Fatty acid-binding proteins are a family of highly homologous cytosolic proteins, first isolated in the intestine (FABP2) and later found in liver (FABP1) and striated muscle (FABP3).
Baxa et al. (1989) purified human adipocyte FABP (called H-ALBP by them) from normal subcutaneous adipose tissue.
The 15-kD protein composed about 1% of total cytosolic protein in human adipose tissue. They also cloned a full-length
cDNA that encodes a predicted 132-amino acid polypeptide.
NCBI Summary:
FABP4 encodes the fatty acid binding protein found in adipocytes. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. It is thought that FABPs roles include fatty acid uptake, transport, and metabolism. [provided by RefSeq, Jul 2008]
General function
Intracellular signaling cascade
Comment
Free fatty acid binding protein-4 and retinol binding protein-4 in polycystic ovary syndrome: response to simvastatin and metformin therapies. Karakas SE et al. Abstract Free fatty acid binding protein-4 (FABP4) and retinol binding protein-4 (RBP4) contribute to metabolic syndrome. We investigated serum FABP4 and RBP4 responses to insulin sensitizing and lipid lowering therapies in polycystic ovary syndrome (PCOS). Sixty-two healthy, untreated women with PCOS (age 25.1???3.6 years, BMI: 24.0???4.7?kg/m(2)) were randomized to metformin (n?=?24), simvastatin (n?=?20) or metformin plus simvastatin (n?=?18) for 3 months. Anthropometric measures, fasting blood tests and oral glucose tolerance tests (OGTT) were obtained at the baseline and the end. At the baseline serum FABP4 correlated with obesity (BMI: r?=?0.63, p?
Cellular localization
Cytoplasmic
Comment
Ovarian function
Steroid metabolism
Comment
Effects of the FABP4 gene on steroid hormone secretion in goose ovarian granulosa cells. Fan R et al. (2020) 1. To investigate the physiological role of FABP4 in the goose ovary, this study determined the effects of overexpressing and siRNA interfering FABP4 on progesterone (P4) and oestradiol (E2) production in granulosa cells. Measurements were made by ELISA, real-time qRT-PCR and western blotting. 2. The concentrations of P4 and E2 in the FABP4 overexpression granulosa cells were increased compared to the control group (P>0.05 for P4; P<0.05 for E2). Likewise, the mRNA and protein expression levels of CYP11A1 and CYP19A1 were significantly higher than control group (P<0.05 or P<0.001). Conversely, the concentrations of P4 and E2 in the FABP4 silencing granulosa cells were significantly decreased compared with the control group (P<0.001). Likewise, the mRNA and protein expression levels of CYP11A1 and CYP19A1 were significantly lower than the control group (P<0.001, or P<0.01). 3. The study indicated that the FABP4 gene may regulate steroid hormone secretion and the expression of the steroidogenic genes in geese ovarian granulosa cells. These results supported the possibility that the FABP4 gene mediates ovarian steroid hormone biosynthesis function and reproduction in geese.//////////////////
Effects of the FABP4 gene on steroid hormone secretion in goose ovarian granulosa cells. Fan R et al. (2020) 1. To investigate the physiological role of FABP4 in the goose ovary, this study determined the effects of overexpressing and siRNA interfering FABP4 on progesterone (P4) and oestradiol (E2) production in granulosa cells. Measurements were made by ELISA, real-time qRT-PCR and western blotting. 2. The concentrations of P4 and E2 in the FABP4 overexpression granulosa cells were increased compared to the control group (P>0.05 for P4; P<0.05 for E2). Likewise, the mRNA and protein expression levels of CYP11A1 and CYP19A1 were significantly higher than control group (P<0.05 or P<0.001). Conversely, the concentrations of P4 and E2 in the FABP4 silencing granulosa cells were significantly decreased compared with the control group (P<0.001). Likewise, the mRNA and protein expression levels of CYP11A1 and CYP19A1 were significantly lower than the control group (P<0.001, or P<0.01). 3. The study indicated that the FABP4 gene may regulate steroid hormone secretion and the expression of the steroidogenic genes in geese ovarian granulosa cells. These results supported the possibility that the FABP4 gene mediates ovarian steroid hormone biosynthesis function and reproduction in geese.//////////////////
Chandra P. Leo, et al 2001 used
DNA array to analyze changes in preovulatory gene expression in the rat
Ovary. They reported that
the
screening identified a group of candidate genes whose ovarian
expression and gonadotropin regulation was hitherto unknown. The
induction of three of these genes, encoding cutaneous fatty acid-binding
protein, the interleukin-4 receptor alpha chain, and prepronociceptin, was
confirmed and further characterized by Northern blot analysis. In addition,
in situ hybridization analysis showed that hCG administration resulted in
exclusive or predominant expression of all three genes in theca cells.
By contrast, the message for heart FABP was the most highly repressed message
among the 597 genes represented in the array.
Three other genes for FABPs-intestinal FABP, adipocyte FABP, and liver
FABP-were also represented on the array, but the quantification revealed no clear regulation of
the mRNA by hCG.
Expression regulated by
Steroids, Growth Factors/ cytokines
Comment
Expression and regulation of adipocyte fatty acid binding protein in granulosa cells and its relation with clinical characteristics of polycystic ovary syndrome. Hu W et al. Increased expression of adipocyte fatty acid binding protein (FABP4) is associated with type 2 diabetic, high triglycerides, increased lipid peroxidation, and inflammation markers. To study the expression of FABP4 mRNA in granulosa cells of patients with polycystic ovary syndrome (PCOS) and the impact of testosterone, insulin, and PPAR? agonist rosiglitazone on granulosa cells (GCs), and to investigate the relationship of serum FABP4 levels with clinical characteristics in patients with PCOS. The expression of FABP4 mRNA in GCs of patients with PCOS and normal controls were assayed by RT-PCR. We assessed the level of FABP4 mRNA after treatment with testosterone, insulin, and rosiglitazone in GCs from normal controls. Serum FABP4 were assayed from 96 patients with PCOS (obese and nonobese 48 cases, respectively) and 80 healthy normal controls (obese and the nonobese 40 cases, respectively). The expression of FABP4 mRNA was higher in the GCs of PCOS than that of the controls (P ?
Ovarian localization
Granulosa, Ovarian tumor
Comment
Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nieman KM et al. Intra-abdominal tumors, such as ovarian cancer, have a clear predilection for metastasis to the omentum, an organ primarily composed of adipocytes. Currently, it is unclear why tumor cells preferentially home to and proliferate in the omentum, yet omental metastases typically represent the largest tumor in the abdominal cavities of women with ovarian cancer. We show here that primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells, and that adipokines including interleukin-8 (IL-8) mediate these activities. Adipocyte-ovarian cancer cell coculture led to the direct transfer of lipids from adipocytes to ovarian cancer cells and promoted in vitro and in vivo tumor growth. Furthermore, coculture induced lipolysis in adipocytes and ?oxidation in cancer cells, suggesting adipocytes act as an energy source for the cancer cells. A protein array identified upregulation of fatty acid-binding protein 4 (FABP4, also known as aP2) in omental metastases as compared to primary ovarian tumors, and FABP4 expression was detected in ovarian cancer cells at the adipocyte-tumor cell interface. FABP4 deficiency substantially impaired metastatic tumor growth in mice, indicating that FABP4 has a key role in ovarian cancer metastasis. These data indicate adipocytes provide fatty acids for rapid tumor growth, identifying lipid metabolism and transport as new targets for the treatment of cancers where adipocytes are a major component of the microenvironment.
Occurrence of immunoreactivity for adipocyte-type fatty acid binding protein in degenerating granulosa cells in atretic antral follicles of mouse ovary. Nourani MR et al. The localization of adipocyte-type fatty acid binding protein (A-FABP) in the mature mouse ovary was examined by immuno-light and electron microscopy. Solitary round cells showing the distinct immunoreactivity for A-FABP were detected in 1-6 antral follicles. In sets of two consecutive sections in a mirror alignment on slide glasses which were treated for immunoreactivity for A-FABP and TUNEL reaction separately, cells immunoreactive for A-FABP appeared in the same antral follicles as containing cells exhibiting TUNEL-reaction. In immunoelectron microscopy, A-FABP-immunopositive cells were found to contain highly electron-dense nuclei of round, irregular or crescent shapes together with cytoplasmic remnants without any features of macrophages or cells of extrinsic origin. Therefore the cells were identified as apoptotic granulosa cells. The apoptotic cells immunoreactive for A-FABP were often seen to be enclosed/engulfed in adjacent cells exhibiting normal ultrastructures without containing numerous lysosomes. The present findings suggest that A-FABP is involved in the apoptosis of ovarian granulosa cells, probably through its interaction with peroxisome proliferator activated receptors.
Follicle stages
Preovulatory
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Hotamisligil et al. (1996) noted that fatty acid-binding proteins are small cytoplasmic proteins that are expressed in a
highly tissue-specific manner. They investigated the function of adipocyte fatty acid-binding proteins by creating a null
mutation in the murine aP2 gene by homologous recombination. The aP2-deficient mice were developmentally and
metabolically normal.
Species: human
Mutation name: None
type: naturally occurring fertility: subfertile Comment: FABP4: a novel candidate gene for polycystic ovary syndrome. Wang J et al. BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder involving a number of genetic and environmental factors. Adipocyte-fatty acid-binding protein (FABP4) is an adipokine regulating systemic insulin sensitivity, lipid and glucose metabolism. In humans serum FABP4 levels correlate significantly with features of PCOS. Previous researches showed strong evidences that FABP4 impacted the developing of PCOS possibly through its protein alteration or transcription regulation. Thus, the present study is the first attempt to identify the possible genetic role of FABP4 gene in the development of PCOS. METHODS: About 1000 bp of the promoter region and four exons of FABP4 gene of 178 PCOS patients and 171 healthy controls were directly sequenced. RESULTS: Three polymorphisms, rs16909225, rs3834363, and rs16909220, were identified, of which rs16909225 and rs16909220 were completely linked (r (2) = 1) and not associated with the development of PCOS, while the -2-bp/-2-bp genotype of rs3834363 was significantly higher in PCOS than in the controls (chi(2) = 7.39, df = 1, P = 0.007, OR = 1.80 95% CI: 1.18-2.75). CONCLUSION: The present study is the first to establish an association between FABP4 gene polymorphisms and the development of PCOS.