Several peptide growth factors, including members of the fibroblast growth factor (FGF) superfamily, are potential inducers of mesoderm in vertebrates. Receptor binding of basic FGF (FGF-2) is promoted by cell surface or extracellular matrix proteoglycans. The substantial biosynthesis of proteoglycans by embryonic cells (called embryoglycans) and their potential role as ligands for growth factor receptors led us to examine the role of embryoglycans that carry the developmentally regulated oligosaccharide epitope TEC 1, in the binding of FGF-2 to cultured rabbit inner cell masses (ICMs). Culture of isolated ICMs in the presence of FGF-2 gave rise to well delimited colonies with migrating cells at the periphery. In these cells, TEC 1 staining shifts from a punctate pattern over the entire membrane, to an apical, finely granular distribution with some internalization. This shift occurs after 96 hours in culture. Here we show that: (1) migrating cells are mesoderm-like in phenotype; (2) antibodies against TEC 1 blocked FGF-2 mediated differentiation in vitro; (3) antibodies against TEC 1 selectively blocked binding of FGF-2 to ectodermal receptors and, vice versa, the binding of TEC 1-specific antibodies to ectodermal cells can be competed by excess FGF-2; (4) the same switch in TEC 1 staining patterns was observed in vivo, between the day 7 and the day 9 rabbit embryo. These data suggest the involvement of defined species of embryonic cell surface epitopes in the regulation of FGF-2 receptor binding. Moreover, this proposed binding activity is temporally restricted to ectodermal cells and disappears early during differentiation. Thus, the apical TEC 1 redistribution can be considered as the earliest indicator of mesoderm formation.

• MeSH
• Antigenic Variation MeSH
• Blastocyst MeSH
• Antigens, Differentiation MeSH
• DNA-Binding Proteins isolation & purification   MeSH
• Ectoderm drug effects   MeSH
• Embryonic Induction * MeSH
• Epitopes MeSH
• Fetal Proteins isolation & purification   MeSH
• Fibroblast Growth Factor 2 metabolism   MeSH
• Fluorescent Antibody Technique MeSH
• Rabbits MeSH
• Mesoderm physiology   MeSH
• Oligosaccharides immunology   metabolism   MeSH
• T-Box Domain Proteins * MeSH
• Proteoglycans immunology   metabolism   MeSH
• Receptor, Fibroblast Growth Factor, Type 2 MeSH
• Receptors, Fibroblast Growth Factor metabolism   MeSH
• Receptor Protein-Tyrosine Kinases metabolism   MeSH
• Protein Binding drug effects   MeSH
• Vimentin isolation & purification   MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Brachyury Protein MeSH
• Antigens, Differentiation MeSH
• DNA-Binding Proteins MeSH
• Epitopes MeSH
• Fetal Proteins MeSH
• Fibroblast Growth Factor 2 MeSH
• Oligosaccharides MeSH
• T-Box Domain Proteins * MeSH
• Proteoglycans MeSH
• Receptor, Fibroblast Growth Factor, Type 2 MeSH
• Receptors, Fibroblast Growth Factor MeSH
• Receptor Protein-Tyrosine Kinases MeSH
• Vimentin MeSH

Basic fibroblast growth factor (FGF-2) functions as a natural inducer of mesoderm, regulator of cell differentiation and autocrine modulator of cell growth and transformation. The FGF-2 signals are transduced through receptors with intrinsic protein tyrosine kinase activity. However, receptor binding and activation is governed by extracellular matrix, cell surface or soluble proteoglycans. This paper focuses on the role of proteoglycans synthesized by embryonic cells, embryoglycans, in FGF-2 signaling via FGF receptor-1 (FGFR-1). We found that embryoglycan ectodomain Lewis X, analog of developmentally regulated embryonic cell surface epitope TEC 1, promotes oligomerization of FGF-2 in the cell free chemical crosslinking. In vitro assays show that a large molar excess of extracellular Lewis X does not inhibit binding of FGF-2 to embryonic stem (ES) cells, but prevents the mitogenic effect of FGF-2. Western blot analysis of ES cells revealed the presence of abundant 52 kDa and trace amounts of 67 and 125 kDa isoforms of FGFR-1. However, none of these isoforms undergo any detectable changes in tyrosine phosphorylation under the conditions that modulate the mitogenic effect of FGF-2. Rather, a primary substrate of all receptor tyrosine kinases, phospholipase C gamma (PLC gamma), is activated by both FGF-2 and Lewis X. The combination, FGF-2 plus Lewis X, leads to weak inhibition, when compared with the effects of FGF-2 and Lewis X, respectively. In accordance, the level of phosphorylation of non-receptor tyrosine kinase c-Src is reduced in a reversed pattern to PLC(gamma). Furthermore, in this particular cell type we show the presence of activated forms of extracellular signal-related kinase (ERK) in all nontreated and treated cells. These findings demonstrate that embryoglycan ectodomains may act as negative regulators of FGF-2-induced ES cell proliferation, most likely through the FGFR-1-independent signaling pathway.

• MeSH
• Lewis X Antigen metabolism   pharmacology   MeSH
• Cell Division drug effects   MeSH
• Cell Line MeSH
• Fibroblast Growth Factor 2 chemistry   metabolism   pharmacology   MeSH
• Phospholipase C gamma MeSH
• Type C Phospholipases metabolism   MeSH
• Phosphorylation MeSH
• Isoenzymes metabolism   MeSH
• Stem Cells cytology   drug effects   metabolism   MeSH
• Mice MeSH
• Polysaccharides metabolism   MeSH
• Proteoglycans metabolism   MeSH
• Cross-Linking Reagents MeSH
• Receptor, Fibroblast Growth Factor, Type 1 MeSH
• Receptors, Fibroblast Growth Factor metabolism   MeSH
• Signal Transduction MeSH
• src-Family Kinases metabolism   MeSH
• Receptor Protein-Tyrosine Kinases * MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Lewis X Antigen MeSH
• embryoglycan MeSH Browser
• Fgfr1 protein, mouse MeSH Browser
• Fibroblast Growth Factor 2 MeSH
• Phospholipase C gamma MeSH
• Type C Phospholipases MeSH
• Isoenzymes MeSH
• Polysaccharides MeSH
• Proteoglycans MeSH
• Cross-Linking Reagents MeSH
• Receptor, Fibroblast Growth Factor, Type 1 MeSH
• Receptors, Fibroblast Growth Factor MeSH
• src-Family Kinases MeSH
• Receptor Protein-Tyrosine Kinases * MeSH

An elevated level of fibroblast growth factor-2 (FGF-2) in peripheral blood is considered to play a role in regulating the growth of leukemia cells. Here, we show that the level of plasma FGF-2 is increased in 54% of B cell chronic lymphocytic leukemias (B-CLL) and in 44% of chronic myeloid leukemias (CML). Notably, white blood cells (WBCs) from B-CLL patients contain 18, 22 and 24 kDa isoforms of FGF-2 whereas WBCs from CML patients contain only the 24 kDa isoform. Furthermore, as cultured B-CLL WBCs release 18 kDa FGF-2 into the medium, they constitute a potential source of FGF-2 in the blood. In a receptor binding assay, 125I-FGF-2 binds weakly to B-CLL WBCs, whereas the ligand binds more strongly to CML WBCs. Correspondingly, FGF-2 is unable to activate mitogen-activated protein kinase kinase (MEK) and its substrate, extracellular signal-regulated kinase (ERK), in B-CLL cells, whereas phosphorylation of both these cell growth-related kinases increases following treatment of CML WBCs. We conclude that B-CLL WBCs secrete FGF-2 with no apparent autocrine actions. In contrast, WBCs in CML bind FGF-2 provided by other FGF-2-hyperproducing cells and activate the MEK/ERK kinase cascade, possibly to modulate cell growth.

• MeSH
• Leukemia, Lymphocytic, Chronic, B-Cell blood   MeSH
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood   MeSH
• DNA Primers MeSH
• Adult MeSH
• Fibroblast Growth Factor 2 blood   chemistry   MeSH
• Culture Media, Conditioned MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Messenger genetics   MeSH
• Molecular Weight MeSH
• Receptors, Fibroblast Growth Factor genetics   MeSH
• Base Sequence MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA Primers MeSH
• Fibroblast Growth Factor 2 MeSH
• Culture Media, Conditioned MeSH
• RNA, Messenger MeSH
• Receptors, Fibroblast Growth Factor MeSH

During development, fibroblast growth factors (FGFs) serve highly specific functions that are mediated through high-affinity transmembrane receptors and modulated by membrane-bound proteoglycans. Proteoglycans, in an embryonic environment called embryoglycans, contain numerous carbohydrate ectodomains, the structure of which undergoes rearrangement. Since they can be lost from the cell surface, they are sometimes found in extracellular space where they may also serve some regulatory function. Here we address the potential roles of three naturally occurring isoforms of Lewis X (LeX) in FGF-2-mediated proliferation of embryonic stem (ES) cells. We have found that the addition of sulfated LeX to ES cells at a concentration of 17 nM promotes FGF-2 mitogenic activity while a 10-fold higher concentration leads to a reduction of FGF-2-mediated proliferation. Notably, this dose-dependent modulation operated only for sulfated LeX. Other fucosylated motifs, basic LeX trisaccharide and sialylated LeX, also affected ES cell proliferation but the mechanism cannot be clearly correlated with the presence or absence of FGF-2. The suppression of biosynthesis of O-linked carbohydrates including LeX reduced basal proliferation of ES cells and interfered with the mitogenic effect of FGF-2. However, in inhibitor-treated cells, the stimulatory activity of FGF-2 can be reestablished to its original level by exogenous LeX oligosaccharides. Our results show that (A) O-linked LeX oligosaccharides can regulate mitogenic activity of FGF-2 in embryonic cells, (B) and this ability varies with subtle modifications in their structure. Importantly, our data represent the first insight into the mechanism of how growth factor activities might be modulated by shedded embryoglycan ectodomains.

• MeSH
• Lewis X Antigen metabolism   MeSH
• Cell Division physiology   MeSH
• Embryo, Mammalian cytology   metabolism   MeSH
• Fibroblast Growth Factor 2 metabolism   MeSH
• Immunoblotting MeSH
• Mice, Inbred Strains MeSH
• Stem Cells metabolism   MeSH
• Cells, Cultured MeSH
• Mice MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Proteoglycans biosynthesis   metabolism   MeSH
• Receptor, Fibroblast Growth Factor, Type 1 MeSH
• Receptor, Fibroblast Growth Factor, Type 2 MeSH
• Receptors, Fibroblast Growth Factor metabolism   MeSH
• Pregnancy MeSH
• Receptor Protein-Tyrosine Kinases metabolism   MeSH
• Uterus metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Lewis X Antigen MeSH
• Fgfr1 protein, mouse MeSH Browser
• Fgfr2 protein, mouse MeSH Browser
• Fibroblast Growth Factor 2 MeSH
• Proteoglycans MeSH
• Receptor, Fibroblast Growth Factor, Type 1 MeSH
• Receptor, Fibroblast Growth Factor, Type 2 MeSH
• Receptors, Fibroblast Growth Factor MeSH
• Receptor Protein-Tyrosine Kinases MeSH

Long-term delivery of growth factors and immunomodulatory agents is highly required to support the integrity of tissue in engineering constructs, e.g., formation of vasculature, and to minimize immune response in a recipient. However, for proteins with a net positive charge at the physiological pH, controlled delivery from negatively charged alginate (Alg) platforms is challenging due to electrostatic interactions that can hamper the protein release. In order to regulate such interactions between proteins and the Alg matrix, we propose to complex proteins of interest in this study - CXCL12, FGF-2, VEGF - with polyanionic heparin prior to their encapsulation into Alg microbeads of high content of α-L-guluronic acid units (high-G). This strategy effectively reduced protein interactions with Alg (as shown by model ITC and SPR experiments) and, depending on the protein type, afforded control over the protein release for at least one month. The released proteins retained their in vitro bioactivity: CXCL12 stimulated the migration of Jurkat cells, and FGF-2 and VEGF induced proliferation and maturation of HUVECs. The presence of heparin also intensified protein biological efficiency. The proposed approach for encapsulation of proteins with a positive net charge into high-G Alg hydrogels is promising for controlled long-term protein delivery under in vivo conditions.

• Keywords
• CXCL12, FGF-2, HUVECs, ITC, SPR, VEGF, alginate microbeads, bioactivity, heparin, protein release,
• MeSH
• Alginates chemistry   MeSH
• Chemokine CXCL12 chemistry   MeSH
• Human Umbilical Vein Endothelial Cells MeSH
• Fibroblast Growth Factor 2 chemistry   MeSH
• Heparin chemistry   MeSH
• Humans MeSH
• Microspheres MeSH
• Cell Line, Tumor MeSH
• Tissue Engineering MeSH
• Vascular Endothelial Growth Factor A chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH
• Names of Substances
• Alginates MeSH
• Chemokine CXCL12 MeSH
• Fibroblast Growth Factor 2 MeSH
• Heparin MeSH
• Vascular Endothelial Growth Factor A MeSH

Gastrulation is a critical step in vertebrate development, that depends on synergistic effects of several signalling molecules, including fibroblast growth factor-2 (FGF-2). To follow this phenomenon in vitro we isolated rabbit inner cell masses (ICMs) at embryonic day 4 and we exposed ICM-derived cells to FGF-2. Then, we analysed the quantitative differences in rates of protein synthesis from day 3 to day 5 of culture by two-dimensional (2D) gel electrophoresis. Here we show that both up- and down-regulation of protein synthesis took place in ICM-derived cells upon their exposure to FGF-2. The effect of FGF-2 was most pronounced at day 4 of culture, when the changes were very much in favour of a set of down-regulated proteins. To test the significance of this period of time for FGF-2-mediated regulation of protein synthesis, cells were grown without FGF-2 and then they were pulse-treated with FGF-2 at the end of day 4. When compared to the continuous culture with FGF-2, the FGF-2 pulse resulted in a quite indistinguishable pattern of up- and down-regulated proteins. Thus, the readiness of ICM-derived cells to accept and respond to the FGF-2 signals may be of limited duration.

• MeSH
• Electrophoresis, Gel, Two-Dimensional MeSH
• Time Factors MeSH
• Down-Regulation physiology   MeSH
• Fetal Proteins biosynthesis   MeSH
• Fibroblast Growth Factor 2 pharmacology   physiology   MeSH
• Rabbits embryology   MeSH
• Cells, Cultured MeSH
• Methionine metabolism   MeSH
• Up-Regulation physiology   MeSH
• Gene Expression Regulation, Developmental physiology   MeSH
• Animals MeSH
• Check Tag
• Rabbits embryology   MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Fetal Proteins MeSH
• Fibroblast Growth Factor 2 MeSH
• Methionine MeSH

The transcription program that is responsible for the pluripotency of human ESCs (hESCs) is believed to be comaintained by exogenous fibroblast growth factor-2 (FGF-2), which activates FGF receptors (FGFRs) and stimulates the mitogen-activated protein kinase (MAPK) pathway. However, the same pathway is stimulated by insulin receptors, insulin-like growth factor 1 receptors, and epidermal growth factor receptors. This mechanism is further complicated by intracrine FGF signals. Thus, the molecular mechanisms by which FGF-2 promotes the undifferentiated growth of hESCs are unclear. Here we show that, in undifferentiated hESCs, exogenous FGF-2 stimulated the expression of stem cell genes while suppressing cell death and apoptosis genes. Inhibition of autocrine FGF signaling caused upregulation of differentiation-related genes and downregulation of stem cell genes. Thus, exogenous FGF-2 reinforced the pluripotency maintenance program of intracrine FGF-2 signaling. Consistent with this hypothesis, expression of endogenous FGF-2 decreased during hESC differentiation and FGF-2 knockdown-induced hESC differentiation. In addition, FGF-2 signaling via FGFR2 activated MAPK kinase/extracellular signal-regulated kinase and AKT kinases, protected hESC from stress-induced cell death, and increased hESC adhesion and cloning efficiency. This stimulation of self-renewal, cell survival, and adhesion by exogenous and endogenous FGF-2 may synergize to maintain the undifferentiated growth of hESCs.

• MeSH
• Enzyme Activation MeSH
• Cell Adhesion drug effects   physiology   MeSH
• Cell Differentiation drug effects   physiology   MeSH
• Cell Line MeSH
• Cell Growth Processes drug effects   physiology   MeSH
• Down-Regulation MeSH
• Embryonic Stem Cells cytology   drug effects   metabolism   MeSH
• Gene Expression MeSH
• Fibroblast Growth Factor 2 genetics   metabolism   pharmacology   MeSH
• Phosphorylation MeSH
• Immunoblotting MeSH
• Humans MeSH
• Mitogen-Activated Protein Kinases metabolism   MeSH
• Oncogene Protein v-akt metabolism   MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Receptor, Fibroblast Growth Factor, Type 2 metabolism   MeSH
• Signal Transduction MeSH
• Cell Survival drug effects   physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Fibroblast Growth Factor 2 MeSH
• Mitogen-Activated Protein Kinases MeSH
• Oncogene Protein v-akt MeSH
• Receptor, Fibroblast Growth Factor, Type 2 MeSH

In a typical cell culture system, growth factors immobilized on the cell culture surfaces can serve as a reservoir of bio-signaling molecules, without the need to supplement them additionally into the culture medium. In this paper, we report on the fabrication of albumin/heparin (Alb/Hep) assemblies for controlled binding of basic fibroblast growth factor (FGF-2). The surfaces were constructed by layer-by-layer adsorption of polyelectrolytes albumin and heparin and were subsequently stabilized by covalent crosslinking with glutaraldehyde. An analysis of the surface morphology by atomic force microscopy showed that two Alb/Hep bilayers are required to cover the surface of substrate. The formation of the Alb/Hep assemblies was monitored by the surface plasmon resonance (SPR), the infrared multiinternal reflection spectroscopy (FTIR MIRS) and UV/VIS spectroscopy. The adsorption of FGF-2 on the cross-linked Alb/Hep was followed by SPR. The results revealed that FGF-2 binds to the Alb/Hep assembly in a dose and time-dependent manner up to the surface concentration of 120 ng/cm(2). The bioactivity of the adsorbed FGF-2 was assessed in experiments in vitro, using calf pulmonary arterial endothelial cells (CPAE). CPAE cells could attach and proliferate on Alb/Hep surfaces. The adsorbed FGF-2 was bioactive and stimulated both the proliferation and the differentiation of CPAE cells. The improvement was more pronounced at a lower FGF-2 surface concentration (30 ng/cm(2)) than on surfaces with a higher concentration of FGF-2 (120 ng/cm(2)).

• MeSH
• Albumins pharmacology   MeSH
• Cell Adhesion drug effects   MeSH
• Cell Differentiation drug effects   MeSH
• Cell Culture Techniques methods   MeSH
• Endothelial Cells cytology   MeSH
• Fibroblast Growth Factor 2 metabolism   pharmacology   MeSH
• Heparin pharmacology   MeSH
• Culture Media chemistry   MeSH
• Humans MeSH
• Microscopy, Atomic Force MeSH
• Cell Proliferation drug effects   MeSH
• Cattle MeSH
• Protein Binding MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Cattle MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Albumins MeSH
• Fibroblast Growth Factor 2 MeSH
• Heparin MeSH
• Culture Media MeSH

Vascular endothelial growth factor-A165 (VEGF-A165) and fibroblast growth factor-2 (FGF-2) are currently used for the functionalization of biomaterials designed for tissue engineering. We have developed a new simple method for heterologous expression and purification of VEGF-A165 and FGF-2 in the yeast expression system of Pichia pastoris. The biological activity of the growth factors was assessed in cultures of human and porcine adipose tissue-derived stem cells (ADSCs) and human umbilical vein endothelial cells (HUVECs). When added into the culture medium, VEGF-A165 stimulated proliferation only in HUVECs, while FGF-2 stimulated the proliferation of both cell types. A similar effect was achieved when the growth factors were pre-adsorbed to polystyrene wells. The effect of our recombinant growth factors was slightly lower than that of commercially available factors, which was attributed to the presence of some impurities. The stimulatory effect of the VEGF-A165 on cell adhesion was rather weak, especially in ADSCs. FGF-2 was a potent stimulator of the adhesion of ADSCs but had no to negative effect on the adhesion of HUVECs. In sum, FGF-2 and VEGF-A165 have diverse effects on the behavior of different cell types, which maybe utilized in tissue engineering.

• Keywords
• adult stem cells, basic fibroblast growth factor (bFGF), cell adhesion, cell proliferation, endothelial cells, heterologous expression, recombinant vascular endothelial growth factor (VEGF), regenerative medicine, tissue engineering, vascular replacements,
• MeSH
• Cell Adhesion drug effects   MeSH
• Human Umbilical Vein Endothelial Cells cytology   metabolism   MeSH
• Fibroblast Growth Factor 2 chemistry   genetics   pharmacology   MeSH
• Stem Cells cytology   metabolism   MeSH
• Humans MeSH
• Swine MeSH
• Cell Proliferation drug effects   MeSH
• Recombinant Proteins chemistry   pharmacology   MeSH
• Vascular Endothelial Growth Factor A chemistry   genetics   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Fibroblast Growth Factor 2 MeSH
• Recombinant Proteins MeSH
• Vascular Endothelial Growth Factor A MeSH
• VEGFA protein, human MeSH Browser

BACKGROUND: The ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients. We investigated the effect of different bariatric procedures on circulating FGF-19 levels and the resulting impact on mitochondrial health in white adipose tissue (AT). METHODS: Obese and type-2 diabetic women (n = 39, BMI > 35 kg/m2) undergoing either biliopancreatic diversion (BPD), laparoscopic greater curvature plication (LGCP), or laparoscopic adjustable gastric banding (LAGB) participated in this ethics approved study. Anthropometry, biochemical, clinical data, serum, and AT biopsies were collected before and 6 months after surgery. Mitochondrial gene expression in adipose biopsies and serum FGF-19 levels were then assessed. RESULTS: All surgeries led to metabolic improvements with BPD producing the greatest benefits on weight loss (↓30%), HbA1c (↓28%), and cholesterol (↓25%) reduction, whilst LGCP resulted in similar HbA1c improvements (adjusted for BMI). Circulating FGF-19 increased in both BPD and LGCP (χ2(2) = 8.088; P = 0.018), whilst, in LAGB, FGF-19 serum levels decreased (P = 0.028). Interestingly, circulating FGF-19 was inversely correlated with mitochondrial number in AT across all surgeries (n = 39). In contrast to LGCP and LAGB, mitochondrial number in BPD patients corresponded directly with changes in 12 of 14 mitochondrial genes assayed (P < 0.01). CONCLUSIONS: Elevated serum FGF-19 levels post-surgery were associated with improved mitochondrial health in AT and overall diabetic remission. Changes in circulating FGF-19 levels were surgery-specific, with BPD producing the best metabolic outcomes among the study procedures (BPD > LGCP > LAGB), and highlighting mitochondria in AT as a potential target of FGF-19 during diabetes remission.

• Keywords
• Bariatric surgery, FGF-19, Gut hormone, Mitochondria, Obesity, Type-2 diabetes recovery,
• MeSH
• Bariatric Surgery methods   MeSH
• Diabetes Mellitus, Type 2 metabolism   pathology   MeSH
• Adult MeSH
• Fibroblast Growth Factors metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mitochondria metabolism   MeSH
• Obesity metabolism   pathology   therapy   MeSH
• Prospective Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• FGF19 protein, human MeSH Browser
• Fibroblast Growth Factors MeSH