2 (n = 13), 373.77 pg/mL ± SD in Group 3 (n = 12), and 449.94 pg/mL ± SD in Group 4 (n = 16), with no statistically significant differences between groups (p = 0.47). Based on ACS diagnoses, mean FGF21 levels were 245.72 pg/mL for STEMI (n = 21), 257.89 pg/mL for NSTEMI (n = 9), and 456.28 pg/mL for unstable angina (n = 25), with no significant differences observed between these diagnostic categories. Significant correlations were identified between FGF21 levels and BMI, diastolic blood pressure, and serum chloride. Regression analyses revealed correlations with uric acid, chloride, and creatinine kinase MB. This study highlights the complex interplay between FGF21, BMI, and acute coronary syndromes. While no significant differences were found in FGF21 levels between the different BMI and ACS diagnostic groups, correlations with clinical and biochemical parameters suggest a multifaceted role of FGF21 in cardiovascular health. Further research with a larger sample size is warranted to elucidate these relationships.

Cross-sectional and Mendelian randomization study of fibroblast growth factor 19 reveals causal associations with metabolic diseases.

Fibroblast growth factor 19 (FGF19) is an intestinal-derived factor that plays a role in metabolic diseases. We performed a differential study of circulating FGF19 levels and investigated the causal effects of FGF19 on metabolic diseases using Mendelian randomization (MR). Firstly, 958 subjects were included in the physical examination center of affiliated hospital from January 2019 to January 2021. Dividing the subjects into different subgroups to compare FGF19 levels. We conducted a two-sample MR analysis of genetically predicted circulating FGF19 in relation to alcohol, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available genome-wide association study summary statistics data. The circulating FGF19 levels in nonalcoholic fatty liver disease (NAFLD) patients were lower than those without NAFLD (P<0.001). The FGF19 levels in participants with obese were lower than those without obese (P<0.001). In two-sample MR analyses, genetically predicted higher circulating FGF19 levels was significantly associated with lower aspartate aminotransferase, γ-glutamyltransferase, triglycerides, total cholesterol, low-density lipoprotein, and C-reactive protein concentrations (P<0.05) and a negative correlation with cardiovascular disease and cirrhosis whereas a positive association with type 2 diabetes mellitus (P<0.05). Our study found that circulating FGF19 levels were lower in NAFLD and obese populations. Additionally, our MR research results support the causal effects of FGF19 on improved liver function, lipids, and reduced the occurrence of inflammation, cardiovascular disease, and cirrhosis. We found a positive correlation with diabetes, which may indicate a compensatory increase in regulating above FGF19 resistance states in humans.

Effect of whey protein-derived decapeptide on mood status and blood variables in healthy adults: a randomized, double-blind, placebo-controlled cross-over trial.

The importance of maintaining good mental health with overall well-being has recently drawn attention from various fields. Functional peptides found from various protein sources reportedly reduce mental health problems. We found a new decapeptide (AJI-801) from whey proteins, which can possibly improve mood status and increase blood acetyl-L-carnitine (ALC) and fibroblast growth factor 21 (FGF21) levels. In this study, we assessed the effects of a single intake of whey protein hydrolysate containing a high amount of AJI-801 (WPH) on blood variables and mood status. A randomized, double-blind, placebo-controlled cross-over trial of two doses of WPH (100 and 500mg) was conducted. Participants, aged between 20 and 59years with fatigue were allocated to two groups based on the WPH doses received, and set first test food in each study. The blood ALC and FGF21 levels at baseline and after 60, 120, and 180min of test food intake were analyzed and the responses to the questionnaire items for mood status were obtained at baseline and after 60 and 180min of test food intake. There were no significant differences in the blood ALC and FGF21 levels between the two groups. As mood status, intake of 500-mg WPH (including 2.5-mg AJI-801) showed significant improvement in Depression/Dejection of the Profile of Mood States Questionnaire second edition and visual analog scale score for depression, as compared to the placebo. Intake of AJI-801 500-mg WPH (including 2.5-mg AJI-801) contributes to the improvement of feeling down in healthy persons with fatigue. University Hospital Medical Information Network Clinical Trial Registry (UMIN 000046829).

FGF-21 Level is higher in patients with breast cancer, a candidate for a new biomarker?

Aims: Fibroblast Growth Factor 21 (FGF-21) is a member of the FGF family involved in biological processes such as embryonic development. cell growth. morphogenesis. tissue repair. tumour growth and invasion. with mitogenic and cytogenetic activity at 19q13.33.Breast cancer is a deadly and increasing disease in women. and recent studies have shown a relationship between some cancers. including breast cancer. and hormones secreted from adipose tissue.The aim of the present study was the measurement of FGF-21 levels in patients with breast cancer and its association with breast cancer. Methods: The study included 39 patients with newly diagnosed breast cancer and 39 healthy controls. During the patients’ routine blood tests. a venous blood sample was taken and the serum levels of FGF-21 were determined by ELISA. Results: Demographic and laboratory data were compared between the newly diagnosed breast cancer group and the control group. The control group consisted of 39 participants with a mean age of 52.49 ± 7.02 years. In the patient group. 39 participants with a mean age of 52.15 ± 6.21 years were included in the study. there was no statistical difference regarding age(p&gt;0.05).In the control group. the mean FGF-21 level was 121.35 ± 88.4 pg/ml. while the mean FGF-21 level in the patient group was 171 ± 117.45 pg/ml. a statistically significant difference was detected(p value=0.036). Conclusion: FGF-21 is thought to have significant and beneficial effects on glucose. lipid and energy metabolism. as well as slowing the growth of cancer cells. and may later be used as a biological marker for breast cancer.

Heightened Serum Mitochondrial Biomarkers; FGF21 and NOS in Pediatric Anemia and a Negative Correlation between GDF15 and Serum Ferritin.

Objective: Mitochondrial dysfunction is closely linked to chronic disorders. This study aims to explore the correlation between pediatric anemia and mitochondrial markers, specifically fibroblast growth factor 21 (FGF21), growth/differentiation factor 15 (GDF-15), and nitric oxide synthase (eNOS). Method: This study included 66 children, with 34 diagnosed with anemia and 32 in the healthy control group. Statistically significant biomarkers were determined through cutoff levels. Results: Among the participants, 34 children were classified as anemic, while 32 were categorized as healthy. The study revealed that FGF21 levels ≥ 0.745 pg/mL and eNOS levels ≥ 1.265 µg/mL predicted anemia. Hemoglobin levels exhibited a negative correlation with FGF21 (r = -0.381; p = 0.002) and eNOS levels (r = -0.462; p < 0.001). Furthermore, a significant negative correlation was observed between GDF-15 and ferritin (r = -0.311; p = 0.019), while eNOS levels correlated positively with folate (r = 0.313; p = 0.019). Conclusions: Anemia induced elevated mitochondrial biomarkers; FGF21 and eNOS levels. The findings suggest that the long-term ramifications of anemia in childhood may be associated with mitochondrial dysfunction.

Fibroblast growth factor 21

Fibroblast growth factor 21 (FGF21) belongs to the FGF19 subfamily and acts systemically, playing a key role in inter-organ crosstalk. Ranging from metabolism, reproduction, and immunity, FGF21 is a pleiotropic hormone which contributes to various physiological processes. Although most of its production across species stems from hepatic tissues, expression of FGF21 in mice has also been identified in adipose tissue, thymus, heart, pancreas, and skeletal muscle. Elevated FGF21 levels are affiliated with various diseases and conditions, such as obesity, type 2 diabetes, preeclampsia, as well as cancer. Murine knockout models are viable and show modest weight gain, while overexpression and gain-of-function models display resistance to weight gain, altered bone volume, and enhanced immunity. In addition, FGF21-based therapies are at the forefront of biopharmaceutical strategies aimed at treating metabolic dysfunction-associated steatotic liver disease.

A correlation of serum fibroblast growth factor 21 level with inflammatory markers and indicators of nutritional status in patients with inflammatory bowel disease.

Fibroblast growth factor 21 (FGF21) is a stress-inducible hormone that regulates nutrient and metabolic homeostasis. Inflammatory state is one of the stimulators of FGF21 secretion. The aim of the study was to assess correlations between serum FGF21 level and inflammatory markers as well as nutritional status indicators in patients with inflammatory bowel disease (IBD). Fasting serum FGF21 level was measured using ELISA test in 105 IBD patients and 17 healthy controls. There were 31 subjects with active ulcerative colitis (UC), 16 with inactive UC, 36 with active Crohn's disease (CD), and 22 with inactive CD. Clinical and endoscopic activity of IBD was evaluated based on validated scales and indices. Fecal calprotectin, serum CRP, and selected parameters of nutritional status were tested in all patients. Serum FGF21 level was characterized by fluctuations depending on the IBD activity. FGF21 level was significantly higher in both active UC and CD compared to inactive phases of the diseases and to the controls. A correlation between FGF21 and fecal calprotectin levels was also found in UC and CD. Additionally, in CD, FGF21 level positively correlated with CRP level. In both UC and CD, a negative correlation was noted between FGF21 level and nutritional status parameters including cholesterol, protein, albumin levels, and BMI. The intensity of intestinal inflammation is related to FGF21 level, which correlates negatively with nutritional status indicators in IBD. The disturbances in FGF21 secretion may contribute to the multifactorial pathogenesis of malnutrition and weight loss in IBD patients.

The role of fibroblast growth factor 21 in metabolic processes in patients with gastrointestinal diseases

Background. Recently, the number of patients with obesity and metabolic syndrome has increased. Numerous studies to find new regulators of metabolic processes have led to the disco­very of a new fibroblast growth factor 21 (FGF21). The purpose of the study was to determine the correlation between FGF21 and meta­bolic processes among patients with gastrointestinal pathology. Materials and methods. The study was conducted in 80 patients with gastrointestinal diseases aged 18 to 66 years, the average age was (39.04 ± 1.03) years. Among the subjects, there were 56 men (70.0 %) and 24 women (30.0 %). Body composition was assessed using the Tanita MC-780MA apparatus (Japan). Serum leptin, FGF21, insulin levels were measured by enzyme-linked immunosorbent assay, and the HOMA-IR was calculated. Free fatty acids in the serum of patients were evaluated on Chromateс Crystal-5000, a gas chromatograph with a flame ionization detector. Results. The study found positive correlations between FGF21 levels and indicators of bioimpedance analysis: body mass index (r = 0.24; p = 0.004), fat mass (r = 0.26; p = 0.01) and visceral fat (r = 0.29; p = 0.01). In addition, a relationship was detected between FGF21 levels and laboratory data: insulin (r = 0.32; p = 0.001), HOMA-IR (r = 0.31; p = 0.001), leptin (r = 0.32; p = 0.001), triglyceride/high-density lipoprotein ratio (r = 0.48; p = 0.0001), and the content of certain free fatty acids. This indicates that FGF21 affects the development of obesity and metabolic disorders. It was found that FGF21 is associated with visceral obesity in patients with digestive diseases (odds ratio = 1.28, p = 0.0022). FGF21 levels above 1,317.5 pg/mL (sensitivity of 71.0 %, specificity of 53.1 %) indicate the presence of visceral obesity in patients with gastrointestinal di­seases. Conclusions. As a result of a comprehensive study, new data were obtained on the role of FGF21 as a key regulator of metabolic disorders, which is confirmed by the established relationships of this indicator with the components of lipid and carbohydrate metabolism disorders, cytokine imbalance, and hormonal activity of adipose tissue in patients with pathology of the digestive system.

Effects of aquatic versus land-based exercise on irisin and fibroblast growth factor 21 expression and triiodothyronine and free fatty acid levels in elderly women.

This study investigated the impacts of exercise on irisin and fibroblast growth factor 21 (FGF-21) expression, as well as triiodothyronine (T3 ) and free fatty acid (FFA) levels in elderly women. Thirty women aged 65 to 70 years (10 per group) were randomly assigned to aquatic exercise, land exercise, and control groups. The aquatic and land groups engaged in 3 exercise sessions per week (60 min/session) for 16 weeks. The intensity was progressively increased every 4 weeks. Irisin and FGF-21 levels significantly increased in the aquatic exercise group. In the posttest, the aquatic exercise group had the highest irisin levels. Significant findings were observed for irisin and FGF-21 for the main effect between aquatic and band exercise groups (p<0.05 for both), the main effect between measurement times (p<0.01 and p<0.001, respectively), and the interaction effect (p<0.05 and p<0.001, respectively). The irisin level was significantly higher in the aquatic than in the land group 30 minutes after the last session (p<0.05). In both exercise groups, T3 levels were significantly higher 30 minutes after the final session (p<0.05) than before the program. The FFA level was significantly higher in the aquatic exercise group than the others. In the aquatic group, FFA levels were significantly higher 30 minutes after both the first (p<0.01) and the last (p<0.001) session compared to pre-program values. Differences in exercise type and environment can promote fat metabolism by stimulating hormonal changes that induce brown fat activity and browning.

Circulating serum fibroblast growth factor 21 as risk and prognostic biomarker of retinal artery occlusion

To evaluate the predictive and prognostic value of fibroblast growth factor 21 (FGF21) levels in retinal artery occlusion (RAO) patients. In this case–control study, serum FGF21 levels were detected by using the ELISA method. Multivariable logistic regression analyses were performed to evaluate the significance of FGF21 in assessing the risk of developing RAO and its impact on vision and concurrent ischemic stroke. Compared with control group, serum FGF21 levels were significantly higher (median [IQR] = 230.90[167.40,332.20] pg/ml) in RAO patients. Multivariate logistic regression analysis showed that elevated serum FGF21 levels were associated with a higher risk of RAO occurrence (P = 0.025, OR [95%CI] = 9.672 [2.573, 36.359]) after adjustment for multiple confounding factors. Higher serum FGF21 levels were negatively associated with visual acuity improvement (P = 0.029, OR [95%CI] = 0.466[0.235, 0.925]) and positively correlated with concurrent ischemic stroke (P = 0.04, OR [95% CI] = 1.944[1.029, 3.672]) in RAO patients. Elevated serum FGF21 levels could promote the development of RAO and indicate worse visual prognosis and increase the risk of concurrent ischemic stroke, which might help clinicians early diagnose and treat RAO patients.

Organokines and liver enzymes in adolescent girls with polycystic ovary syndrome during randomized treatments.

Polycystic ovary syndrome (PCOS) is often associated with metabolic-associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function, systemic dysmetabolism, and abnormal circulating levels of signaling molecules called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage, which were assessed longitudinally in the aforementioned studies as safety markers. Liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) with those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 year. As a post hoc endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI), and meteorin-like protein (METRNL) were assessed by ELISA after 6 months of OC (N = 26) or spiomet (N = 28). Auxological, endocrine-metabolic, body composition (using DXA), and abdominal fat partitioning (using MRI) were also evaluated. Healthy, age-matched adolescent girls (N = 17) served as controls. Circulating ALT and GGT levels increased during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 months of treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls than in controls and spiomet-treated girls; and (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels were directly correlated with circulating METRNL levels only in OC-treated girls (R = 0.449, P = 0.036 and R = 0.552, P = 0.004, respectively). The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls is associated with circulating METRNL levels, suggesting enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment. https://doi.org, identifiers 10.1186/ISRCTN29234515, 10.1186/ISRCTN11062950.

Cold exposure increases circulating fibroblast growth factor 21 in the evening in males and females.

Cold exposure is linked to cardiometabolic benefits. Cold activates brown adipose tissue (BAT), increases energy expenditure, and induces secretion of the hormones fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). The cold-induced increase in energy expenditure exhibits a diurnal rhythm in men. Therefore, we aimed to investigate the effect of cold exposure on serum FGF21 and GDF15 levels in humans and whether cold-induced changes in FGF21 and GDF15 levels differ between morning and evening in males and females. In this randomized cross-over study, serum FGF21 and GDF15 levels were measured in healthy lean males (n = 12) and females (n = 12) before, during, and after 90 min of stable cold exposure in the morning (07:45 h) and evening (19:45 h) with a 1-day washout period in between. Cold exposure increased FGF21 levels in the evening compared to the morning both in males (+61% vs -13%; P < 0.001) and in females (+58% vs +8%; P < 0.001). In contrast, cold exposure did not significantly modify serum GDF15 levels, and no diurnal variation was found. Changes in FGF21 and GDF15 levels did not correlate with changes in cold-induced energy expenditure in the morning and evening. Cold exposure increased serum FGF21 levels in the evening, but not in the morning, in both males and females. GDF15 levels were not affected by cold exposure. Thus, this study suggests that the timing of cold exposure may influence cold-induced changes in FGF21 levels but not GDF15 levels and seems to be independent of changes in energy expenditure.

Regulation of Renal Cortical PPAR-alpha and Downstream Targets by Sodium Glucose Cotransporter, Type 2 Inhibition (SGLT2i) in High-Fat Fed Mice

SGLT2i has been shown to be protective of renal function and health in type 2 diabetes by unclear means. Recently we reported that empagliflozin (EMPA) treatment of mice on a high-fat diet (HFD) led to marked changes in the renal cortical lipidome, including significant upregulation of many carnitine species (11 species &gt; 35% increased, all p &lt; 0.05). Carnitines are critical in the oxidation of long-chain fatty acids by increasing their uptake into the mitochondria. The mechanism underlying this upregulation was unclear, but the peroxisome proliferator activated receptor, subtype alpha (PPARα) has been demonstrated to upregulate carnitines in other tissues. To the test the impact of EMPA (E) or control (C) treatment on renal cortical PPARα and downstream targets, male (M) and female (F) C57Bl6 mice were treated with HFD (60% by weight) ± EMPA (100 mg/kg·diet) for 12 weeks. EMPA caused a reduction in final body weight (20%) only in females. No differences were observed in final kidney weights (n = 16-18/group). Glomerular filtration rate (GFR) measured by FITC-sinistrin clearance showed a trend (p = 0.052 two-way ANOVA) for an increase by EMPA (mean ± sem, ml/min, n = 5-9): MC- 246 ± 13; ME- 291 ± 5; FC- 252 ± 13; and FE- 275 ± 36. Western blotting of cortex homogenates revealed a modest, insignificant rise in PPARα, itself with EMPA, and a higher overall abundance in females (p = 0.024 for sex, mean band density, % MC): MC-100 ± 14; ME- 108 ±11; FC- 123± 12, FE- 151± 18. Fibroblast growth factor 21 (FGF21) is a reported target of PPARα, and has been shown to be increased in liver in response to treatment with a PPARα agonist. However, FGF21 is also increased compensatorily in metabolic stress conditions, e.g., obesity. We found EMPA treatment substantially reduced circulating FGF21 levels in M, while F levels were low regardless of treatment (ng/ml): MC-3.28 ± 1.32; ME- 0.07 ± 0.027; FC- 0.19 ± 0.08, FE- 0.17 ± 0.08 (p = 0.031, 0.044, and 0.033, for treatment, sex, and interaction, respectively). FGF21 levels in liver, site of most production (measured in males only) was likewise reduced by EMPA (84%, p = 0.029, Mann-Whitney test). In contrast, no significant differences were found for renal cortical FGF21 levels. Previously, we showed PPARα whole-body knockout mice had higher renal expression of Na+K+ATPase, which was associated with higher blood pressure. Western blotting of EMPA-treated mice showed the α-1 subunit of Na+K+ATPase, a surrogate marker of proximal tubule transport activity, was significantly increased in the kidney cortex of EMPA-treated mice (band density % MC): MC-100 ± 26; ME- 145 ± 25; FC- 99 ± 22, FE- 175 ± 21 (p = 0.54, 0.016, and 0.52, for treatment, sex, and interaction, respectively). This was not associated with higher blood pressure in EMPA-treated mice, as measured by tail-cuff. Taken together, these findings do not suggest an overall increase in activity of PPARα in kidney or systemically (in liver) with EMPA. The upregulation of carnitine species in kidney may have resulted from an alternative mechanism. Additional studies are warranted to gauge the role of PPARα activation, emanating from a relatively fasted state, with SGLT2 inhibition, in the kidney and in regard to whole body metabolism. Supported by GHUCCTS (Howard and Georgetown, UL1TR001409) pilot award to CE. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Enteral Agonism of the Farnesoid X Receptor-Fibroblast Growth Factor 19 Axis Prevents Cholestasis in TPN-Fed Piglets

Total parenteral nutrition (TPN) administration provides necessary nutrients to infants who cannot tolerate enteral feedings. However, the use of TPN can result in cholestasis which can cause parenteral nutrition-associated liver diseases. Previous mitigation strategies for cholestasis have included administering bile acids enterally to encourage normal bile acid metabolism. The objective of this study was to determine if treatment of either ursodeoxycholic acid (UDCA), Tropifexor (TPX), or fibroblast growth factor 19 (FGF19) will prevent cholestasis in a piglet TPN model through the activation of the farnesoid X receptor (FXR)-FGF19 axis. We hypothesize that UDCA will have minimum effects on FXR while TPX, a potent FXR agonist, will significantly affect the FXR pathway, and FGF19 will reduce bile acid synthesis to alleviate cholestasis. Piglets received TPN for 3 weeks and were treated enterally with either UDCA (25 mg/kg*day) or TPX (7.5 μg/kg*day) with minimal milk-based formula (12 mL/kg*day), or daily intravenous FGF19 (0.25 mg/d) injection. Body weight gain was not different after 3 weeks. Plasma markers of cholestasis such as of total bile acids, bilirubin, and gamma-glutamyl transferase were lower in pigs that received TPX compared to the control treatment at the end of the study. Circulating levels of FGF19 and tissue concentrations of total bile acids were not different across treatments. In the ileum, TPX increased mRNA expression of FGF19, ileal lipid binding protein, and organic solute transporter α compared to the control pigs. All treatments reduced the mRNA expression of apical sodium-dependent bile acid transporter compared to the control treatment. TPX also increased mRNA expression of small heterodimer protein and bile salt export pump in the liver. Overall, we conclude that UDCA and FGF19 had minimal effects on cholestasis, whereas TPX prevented cholestasis in part via activation of the FXR-FGF19 axis in TPN fed piglets. NIDDK R01-DK094616 K01 DK129408 T32 NIH grant DK07664. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Expression of bile acid receptors and transporters along the intestine of patients with type 2 diabetes and controls.

The enterohepatic circulation of bile acids depends on intestinal absorption by bile acid transporters and activation of bile acid receptors, which stimulates secretion of hormones regulating glucose and lipid metabolism and appetite. Distribution of bile acid transporters and receptors in the human gut and their potential involvement in type 2 diabetes (T2D) pathophysiology remain unknown. We explored the expression of genes involved in bile acid metabolism throughout the intestines of patients with T2D and matched healthy controls. Intestinal mucosa biopsies sampled along the intestinal tract in 12 individuals with T2D and 12 healthy controls were subjected to mRNA sequencing. We report expression profiles of apical sodium-dependent bile acid transporter (ASBT), organic solute transporter (OST) α/β, farnesoid X receptor (FXR), Takeda G receptor 5 (TGR5), fibroblast growth factor 19 (FGF19) and FGF receptor 4 (FGFR4). Expression of ASBT and OSTα/β was evident in the duodenum of both groups with increasing levels through the small intestine, and no (ASBT) or decreasing levels (OSTα/β) through the large intestine. The FXR expression pattern followed that of OSTα/β whereas FGFR4 were evenly expressed through the intestines. Negligible levels of TGR5 and FGF19 were evident. Patients with T2D exhibited lower levels of FGF19, FXR, ASBT and OSTα/β mRNAs compared with healthy controls, although the differences were not statistically significant after adjusting for multiple testing. We demonstrate distinct expression patterns of bile acid transporters and receptors through the intestinal tract with signs of reduced ASBT, OSTα/β, FXR and FGF19 mRNAs in T2D.

Effects of low fat diet on inflammatory parameters in individuals with obesity/overweight and non-alcoholic fatty liver disease: A cross-sectional study.

Nonalcoholic fatty liver disease (NAFLD) is considered one of the most important causes of chronic liver disorders in the world. Dietary pattern is a modifiable risk factor that represents the main target for the prevention and treatment of NAFLD. The aim of this cross-sectional study was to assess the impact of low-fat diet on anthropometric measurements, biochemical, and inflammatory parameters in individuals with obesity/overweight and NAFLD. A total of 108 individuals (n = 59 males and n = 49 females) aged between 19 and 65 years participated in the 12-week weight loss program. Dietary treatment plans including low-fat diets were randomly prescribed for each individual. Anthropometric measurements were collected by a trained dietitian at baseline and 12-week follow-up. Blood samples were collected for each individual at baseline and 3rd month for biochemical measurements and enzyme-linked immunosorbent assay analysis for tumor necrosis factor-α (TNF-α), interleukin (IL)-6, fibroblast growth factor-21 (FGF-21), chemerin, and irisin levels in plasma. At the end of the study, body weight, body mass index, body fat % body fat mass (kg) reduced significantly in females and males (P < .05). Moreover, reductions in waist, hip, and neck circumferences were significant in both groups. Changes in alanine aminotransferase and aspartate aminotransferase levels were significant in 3rd month. After 3 months, reductions in TNF-α, IL-6, and FGF-21 levels were significant in individuals with obesity/overweight and NAFLD. While no significant change in chemerin and irisin levels was found. These results show that low-fat diet over a 12-week period led to improvements in both anthropometric measurements and biochemical parameters in individuals with obesity/overweight and NAFLD.

Supplementation of yam bean (Pachyrhizus erosus L.) fiber ameliorates dyslipidemia, liver pathology and hypersecretion of metabolic hormones in mice fed a highfat diet

Introduction: Yam bean (Pachyrhizus erosus L.) offers numerous health benefits. However, the effects of its dietary fiber (yam bean fiber, YBF) on dyslipidemia, liver disease, and the overproduction of metabolic hormones, specifically glucagon-like peptide-1 (GLP1) and fibroblast growth factor 21 (FGF21), resulting from a high-fat diet (HFD) remain underexplored. Thus, our present investigation sought to address this gap. Methods: Adult male mice (n = 24) were randomly assigned into four different groups such as normal diet (ND) as a control group, HFD, and HFD supplemented with either 2.5% or 10% YBF. After a 12-week dietary regimen, plasma lipid profiles, liver histology and biochemistry, and the levels of FGF21 and GLP-1 were assessed. Results: YBF supplementation, especially at 10% dose, effectively lowered total serum cholesterol, triglyceride (TG), and low-density lipoprotein (LDL) compared with those fed HFD (P &lt; 0.05). YBF also reduced liver weight and mitigated the elevation of malondialdehyde (MDA) and the depletion of catalase (CAT) activity induced by HFD in liver tissues (P &lt; 0.05). Furthermore, 10% YBF supplementation effectively countered liver pathology, including central vein enlargement, hepatic steatosis, inflammation, abnormal sinusoids, and hepatocyte degeneration caused by HFD (P &lt; 0.05). YBF at 10% also attenuated the HFDinduced hypersecretion of FGF21 and GLP-1 hormones. Conclusion: Our findings indicate that YBF supplementation could counteract the adverse effects of HFD, particularly in terms of dyslipidemia, liver disease, and metabolic hormone imbalances. Incorporating YBF into diets may thus offer protective benefits against HFDinduced metabolic diseases and associated health issues.

FGF21 ameliorates septic liver injury by restraining proinflammatory macrophages activation through the autophagy/HIF-1α axis

IntroductionSepsis, a systemic immune syndrome caused by severe trauma or infection, poses a substantial threat to the health of patients worldwide. The progression of sepsis is heavily influenced by septic liver injury, which is triggered by infection and cytokine storms, and has a significant impact on the tolerance and prognosis of septic patients. The objective of our study is to elucidate the biological role and molecular mechanism of fibroblast growth factor 21 (FGF21) in the process of sepsis. ObjectivesThis study was undertaken in an attempt to elucidate the function and molecular mechanism of FGF21 in therapy of sepsis. MethodsSerum concentrations of FGF21 were measured in sepsis patients and septic mice. Liver injury was compared between mice FGF21 knockout (KO) mice and wildtype (WT) mice. To assess the therapeutic potential, recombinant human FGF21 was administered to septic mice. Furthermore, the molecular mechanism of FGF21 was investigated in mice with myeloid-cell specific HIF-1α overexpression mice (LyzM-CreDIO-HIF-1α) and myeloid-cell specific Atg7 knockout mice (Atg7△mye). ResultsSerum level of FGF21 was significantly increased in sepsis patients and septic mice. Through the use of recombinant human FGF21 (rhFGF21) and FGF21 KO mice, we found that FGF21 mitigated septic liver injury by inhibiting the initiation and propagation of inflammation. Treatment with rhFGF21 effectively suppressed the activation of proinflammatory macrophages by promoting macroautophagy/autophagy degradation of hypoxia-inducible factor-1α (HIF-1α). Importantly, the therapeutic effect of rhFGF21 against septic liver injury was nullified in LyzM-CreDIO-HIF-1α mice and Atg7△mye mice. ConclusionsOur findings demonstrate that FGF21 considerably suppresses inflammation upon septic liver injury through the autophagy/ HIF-1α axis.