Serum Fatty Acid-Binding Protein 4 is Increased in Patients with Psoriasis

Psoriasis is associated with metabolic syndrome and cardiovascular disease. Fatty acid‐binding proteins (FABP) have been recognized as predictors of these systemic disorders. The aim of this study was to assess correlations between levels of serum heart and adipocyte fatty acid‐binding proteins (FABP3, FABP4) and disease severity, indicators of inflammation or metabolic disturbances, and topical treatment in psoriatic patients. Thirty‐seven patients with relapse of plaque‐type psoriasis and 16 healthy volunteers were recruited. Blood samples were collected before and after 14 days of therapy. Serum FABP concentrations were examined by enzyme‐linked immunosorbent assay for correlation with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory or metabolic parameters, and treatment used. The median FABP4 serum levels were significantly increased (p = 0.038) in psoriatic patients, while FABP3 levels did not differ (p = 0.47) compared to the controls. No significant correlations were noted between the proteins and PASI, C‐reactive protein (CRP), BMI, or levels of glucose or lipids. FABP3 significantly correlated with white blood count (p = 0.03) and aspartate aminotransferase (p = 0.04). After topical treatment, there was no significant change in serum FABP3 [11.5 (4.9–30.3) vs. 12.9 (3.5–30.3) ng/ml] (p = 0.96), whereas FABP4 was decreased [27,286 (20,344–32,257) vs. 23,034 (18,320–29,874) pg/ml] (p = 0.12), losing its basal significance. FABP4 may be a marker of psoriasis, and FABP3 may be associated with inflammation or liver disorders in psoriatic patients. FABP do not appear to be useful for determining disease severity or the effectiveness of antipsoriatic treatment.     

A Distinct Cytokine Profile and Stromal Vascular Fraction Metabolic Status without Significant Changes in the Lipid Composition Characterizes Lipedema

Lipedema is an adipose tissue disorder characterized by the disproportionate increase of subcutaneous fat tissue in the lower and/or upper extremities. The underlying pathomechanism remains unclear and no molecular biomarkers to distinguish the disease exist, leading to a large number of undiagnosed and misdiagnosed patients. To unravel the distinct molecular characteristic of lipedema we performed lipidomic analysis of the adipose tissue and serum of lipedema versus anatomically- and body mass index (BMI)-matched control patients. Both tissue groups showed no significant changes regarding lipid composition. As hyperplastic adipose tissue represents low-grade inflammation, the potential systemic effects on circulating cytokines were evaluated in lipedema and control patients using the Multiplex immunoassay system. Interestingly, increased systemic levels of interleukin 11 (p = 0.03), interleukin 28A (p = 0.04) and interleukin 29 (p = 0.04) were observed. As cytokines can influence metabolic activity, the metabolic phenotype of the stromal vascular fraction was examined, revealing significantly increased mitochondrial respiration in lipedema. In conclusion, despite sharing a comparable lipid profile with healthy adipose tissue, lipedema is characterized by a distinct systemic cytokine profile and metabolic activity of the stromal vascular fraction.     

Association of L‐FABP T94A and MTP I128T Polymorphisms with Hyperlipidemia in Chinese Subjects

The purpose of this study was to evaluate the relation between the L‐FABP T94A and MTP I128T polymorphisms and hyperlipidemia in Chinese subjects. We recruited 390 volunteers: 201 hyperlipidemic and 189 healthy volunteers. The L‐FABP T94A and MTP I128T polymorphisms were genotyped using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Anthropometry, lipid profile, and liver function of the subjects were determined. We observed that male carriers of the L‐FABP A94 allele had significantly higher body weight (P = 0.012), higher body mass index (BMI) (P = 0.014), and higher plasma triacylglycerol levels (TAG) (P = 0.033) and lower ratios of high‐density lipoprotein cholesterol (HDL‐C) to total cholesterol (TC) (P = 0.008) than T94 homozygotes. The MTP T128 allele was associated with significantly lower serum TC (P < 0.001) and low‐density lipoprotein cholesterol (LDL‐C) (P < 0.001) levels in males. There was a direct correlation between the MTP T128 allele and a decreased risk of hyperlipidemia after adjusting for body mass index (OR = 0.327, 95 % CI: 0.178–0.600, P < 0.001). In conclusion, both the MTP I128T and the L‐FABP T94A polymorphisms can affect serum lipid levels in the Chinese population. The MTP T128 allele offers protection against hyperlipidemia in the Chinese population.     

Protective Effects of Voluntary Exercise on Hepatic Fat Accumulation Induced by Dietary Restriction in Zucker Fatty Rats

Weight control based on dietary restriction (DR) alone can cause lipid metabolic failure and progression to fatty liver. This study aimed to investigate the effect of exercise on preventing DR-induced hepatic fat accumulation in Zucker fatty (ZF) rats by focusing on the relationship between adipose tissue lipolysis and hepatic fat uptake. Six-week-old male ZF rats were randomly assigned to obese, DR, or DR with exercise (DR + Ex) groups. The DR and DR + Ex groups were fed a restricted diet, with the latter also undergoing voluntary exercise. After 6 weeks, hepatic fat accumulation was observed in the DR group, whereas intrahepatic fat was markedly reduced in the DR + Ex group. Compared with the obese (Ob) group, the DR group exhibited 2.09-fold expression of hepatic fatty acid translocase (FAT)/CD36 proteins (p < 0.01) and 0.14-fold expression of hepatic fatty acid-binding protein (FABP)1 (p < 0.01). There were no significant differences between the DR + Ex group and the Ob group. FAT/CD36 and hepatic triglyceride (TG) expression levels were strongly positively correlated (r = 0.81, p < 0.001), whereas there was a strong negative correlation between FABP1 and hepatic TG expression levels (r = −0.65, p < 0.001). Our results suggest that hepatic fat accumulation induced by DR in ZF rats might be prevented through exercise-induced modifications in FAT/CD36 and FABP1 expression.     

Common FABP4 Genetic Variants and Plasma Levels of Fatty Acid Binding Protein 4 in Older Adults

We examined common variants in the fatty acid binding protein 4 gene (FABP4) and plasma levels of FABP4 in adults aged 65 and older from the Cardiovascular Health Study. We genotyped rs16909187, rs1054135, rs16909192, rs10808846, rs7018409, rs2290201, and rs6992708 and measured circulating FABP4 levels among 3190 European Americans and 660 African Americans. Among European Americans, the minor alleles of six single nucleotide polymorphisms (SNP) were associated with lower FABP4 levels (all p ≤ 0.01). Among African Americans, the SNP with the lowest minor allele frequency was associated with lower FABP4 levels (p = 0.015). The C-A haplotype of rs16909192 and rs2290201 was associated with lower FABP4 levels in both European Americans (frequency = 16 %; p = 0.001) and African Americans (frequency = 8 %; p = 0.04). The haplotype combined a SNP in the first intron with one in the 3′untranslated region. However, the alleles associated with lower FABP4 levels were associated with higher fasting glucose in meta-analyses from the MAGIC consortium. These results demonstrate associations of common SNP and haplotypes in the FABP4 gene with lower plasma FABP4 but higher fasting glucose levels.     

Circulating Adipokine VASPIN Is Associated with Serum Lipid Profiles in Humans

VASPIN, visceral adipose tissue-derived serpin, is an adipokine ameliorating insulin resistance in obesity. Here, we investigated the role of VASPIN and its genetic variants in lipid metabolism. We measured serum VASPIN concentrations by ELISA in 823 metabolically well-characterized Caucasian subjects (Sorbs from Germany). Furthermore, we genotyped 30 representative single nucleotide polymorphisms (SNP) in two independent cohorts with metabolic phenotyping, the Sorbs (N = 823) and Leipzig (N = 919), and conducted genotype–phenotype association analyses. Circulating VASPIN strongly correlated with triacylglycerol levels (TAG; p = 1.079 × 10⁻¹¹), and moderately with apolipoprotein A1 and low-density lipoprotein cholesterol (p = 0.026). Genetic variants in VASPIN were nominally associated with cholesterol, high-density and low-density lipoprotein (HDL-chol, LDL-chol), lipoprotein A, and apolipoprotein B as well as with TAG and free fatty acids (all p < 0.05 adjusted for age, sex, and body mass index [BMI]). Mendelian randomization analysis using VASPIN SNP as an instrumental variable showed borderline influence of VASPIN on LDL-chol levels (p = 0.05). Associations of VASPIN and its genetic variation with metabolic traits suggest a role of VASPIN in human lipid metabolism.     

Conjugated Linoleic Acid Isomers Trans‐10, Cis‐12 and Cis‐9, Trans‐11 Prevent Collagen‐Induced Arthritis in a Direct Comparison

Mixed‐isomer conjugated linoleic acid (CLA) and the individual isomers, trans‐10, cis‐12 (CLAt10c12) and cis‐9, trans‐11 (CLAc9t11), decrease severity of collagen‐induced arthritis (CA) when consumed after disease onset. Few studies have been conducted exploring the role of CLA in the prevention of autoimmune diseases. These studies suggest that isomer‐specific effects may be occurring; however, a direct comparison of CLAt10c12 and CLAc9t11 has yet to be conducted. A study to compare the ability of CLAt10c12 and CLAc9t11 to prevent CA and assess their effects on early inflammation was performed. DBA/1 mice were fed a semipurified diet containing 6% corn oil (CO), 5.5% CO and 0.5% CLAt10c12, or 5.5% CO and 0.5% CLAc9t11 (n = 27 per diet) starting three weeks before CA primary immunization. Effects on disease incidence and severity, anticollagen antibodies, plasma and paw cytokines, and hepatic fatty acids were measured. Arthritis incidence was reduced by a minimum of 34% in mice fed either CLA isomer compared to those fed CO diet (p = 0.06). In mice that did develop arthritis (n = 9–12 mice per treatment), CLAt10c12 reduced arthritic severity to a greater extent than CLAc9t11 and CO (p = 0.03). CLA isomer treatment attenuated the increased hepatic arachidonic acid (ARA; 20:4n‐6) observed with arthritis at one‐week postonset (p = 0.03), while no differences in anticollagen antibodies or cytokines were observed between dietary treatments. These results suggest that CLA isomers may be effective at preventing specific immune‐mediated inflammatory diseases, in part, through modulation of the ARA cascade.     

Metabolic Profiles of Brain Metastases

Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49) were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01), irrespective of their primary origin. The principal component analysis (PCA) showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01), indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.     

Serum Interleukin-18, Fetuin-A,Soluble Intercellular Adhesion Molecule-1, and Endothelin-1 in Ankylosing Spondylitis,Psoriatic Arthritis,and SAPHO Syndrome

To examine serum interleukin 18 (IL-18), fetuin-A, soluble intercellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) levels in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and Synovitis Acne Pustulosis Hyperostosis Osteitis syndrome (SAPHO). We studied 81 AS, 76 PsA, and 34 SAPHO patients. We measured serum IL-18, fetuin-A, sICAM-1, ET-1, IL-6, IL-23, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). IL-18 levels were higher in AS (p = 0.001), PsA (p = 0.0003), and SAPHO (p = 0.01) than in controls, and were positively correlated with CRP (p = 0.03), VEGF (p = 0.03), and total cholesterol (TC, p = 0.006) in AS and with IL-6 (p = 0.03) in PsA. Serum fetuin-A levels were lower in AS (p = 0.001) and PsA (p = 0.001) than in controls, and negatively correlated with C-reactive protein (CRP) in AS (p = 0.04) and SAPHO (p = 0.03). sICAM-1 positively correlated with CRP (p = 0.01), erythrocyte sedimentation rate (ESR, p = 0.01), and IL-6 (p = 0.008) in AS, and with IL-6 (p = 0.001) in SAPHO. Serum ET-1 levels were lower in AS (p = 0.0005) than in controls. ET-1 positively correlated with ESR (p = 0.04) and Disease Activity Score 28 (DAS28, p = 0.003) in PsA. In spondyloarthritis, markers of endothelial function correlated with disease activity and TC.     

Ligand Binding Promiscuity of Human Liver Fatty Acid Binding Protein: Structural and Dynamic Insights from an Interaction Study with Glycocholate and Oleate

Human liver fatty acid binding protein (hL‐FABP) has been reported to act as an intracellular shuttle of lipid molecules, thus playing a central role in systemic metabolic homeostasis. The involvement of hL‐FABP in the transport of bile salts has been postulated but scarcely investigated. Here we describe a thorough NMR investigation of glycocholate (GCA) binding to hL‐FABP. The protein molecule bound a single molecule of GCA, in contrast to the 1:2 stoichiometry observed with fatty acids. GCA was found to occupy the large internal cavity of hL‐FABP, without requiring major conformational rearrangement of the protein backbone; rather, this led to increased stability, similar to that estimated for the hL‐FABP:oleate complex. Fast‐timescale dynamics appeared not to be significantly perturbed in the presence of ligands. Slow motions (unlike for other proteins of the family) were retained or enhanced upon binding, consistent with a requirement for structural plasticity for promiscuous recognition.     

Short‐Chain Fatty Acids Enhance the Lipid Accumulation of 3T3‐L1 Cells by Modulating the Expression of Enzymes of Fatty Acid Metabolism

Short‐chain fatty acids (SCFA) such as acetic acid, propionic acid, and butyric acid are produced by fermentation by gut microbiota. In this paper, we investigate the effects of SCFA on 3T3‐L1 cells and the underlying molecular mechanisms. The cells were treated with acetic acid, propionic acid, or butyric acid when cells were induced to differentiate into adipocytes. MTT assay was employed to detect the viability of 3T3‐L1 cells. Oil Red O staining was used to visualize the lipid content in 3T3‐L1 cells. A triglyceride assay kit was used to detect the triacylglycerol content in 3T3‐L1 cells. qRT‐PCR and Western blot were used to evaluate the expression of metabolic enzymes. MTT results showed that safe concentrations of acetic acid, propionic acid, and butyric acid were less than 6.4, 3.2, and 0.8 mM, respectively. Oil Red O staining and triacylglycerols detection results showed that treatment with acetic acid, propionic acid, and butyric acid accelerated the 3T3‐L1 adipocyte differentiation. qRT‐PCR and Western blot results showed that the expressions of lipoprotein lipase (LPL), adipocyte fatty acid binding protein 4 (FABP4), fatty acid transporter protein 4 (FATP4), and fatty acid synthase (FAS) were significantly increased by acetic acid, propionic acid, and butyric acid treatment during adipose differentiation (p < 0.05). In conclusion, SCFA promoted lipid accumulation by modulating the expression of enzymes of fatty acid metabolism.     

Fat Distribution and Lipid Profile of Young Adults with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Enzyme Deficiency

We aimed to compare detailed fat distribution and lipid profile between young adults with congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency and a control group. We also verified independent associations of treatment duration and daily hydrocortisone dose equivalent (HDE) with lipid profile within patients. This case–control study included 23 patients (7 male and 16 female) matched by an age range of young adults (18–31 years) with 20 control subjects (8 male and 12 female). Dual energy X-ray absorptiometry was used to measure the fat distribution. Male patients demonstrated elevated indices of fat mass for total (7.7 ± 2.1 vs. 4.5 ± 1.3 kg/m², p = 0.003), trunk (4.0 ± 1.2 vs. 2.2 ± 0.8 kg/m², p = 0.005), android (0.63 ± 0.24 vs. 0.32 ± 0.15 kg/m², p = 0.008), gynoid (1.34 ± 0.43 vs. 0.74 ± 0.24 kg/m², p = 0.005), arm (0.65 ± 0.16 vs. 0.39 ± 0.10 kg/m², p = 0.009), and leg regions (2.7 ± 0.8 vs. 1.6 ± 0.4 kg/m², p = 0.005) than the control group, but not in females. However, female patients demonstrated elevated ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (1.90 ± 0.46 vs. 1.39 ± 0.47, p = 0.009) than the control group, but not in males. Total fat mass was inversely correlated with total testosterone (r = −0.64, p = 0.014) and positively correlated with leptin in males (r = 0.75, p = 0.002). An elevated daily HDE (β = 0.43, p = 0.038 and β = 0.47, p = 0.033) and trunk to total fat mass ratio (β = 0.46, p = 0.025, and β = 0.45, p = 0.037) were independently correlated with impaired lipid profile markers. Although there is no altered lipid profile, male patients demonstrated an increased fat distribution. However, female patients presented with an impaired lipid profile marker but demonstrated close values of normal fat distribution. Interestingly, the dose of glucocorticoid therapy can have some role in the lipid mechanisms.     

Prognostic Value of Preoperative Serum Levels of Periostin (PN) in Early Breast Cancer (BCa)

PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005), adjuvant systemic therapy (p = 0.04) and progesterone receptor (PgR) status (p = 0.02). No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05) and in those with a low PgR expression (p = 0.03). Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04). Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients.     

Changes in cholesteryl ester transfer protein concentration during normal gestation

Background: It has been shown that endogenous estrogen may affect the concentration of cholesteryl ester transfer protein (CETP) and that the gestation in women is accompanied by increased levels of endogenous estrogen. Objectives: To examine the changes in CETP concentration and to investigate the relationship between CETP and estrogen levels during normal pregnancy. Methods: Serum concentrations of CETP, estrogen and lipid traits were determined from 296 healthy women at different times during gestation. Results: Pregnant women exhibited a significant elevation in the concentration of CETP as compared with non‐pregnant women (3.11 ± 1.51 mg/L vs. 2.64 ± 1.25 mg/L, p <0.001). The CETP concentration was highest in the first trimester (3.85 ± 1.33 mg/L, compared with controls, p <0.0001), declined progressively from the first to the third trimester and still remained elevated in the third trimester as compared with non‐pregnant subjects (p <0.05). A negative correlation was noted between serum CETP and estradiol (E₂) levels in pregnant women (r = –0.288, p <0.0001). In addition, significantly negative correlations between the serum CETP concentration and all the lipid traits examined were found in gestating women. Conclusion: CETP concentrations were significantly elevated in pregnancy and decreased progressively from early to late gestation. The results suggest that endogenous E₂ is either not involved or its effect on CETP is dominated by elevated lipid levels or some other factors during mid and late pregnancy.     

Plasma Phospholipid Fatty Acid Profile is Altered in Both Septic and Non-Septic Critically Ill: A Correlation with Inflammatory Markers and Albumin

This study analyzes fatty acid (FA) composition in plasma lipids and erythrocyte phospholipids while comparing septic and non‐septic critically ill patients. The aim was to describe impacts of infection and the inflammatory process. Patients with severe sepsis (SP, n = 13); age‐, sex‐ and APACHE II score‐matched non‐septic critically ill with systemic inflammatory response syndrome (NSP, n = 13); and age‐/sex‐matched healthy controls (HC, n = 13) were included in a prospective case–control study during the first 24 h after admission to the intensive care unit. In both SP and NSP, lower n‐6 polyunsaturated FA (PUFA) accompanied by higher proportions of monounsaturated FA (MUFA) in plasma phospholipids (PPL) was observed relative to HC. MUFA proportion was negatively correlated with n‐6 PUFA, high density lipoprotein cholesterol (HDL‐C), and albumin. MUFA was positively correlated with C‐reactive protein (CRP), procalcitonin (PCT), interleukins (IL‐6, IL‐10), oxidized low density lipoproteins (ox‐LDL), and conjugated dienes (CD). In both SP and NSP, inflammatory and lipid peroxidation markers were significantly higher—CRP (p < 0.001; p = 0.08), IL‐6, IL‐10, TNF‐α (p < 0.01, p = 0.06), ox‐LDL, and CD while total cholesterol, HDL‐C, LDL‐C albumin, and 20:4n‐6/22:6n‐3 and n‐6/n‐3 ratios were lower compared to HC. In conclusion, the changes in plasma lipid FA profile relate to the intensity of inflammatory and peroxidative response regardless of insult etiology. The lower MUFA and higher n‐6 PUFA proportions in PPL were inversely correlated with cholesterol and albumin levels.     

The Effect of Far-Infrared Therapy on the Peritoneal Expression of Glucose Degradation Products in Diabetic Patients on Peritoneal Dialysis

Peritoneal dialysis (PD) is a treatment modality for end-stage renal disease (ESRD) patients. Dextrose is a common osmotic agent used in PD solutions and its absorption may exacerbate diabetes mellitus, a common complication of ESRD. PD solutions also contain glucose degradation products (GDPs) that may lead to encapsulating peritoneal sclerosis (EPS), a severe complication of PD. A previous study showed that far-infrared (FIR) therapy improved a patient’s gastrointestinal symptoms due to EPS. Due to limited literature on the matter, this study aims to investigate dialysate GDPs and peritoneal function in diabetic patients on PD. Thirty-one PD patients were enrolled and underwent 40 min of FIR therapy twice daily for six months. We demonstrated the effect of FIR therapy on the following: (1) decrease of methylglyoxal (p = 0.02), furfural (p = 0.005), and 5-hydroxymethylfurfural (p = 0.03), (2) increase of D/D0 glucose ratio (p = 0.03), and (3) decrease of potassium levels (p = 0.008) in both DM and non-DM patients, as well as (4) maintenance and increase of peritoneal Kt/V in DM and non-DM patients, respectively (p = 0.03). FIR therapy is a non-invasive intervention that can decrease dialysate GDPs in PD patients by improving peritoneal transport rate and solute removal clearance, while also maintaining dialysis adequacy.     

Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.     

Impact of Fabp1 Gene Ablation on Uptake and Degradation of Endocannabinoids in Mouse Hepatocytes

Liver fatty‐acid‐binding protein (FABP1, L‐FABP) is the major cytosolic binding/chaperone protein for both precursor arachidonic acid (ARA) and the endocannabinoid (EC) products N‐arachidonoylethanolamine (AEA) and 2‐arachidonoylglycerol (2‐AG). Although FABP1 regulates hepatic uptake and metabolism of ARA, almost nothing is known regarding FABP1’s impact on AEA and 2‐AG uptake, intracellular distribution, and targeting of AEA and 2‐AG to degradative hepatic enzymes. In vitro assays revealed that FABP1 considerably enhanced monoacylglycerol lipase hydrolysis of 2‐AG but only modestly enhanced AEA hydrolysis by fatty‐acid amide hydrolase. Conversely, liquid chromatography–mass spectrometry of lipids from Fabp1 gene‐ablated (LKO) hepatocytes confirmed that loss of FABP1 markedly diminished hydrolysis of 2‐AG. Furthermore, the real‐time imaging of novel fluorescent NBD‐labeled probes (NBD‐AEA, NBD‐2‐AG, and NBD‐ARA) resolved FABP1’s impact on uptake vs intracellular targeting/hydrolysis. FABP1 bound NBD‐ARA with 2:1 stoichiometry analogous to ARA, but bound NBD‐2‐AG and NBD‐AEA with 1:1 stoichiometry—apparently at different sites in FABP1’s binding cavity. All three probes were taken up, but NBD‐2‐AG and NBD‐AEA were targeted to lipid droplets. LKO reduced the uptake of NBD‐ARA as expected, significantly enhanced that of NBD‐AEA, but had little effect on NBD‐2‐AG. These data indicated that FABP1 impacts hepatocyte EC levels by binding EC and differentially impacts their intracellular hydrolysis (2‐AG) and uptake (AEA).