Adipocyte Fatty Acid-binding Protein Research Articles

Dysregulation of adipokines levels among healthy first-degree relatives of type 2 diabetes patients

BackgroundLeptin, adiponectin and its ratio (L/A), as well as adipocyte fatty acid binding protein (A-FABP) have shown association to type 2 diabetes and atherosclerosis. Since first degree relatives (FDR) of type 2 diabetes are known to have higher risks of developing aforementioned diseases, this study aimed to see differences in adipokines profiles between FDR of type 2 diabetes and non-FDR counterpart. MethodsAge, sex and body mass index (BMI)-matched normotensive-normoglycemic subjects, aged 19–39 years with BMI<30 kg/m2, were included in this cross-sectional study. Serum adiponectin, leptin, and A-FABP levels were measured by sandwich ELISA while HOMA-IR was calculated from fasting blood glucose and insulin levels. ResultsOf 116 subjects recruited, there were significant difference of insulin level (6.00 vs 5.00 μIU/mL, P = 0.029) and HOMA-IR (1.27 vs 1.10, P = 0.028). Adiponectin, leptin, L/A ratio, and A-FABP levels were not statistically different between FDR and non-FDR groups. Stratified by BMI, non-obese FDR had higher L/A ratio (0.83 vs 0.49, P = 0.020) compared to those of corresponding non-FDR. In multivariate analysis, after adjusting for age, sex, waist circumference, BMI, and metabolic profiles (HbA1C, HOMA-IR, LDL-C, HDL-C, and triglyceride levels), FDR status became significantly associated with adiponectin level, and in non-obese subgroup, remained its significance with L/A ratio. ConclusionThe FDR status was independently associated with adiponectin level. Furthermore, higher L/A ratio was more pronounced in non-obese FDR than those of non-FDR subjects, suggesting that FDR status may already contribute to the development of adipokines dysregulation before obesity occurs.

Study on the Association Between Dietary Quality and Overweight/Obesity of Han Nationality with Cold in Yunnan Plateau by DBI-16 - A Study Based on a Multi-Ethnic Cohort in China.

In recent years, with the rapidly development of economic globalization, residents' dietary structure has undergone major changes, and diet have emerged as an important environmental factors linked to the increased incidence of obesity. Therefore, evaluating the overall dietary quality and structure of residents, further clarifying the main dietary factors that lead to disease occurrence, is of great practical significance for disease prevention and control. Baseline data from the China Multi-Ethnic Cohort study (CMEC), Han people living in high-altitude and cold regions of Yunnan Province, which was 1518 participants. In this study, the dietary balance index (DBI-16) was used (i) To evaluate the dietary quality of Han nationality residents 30-79 years old in the Yunnan plateau; (ii) To analyze the correlation between the dietary quality and overweight/obesity; (iii) And to provide reference basis of nutritional intervention for local residents and explore the main dietary factors affecting their health status. The dietary structure of the Han nationality residents in the cold regions of Yunnan plateau is unreasonable. Firstly, the intake of cereals, fruits, dairy, eggs and fishes is insufficient to varying degrees, while the intake of beans, poultry, and cooking oil is relatively high. Secondly, the dietary patterns of normal groups, the overweight and obese groups obeyed the A, E, H and I dietary patterns, and the serum Leptin and adipocyte fatty acid binding protein (A-FABP) levels of the overweight and obese group were higher than the normal group between the different dietary patterns (P < 0.05, r > 0). Additionally, excessive dietary intake was positively correlated with a higher serum UCP1 level (P < 0.05, r > 0). In comparison, insufficient dietary intake was positively correlated with a higher serum A-FABP level (P < 0.05, r > 0). Through the DBI-16, it is found that the dietary structure of the Han nationality residents in the cold regions of Yunnan plateau was in a serious imbalance state, and nutritional guidance and intervention should be further strengthened.

Elevated Serum Concentration of Adipocyte Fatty Acid-Binding Protein Correlates with the Markers of Abdominal Obesity Independently of Thyroid Hormones in Non-Obese Women with Polycystic Ovary Syndrome.

Adipocyte fatty acid-binding protein (A-FABP) is mainly expressed in adipocytes. The risk of abdominal obesity and autoimmune thyroid disease is increased in women with polycystic ovary syndrome (PCOS). The objective of this study was to explore the relationship of serum concentration of A-FABP with parameters of obesity, e.g., waist to hip ratio (WHR) and the amount of adipose tissue assessed by bioelectrical impedance analysis (BIA), and thyroid hormone homeostasis in women with PCOS. We examined 66 women with PCOS and 67 healthy women. Serum concentrations of A-FABP and thyroid hormones were measured; the FT3/FT4 ratio, thyroid-stimulating hormone index (TSHI), thyrotrope thyroxine resistance index (TT4RI) and thyroid feedback quantile-based index (TFQI) were calculated. In the PCOS group, serum concentrations of A-FABP, FT3 and the FT3/FT4 ratio were significantly higher in comparison to the control group (all p < 0.05). A correlation of A-FABP with WHR (r = 0.26, p = 0.04) and the percentage of adipose tissue (r = 0.33, p = 0.01) has been found only in women with PCOS. We observed no correlation between serum levels of A-FABP and TSHI, TT4RI or TFQI in women with PCOS (all p > 0.05). Our results indicate that A-FABP is an adipokine that may be connected with abdominal obesity independently of thyroid hormone homeostasis in PCOS patients.

1411-P: Serum Adipocyte Fatty Acid–Binding Protein Is Related to the Development of Prediabetes—Tokushima Cohort Study

Adipocyte fatty acid-binding protein (A-FABP/FABP4) is abundantly expressed in mature adipocytes and presumably secreted into the plasma from these cells. Emerging evidence suggests that FABP4 may be involved in the development of insulin resistance. However, prospective cohort studies to prove their causative relationship are still limited. The aim of the present study was to investigate the association between serum concentration of FABP4 and incidence of prediabetes. Here we analyzed data of a prospective cohort study, which was conducted during 2008-2019 in Japan. A total of 527 subjects without prediabetes aged 20 to 60 years were followed up prospectively. Prediabetes was defined as either: 1) fasting plasma glucose ≥ 100 mg/dl, 2) HbA1c ≥ 5.7% or 3) medication for hyperglycemia. The subjects were divided into three categories based on the tertiles of baseline serum FABP4 for each sex (male: &amp;lt; 7.8, 7.8-11.3 and &amp;gt; 11.3 ng/ml, female: &amp;lt;10.0, 10.0-13.0 and &amp;gt; 13.0 ng/ml). The age- and sex-adjusted incidence of prediabetes significantly increased with increasing tertile of serum FABP4 level at baseline (P for trend&amp;lt;0.001). In multivariate analysis after adjusting for age, sex, BMI, smoking habit, alcohol intake, regular exercise, HDL cholesterol, triglycerides, family history of diabetes, and hypertension, the hazard ratio of prediabetes was 1.65 [95% confidence interval:1.09 to 2.50, P=0.02] in the highest tertile of baseline serum FABP4, when compared with the lowest tertile. In addition, serum FABP4 at baseline was significantly higher in the subjects who developed diabetes, rather than prediabetes, during the follow-up period. Our findings suggest that increased serum concentration of FABP4 is an independent predictor of the incidence of prediabetes in Japanese and is related to the severity of future glucose intolerance. These results imply that altered FABP4 may associate with disorders of glucose metabolism from the early stages. Disclosure A.Hata: None. N.Aki: None. T.Ichihara: None. T.Minagawa: None. A.Tamura: None. Y.Kuwamura: None. M.Funaki: Board Member; Mechanogenic, Inc. Funding Grants-in-Aid for Scientific Research (to M.F.); Japan Society for the Promotion of Science (25860439 to A.H.)

1610-P: Fatty Acid–Binding Protein 4 as a Biomarker for Remission of Type 2 Diabetes

Elevated levels of circulating Fatty Acid Binding Protein 4 (FABP4), also named adipocyte FABP (A-FABP), are associated with obesity, diabetes mellitus, insulin resistance, hypertension, and cardiovascular risk. FABP4 is a protein found in high levels in both macrophages and adipocytes. Release of FABP4 from adipocytes via lipolysis, and release from macrophages during inflammation, plays a key role in development of insulin resistance and diabetes mellitus. We studied the effect of a high protein (HP; 30% protein, 40% carbohydrate, 30% fat) diet vs high carbohydrate (HC;15% protein, 55% carbohydrate, 30% fat) diet in patients recently diagnosed with Type 2 Diabetes (T2D). We determined the levels of circulating FABP4 and metabolic parameters in the HP vs HC groups at baseline and 6 months after consuming the respective diets. Participants (14) were randomized to a HP or HC diet for 6 months. All food was provided and designed for weight loss. After 6 months on the HP diet, 100% of the subjects had remission of T2D to Normal Glucose Tolerance (NGT), whereas only 16.6% of subjects on HC diet had remission of T2D. The HP diet group exhibited significant improvement in a) insulin sensitivity (p=0.001), b) inflammatory cytokines (p=0.001), C) cardiovascular risk factors (p=0.004) compared to the HC diet group at 6 months. Although weight loss in both groups was around 10% at 6 months, the HP group lost % fat mass, whereas, the HC group lost both % muscle and fat mass. Average level of FABP4 decrease after 6 months was 12,831 pg/ml in the 8 participants on the HP diet, compared to only a 1183 pg/ml average decrease after 6 months for the 6 HC participants. Conclusions: These data showed a significant decrease of circulating FABP4 in the HP but not HC diet group and suggests that a high protein diet could be an optimal way to reduce FABP4 levels in the blood. This could subsequently lower the risk of development/progression of insulin resistance, T2D, inflammation and cardiovascular risk conditions and serve as a biomarker. Disclosure F.B.Stentz: None. Funding AD Baskin

The Interplay of Adipokines, Body Composition and Glucose Homeostasis in Pregnant Women with a History of RYGB Operation.

Roux-en-Y gastric bypass operations (RYGB-OP) and pregnancy alter glucose homeostasis and the adipokine profile. This study investigates the relationship between adipokines and glucose metabolism during pregnancy post-RYGB-OP. (1) Methods: This is a post hoc analysis of a prospective cohort study during pregnancy in 25 women with an RYGB-OP (RY), 19 women with obesity (OB), and 19 normal-weight (NW) controls. Bioimpedance analysis (BIA) was used for metabolic characterization. Plasma levels of adiponectin, leptin, fibroblast-growth-factor 21 (FGF21), adipocyte fatty acid binding protein (AFABP), afamin, and secretagogin were obtained. (2) Results: The phase angle (φ) was lower in RY compared to OB and NW. Compared to OB, RY, and NW had lower leptin and AFABP levels, and higher adiponectin levels. φ correlated positively with leptin in RY (R = 0.63, p < 0.05) and negatively with adiponectin in OB and NW (R = -0.69, R = -0.69, p < 0.05). In RY, the Matsuda index correlated positively with FGF21 (R = 0.55, p < 0.05) and negatively with leptin (R = -0.5, p < 0.05). In OB, FGF21 correlated negatively with the disposition index (R = -0.66, p < 0.05). (3) Conclusions: The leptin, adiponectin, and AFABP levels differ between RY, OB, and NW and correlate with glucose metabolism and body composition. Thus, adipokines might influence energy homeostasis and maintenance of cellular health during pregnancy.

36 Productive and Physiological Responses of Feedlot Cattle Receiving Different Sources of Ca Salts of Fatty Acids in the Finishing Diet

Abstract This experiment compared productive and physiological responses in feedlot cattle receiving a finishing diet that included Ca salts of palm oil (CSPALM), or a blend of Ca salts of palm, cottonseed, and soybean oils (CSMIX). Ninety yearling steers were housed in 15 pens equipped with Calan-gate feeders (6 steers/pen). Steers within each pen were ranked by shrunk body weight (BW; 410 ± 3.3 kg) on d 0 and assigned to receive a total-mixed ration (TMR) containing (as-fed basis) 2% of CSMIX (n = 30), 2% of CSPALM (n = 30), or no supplemental fat (CON; n = 30). Individual TMR intake was evaluated weekly. Blood samples were collected on d 0, 28, 56, 119, and 147. Samples of the Longissimus muscle (LM) were collected on d 84 via needle biopsy. Upon slaughter on d 148, hot carcass weight (HCW) was recorded and used to determine final BW (63% dressing), whereas one LM steak sample (2.54 cm) was removed from the right side of each carcass. Steer ADG was greater (P = 0.02) for CSMIX compared with CSPALM and tended to be greater (P = 0.09) for CSMIX compared with CON. Feed efficiency was greater (P ≤ 0.05) for CSMIX compared with CSPALM and CON, and carcass LM area was less (P = 0.01) for CSPALM compared with CSMIX and CON. No treatment effects were detected (P ≥ 0.21) for TMR intake, final BW, and other carcass merit traits including marbling. Mean plasma cholesterol concentrations were greater (P &amp;lt; 0.01) in CSMIX and CSPALM compared with CON, and expression of adipocyte fatty acid binding protein in the LM was greater (P ≤ 0.04) in CSPALM compared with CSMIX and CON. No treatment effects were detected (P ≥ 0.15) for plasma concentrations of glucose, insulin, insulin-like growth factor I, and leptin, nor for other LM genes associated with marbling and muscle growth. Concentrations of total fatty acids (FA) in plasma and in LM steaks were greater (P &amp;lt; 0.01) in CSMIX compared with CSPALM and CON, and greater (P &amp;lt; 0.01) in the LM steaks of CSPALM steers compared with CON. Moreover, steers receiving CSMIX had greater (P &amp;lt; 0.01) concentrations of polyunsaturated and ω-6 FA in plasma samples and LM steaks compared with CSPALM and CON. Collectively, supplementing CSMIX improved performance traits and FA profile in the LM of feedlot steers, but the same responses were not observed when CSPALM was offered. The advantages noted from CSMIX supplementation appear to be resultant from the nutraceutical benefits of increased polyunsaturated ω-6 FA supply to the finishing diet.

Adipocyte "Fatty Acid Binding Protein" Gene Polymorphisms (rs1054135, rs16909196 and rs16909187) in Jordanians with Obesity and Type 2 Diabetes Mellitus.

Obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia may result from the interactions of genetic and environmental factors. There are controversial reports concerning the association of polymorphisms (rs1054135, rs16909196 and rs16909187) in the gene of adipocyte fatty acid binding protein (FABP4) with obesity and T2DM. Therefore, we designed this study to determine the association of these polymorphisms with obesity, T2DM, and dyslipidemia among Jordanian subjects. The study was approved by the National Center for Diabetes, Endocrinology, and Genetics (NCDEG) Institutional Review Board (IRB). A total of 397 subjects were enrolled in the study and divided into four groups as described in materials and methods section. The fatty acid binding protein 4 (FABP4) gene containing (rs1054135, rs16909196 and rs16909187) single nucleotide polymorphisms (SNP) was amplified by polymerase chain reaction (PCR) followed by Sanger DNA sequencing of the PCR product. None of the three SNPs were associated with T2DM (p > 0.05). The rs16909187 and rs16909196 were significantly associated with obesity. The wild type (CC) of rs16909187 was significantly higher among the overweight and obese group compared with normal weight controls (OD = 2.17, 95% CI = 1.18 - 3.96, p =0.01). The wild type of rs16909196 (AA) was significantly higher among the overweight and obese group compared to controls, (OD = 2.26, 95% CI = 1.24 - 4.14, p = 0.01). These results may indicate that the wild-type may be a risk factor for obesity.Only the rs1054135 SNP was significantly associated with increased low density lipoprotein (LDL) levels in the overweight and obese group compared with the controls (p = 0.03). The wild-type genotypes of rs16909196 and rs16909187 may be risk factors for obesity but not T2DM. None of the three SNPs was associated with T2DM.

Leuconostoc Citreum Inhibits Adipogenesis and Lipogenesis by Inhibiting p38 MAPK/Erk 44/42 and Stimulating AMPKα Signaling Pathways.

Probiotics provide a range of health benefits. Several studies have shown that using probiotics in obesity treatment can reduce bodyweight. However, such treatments are still restricted. Leuconostoc citreum, an epiphytic bacterium, is widely used in a variety of biological applications. However, few studies have investigated the role of Leuconostoc spp. in adipocyte differentiation and its molecular mechanisms. Therefore, the objective of this study was to determine the effects of cell-free metabolites of L. citreum (LSC) on adipogenesis, lipogenesis, and lipolysis in 3T3-L1 adipocytes. The results showed that LSC treatment reduced the accumulation of lipid droplets and expression levels of CCAAT/ enhancer-binding protein-α & β (C/EBP-α & β), peroxisome proliferator-activated receptor-γ (PPAR-γ), serum regulatory binding protein-1c (SREBP-1c), adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), resistin, pp38MAPK, and pErk 44/42. However, compared to control cells, adiponectin, an insulin sensitizer, was elevated in adipocytes treated with LSC. In addition, LSC treatment increased lipolysis by increasing pAMPK-α and suppressing FAS, ACC, and PPAR-γ expression, similarly to the effects of AICAR, an AMPK agonist. In conclusion, L. citreum is a novel probiotic strain that can be used to treat obesity and its associated metabolic disorders.

Functional Characterization of Transgenic Mice Overexpressing Human 15-Lipoxygenase-1 (ALOX15) under the Control of the aP2 Promoter.

Arachidonic acid lipoxygenases (ALOX) have been implicated in the pathogenesis of inflammatory, hyperproliferative, neurodegenerative, and metabolic diseases, but the physiological function of ALOX15 still remains a matter of discussion. To contribute to this discussion, we created transgenic mice (aP2-ALOX15 mice) expressing human ALOX15 under the control of the aP2 (adipocyte fatty acid binding protein 2) promoter, which directs expression of the transgene to mesenchymal cells. Fluorescence in situ hybridization and whole-genome sequencing indicated transgene insertion into the E1-2 region of chromosome 2. The transgene was highly expressed in adipocytes, bone marrow cells, and peritoneal macrophages, and ex vivo activity assays proved the catalytic activity of the transgenic enzyme. LC-MS/MS-based plasma oxylipidome analyses of the aP2-ALOX15 mice suggested in vivo activity of the transgenic enzyme. The aP2-ALOX15 mice were viable, could reproduce normally, and did not show major phenotypic alterations when compared with wildtype control animals. However, they exhibited gender-specific differences with wildtype controls when their body-weight kinetics were evaluated during adolescence and early adulthood. The aP2-ALOX15 mice characterized here can now be used for gain-of-function studies evaluating the biological role of ALOX15 in adipose tissue and hematopoietic cells.

Circulating AFABP, FGF21, and PEDF Levels as Prognostic Biomarkers of Sight-threatening Diabetic Retinopathy.

Adipocyte fatty acid-binding protein (AFABP), fibroblast growth factor 21 (FGF21), and pigment epithelium-derived factor (PEDF) are 3 diabetes-related biomarkers whose circulating levels had been shown to associate with nephropathy progression in Chinese patients with type 2 diabetes. Here, we evaluated and compared their prospective associations with the development of sight-threatening DR (STDR), another important diabetic microvascular complication. Baseline serum AFABP, PEDF, and FGF21 levels were measured in 4760 Chinese individuals with type 2 diabetes and without STDR at baseline. The associations of these biomarkers with incident STDR were analyzed using Cox regression analysis. Among these 4760 participants (mean diabetes duration of 11 years and ≥ 50% with nonproliferative DR at baseline), 172 participants developed STDR over a median follow-up of 8.8 years. Participants with incident STDR had comparable baseline serum FGF21 levels but significantly higher baseline serum AFABP and PEDF levels (both P < .001) than those without. However, in multivariable Cox regression analysis, only serum AFABP remained independently associated with incident STDR (hazard ratio 1.28; 95% CI, 1.05-1.55; P = .013). The addition of serum AFABP to a clinical model of conventional STDR risk factors including diabetes duration, glycemic control, albuminuria, and baseline DR status significantly improved the c statistics (P < .001), net reclassification index (P = .0027), and integrated discrimination index (P = .033) in predicting incident STDR among participants without DR or with mild DR at baseline. Among the 3 diabetes-related biomarkers, serum AFABP level appeared to be a more clinically useful biomarker for predicting incident STDR in type 2 diabetes.

The Association and Joint Effect of Adipocyte Fatty Acid Binding Protein and Obesity Phenotype With Cardiovascular Events.

There is little evidence regarding the joint effect of serum adipocyte fatty acid binding protein (A-FABP) levels and obesity phenotype on the risk of cardiovascular events. To explore the association between serum A-FABP levels and obesity phenotype defined by fat percentage (fat%) and visceral fat area (VFA), and their joint impact on incident cardiovascular events. A total of 1345 residents (579 men and 766 women) without previous cardiovascular diseases at baseline, with body composition and serum A-FABP data available, were included. A bioelectrical impedance analyzer and magnetic resonance imaging were used to assess fat% and VFA, respectively. During a mean follow-up of 7.6 years, 136 cases of cardiovascular events (13.9 per 1000 person-years) occurred. Per 1-unit increase in loge-transformed A-FABP levels was associated with an increase in cardiovascular events risk (hazard ratio [HR] 1.87, 95% CI 1.33-2.63). The highest tertiles of fat% and VFA levels were related to higher risks of cardiovascular events (fat%: HR 2.38, 95% CI 1.49-3.81; VFA: HR 1.79, 95% CI 1.09-2.93). The association between A-FABP levels and cardiovascular events was more pronounced in participants with low fat%, regardless of VFA levels. The joint effect of high A-FABP levels and obesity resulted in a greater risk of cardiovascular events. Serum A-FABP levels were significantly associated with the risk of cardiovascular events, and this pattern of association was more prominent among the population with low fat%, which was independent of VFA.

Correlation between adipocyte fatty acid binding protein 4 with albuminuria in patients with diabetic nephropathy

Correlation between adipocyte fatty acid binding protein 4 with albuminuria in patients with diabetic nephropathy

Productive and physiological responses of feedlot cattle receiving different sources of Ca salts of fatty acids in the finishing diet.

This study evaluated productive and physiological responses in feedlot cattle receiving a finishing diet that included Ca salts of palm oil (CSPALM), or a blend of Ca salts of palm, cottonseed, and soybean oils (CSMIX). Ninety yearling steers were housed in 15 pens equipped with Calan-gate feeders (6 steers/pen). Steers within each pen were stratified by shrunk body weight (BW; 410 ± 3.3 kg across pens) on d 0 and assigned to receive a total-mixed ration (TMR) containing (dry matter basis) 2.2% of CSPALM (n = 30), 2.2% of CSMIX (n = 30), or no supplemental fat (CON; n = 30). Individual TMR intake was evaluated weekly. Blood samples were collected on d 0, 28, 56, 91, 119, and 147. Samples of the Longissimus muscle (LM) were collected on d 84 via biopsy. Upon slaughter on d 148, hot carcass weight (HCW) was recorded to estimate final BW (63% dressing), and one LM steak sample (2.54 cm thickness) was removed from the right side of each carcass. Steer ADG was greater (P = 0.02) for CSMIX compared with CSPALM and tended to be greater (P = 0.09) for CSMIX compared with CON. The gain:feed ratio was greater (P ≤ 0.05) for CSMIX compared with CSPALM and CON, and carcass LM area was less (P = 0.01) for CSPALM compared with CSMIX and CON. No treatment effects were detected (P ≥ 0.21) for TMR intake, final BW, and other carcass merit traits including marbling. Mean plasma cholesterol concentrations were greater (P < 0.01) in CSMIX and CSPALM compared with CON, and mRNA expression of adipocyte fatty acid binding protein in the LM on d 84 was greater (P ≤ 0.04) in CSPALM compared with CSMIX and CON. No treatment effects were detected (P ≥ 0.15) for plasma concentrations of glucose, insulin, insulin-like growth factor I, and leptin, nor for other LM genes associated with marbling and muscle growth. Concentrations of total fatty acids (FA) in plasma and LM steak samples were greater (P < 0.01) in CSMIX compared with CSPALM and CON, and greater (P < 0.01) in the LM samples of CSPALM compared with CON. Steers receiving CSMIX had greater (P < 0.01) concentrations of polyunsaturated and ω-6 FA in plasma and LM steak samples compared with CSPALM and CON. Supplementing CSMIX improved gain efficiency and FA profile in the LM of feedlot steers compared with the CON diet, but the same responses were not observed when CSPALM was offered. Perhaps the advantages from CSMIX supplementation resulted from increasing the supply of polyunsaturated and ω-6 FA to the finishing diet.

Methionine sulfoxide suppresses adipogenic differentiation by regulating the mitogen-activated protein kinase signaling pathway.

In this study, methionine sulfoxide (MetO) was identified as an active metabolite that suppresses adipogenesis after screening obese individuals versus the normal population. MetO suppressed the gene and protein expression of CCAAT/enhancer binding protein (C/EBP) α, adipocyte fatty acid binding protein 4 (FABP4), and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) during human preadipocyte (HPA) differentiation. Adipogenesis decreased following MetO treatment; however, the preadipocyte number, proliferation, and apoptosis were unaffected. The activity of phosphorylated extracellular signal-related kinase (P-ERK) of the mitogen-activated protein kinase (MAPK) pathway was significantly inhibited in HPA after MetO treatment. Furthermore, treatment of preadipocytes with the selective P-ERK1/2 agonist Ro 67-7476 abolished the effect of MetO against adipogenesis suggesting that MetO function is dependent on the MAPK pathway. The mechanistic insights of adipogenesis suppression by MetO presented in this study shows its potential as an antiobesity drug.

Conjugated linoleic acid regulates adipocyte fatty acid binding protein expression via peroxisome proliferator-activated receptor α signaling pathway and increases intramuscular fat content.

Intramuscular fat (IMF) is correlated positively with meat tenderness, juiciness and taste that affected sensory meat quality. Conjugated linoleic acid (CLA) has been extensively researched to increase IMF content in animals, however, the regulatory mechanism remains unclear. Adipocyte fatty acid binding protein (A-FABP) gene has been proposed as candidates for IMF accretion. The purpose of this study is to explore the molecular regulatory pathways of CLA on intramuscular fat deposition. Here, our results by cell lines indicated that CLA treatment promoted the expression of A-FABP through activated the transcription factor of peroxisome proliferator-activated receptor α (PPARα). Moreover, in an animal model, we discovered that dietary supplemental with CLA significantly enhanced IMF deposition by up-regulating the mRNA and protein expression of PPARα and A-FABP in the muscle tissues of mice. In addition, our current study also demonstrated that dietary CLA increased mRNA expression of genes and enzymes involved in fatty acid synthesis and lipid metabolism the muscle tissues of mice. These findings suggest that CLA mainly increases the expression of A-FABP through PPARα signaling pathway and regulates the expression of genes and enzymes related to IMF deposition, thus increasing IMF content. These results contribute to better understanding the molecular mechanism of IMF accretion in animals for the improvement of meat quality.

Relationships between adipocyte fatty acid-binding protein with parameters of obesity in women with polycystic ovary syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Inhibitory Effects of Hydrolysable Tannins on Lipid Accumulation in 3T3-L1 Cells.

Obesity is currently the most common cause of metabolic diseases including type 2 diabetes and hyperlipidemia. Obesity results from excess lipid accumulation in adipose tissue. Several studies have investigated the inhibitory effects of natural plant-derived products on adipocyte differentiation and lipid accumulation. In this study, we examined the effect of hydrolysable tannins composed of gallic acid and glucose on adipocyte differentiation in 3T3-L1 cells. 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (PGG) (1), a representative gallotannin, inhibited lipid accumulation in 3T3-L1 cells, whereas ellagitannins (tellimagrandin I, eugeniin and casuarictin) did not. The expression of adipocyte differentiation-related genes, including peroxisome proliferator activator γ2 (Pparγ2), CCAAT/enhancer binding protein α (C/EBPα) and adipocyte fatty acid binding protein (aP2), was significantly suppressed in PGG (1)-treated 3T3-L1 cells beginning at day 2 after induction of differentiation. While PGG (1) did not directly reduce Pparγ2 expression, it reduced the expression of its target genes in mature adipocytes. In addition, PGG (1) treatment inhibited mitotic clonal expansion, one of earliest events of adipocyte differentiation. These findings indicate that PGG (1) has an inhibitory effect on adipocyte differentiation through the suppression of mitotic clonal expansion.

Inhibitory Effect of Bacterial Lysates Extracted from Pediococcus acidilactici on the Differentiation of 3T3-L1 Pre-Adipocytes.

Postbiotics, including bacterial lysates, are considered alternatives to probiotics. The aim of the current study was to investigate the effect of bacterial lysates (BLs) extracted from Pediococcus acidilactici K10 (K10 BL) and P. acidilactici HW01 (HW01 BL) on the differentiation of 3T3-L1 pre-adipocytes. Both K10 and HW01 BLs significantly reduced the accumulation of lipid droplets and the amounts of cellular glycerides in 3T3-L1 cells (p < 0.05). However, another postbiotic molecule, peptidoglycan of P. acidilactici K10 and P. acidilactici HW01, moderately inhibited the accumulation of lipid droplets, whereas heat-killed P. acidilactici did not effectively inhibit the lipid accumulation. The mRNA and protein levels of the transcription factors, peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α, responsible for the differentiation of 3T3-L1 cells, were significantly inhibited by K10 BL and HW01 BL (p < 0.05). Both K10 and HW01 BLs decreased adipocyte-related molecules, adipocyte fatty acid-binding protein and lipoprotein lipase, at the mRNA and protein levels. Furthermore, both K10 and HW01 BLs also downregulated the mRNA expression of leptin, but not resistin. Taken together, these results suggest that P. acidilactici BLs mediate anti-adipogenic effects by inhibiting adipogenic-related transcription factors and their target molecules.

Changes in the triglyceride metabolism in the thigh muscle and liver of broilers injected intravenously with angiopoietin-like protein 4

Angiopoietin-like protein 4 (ANGPTL4) is a potential circulating mediator connecting nutritional factors and fat metabolism, however, information is lacking on the exact role of ANGPTL4 on triglyceride metabolism in the thigh muscles and livers of broilers. The objective of this study was to determine the changes in the triglyceride metabolism in the thigh muscles and livers of broilers injected intravenously with ANGPTL4. In experiment 1, 36 male Arbor Acres broilers at 35 days of age were randomly allocated into six treatments with six replicates. The broilers were subjected to intravenous injection of polyhistidine-small ubiquitin-related modifier-ANGPTL4 (His-SUMO-ANGPTL4) once at a dose of 0, 20, 100, 500, 2 500, or 12 500 ng/kg body weight (BW), respectively. The results showed that the injection of His-SUMO-ANGPTL4 at a dose of 500, 2 500 and 12 500 ng/kg BW decreased (P &amp;lt; 0.05) the broilers’ heart-fatty acid-binding protein (H-FABP) mRNA expression in the thigh muscle. All of the His-SUMO-ANGPTL4 broiler injected groups had a lower (P &amp;lt; 0.05) adipocyte-fatty acid-binding protein mRNA expression in the thigh muscle. In experiment 2, 18 male Arbor Acres broilers at 35 days of age were randomly allocated into three treatments with six replicates. The broilers were given an injection of normal saline (NS), His-SUMO, or His-SUMO-ANGPTL4 (500 ng/kg BW) once. The results showed that the broilers receiving an injection of ANGPTL4 at a dose of 500 ng/kg BW decreased (P &amp;lt; 0.05) the H-FABP mRNA expression in the thigh muscle. Besides, the broilers given an injection of ANGPTL4 at a dose of 500 ng/kg BW increased (P &amp;lt; 0.05) the fatty acid synthase mRNA expression and activity and decreased (P &amp;lt; 0.05) the microsomal triglyceride transfer protein mRNA expression in the liver. However, the concentrations of the high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, insulin, growth hormone and leptin in the serum were not affected by the ANGPTL4 injection. In conclusion, ANGPTL4 has the ability to change the triglyceride metabolism in the thigh muscles and livers of broilers.