Serum Free Fatty Acid Levels Research Articles

Roles of extrahepatic lipolysis and the disturbance of hepatic fatty acid metabolism in TNF-α -induced hepatic steatosis

Our previous study showed that both Kupffer cell eliminator (GdCl3) and tumor necrosis factor α (TNF-α) receptor antagonist (etanercept) could partially attenuate binge drinking-induced liver steatosis. Herein, we extended the study by directly investigating the roles of TNF-α on the hepatic fat levels in mice and in HepG2 cells, and explored the underlying mechanisms. SPF male ICR mice were exposed to TNF-α (0.166 mg/kg body weight) with or without phenylisopropyl adenosine (PIA, an anti-lipolytic drug) for 1.5, 3, 6, and 24 h. We found that TNF-α treatment resulted in hepatic triglyceride (TG) elevation at 6 h time point, which was blocked by PIA. TNF-α led to the activation of extrahepatic lipolysis demonstrated by the increase of serum free fatty acid (FFA) level, and the increased protein levels of adipose triglyceride lipase (ATGL) and phosphorylated hormone-sensitive lipase (HSL) in mice epididymal adipose tissues, but had no significant effects on the protein levels of sterol regulatory element binding protein 1c (SREBP-1c) and peroxisomal proliferator activation receptor α (PPAR-α) in mice liver. The in vitro study showed TNF-α treatment could not result in elevation of TG in HepG2 cells, although it indeed brought about a slight activation of SREBP-1c. These results support the hypothesis that TNF-α might make a small contribution to ethanol-induced fatty liver by stimulating extrahepatic lipolysis.

Palmitate-induced lipotoxicity is crucial for the pathogenesis of nonalcoholic fatty liver disease in cooperation with gut-derived endotoxin

Although previous studies have indicated important roles of palmitate, a saturated fatty acid, in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), it remains unclear how palmitate contributes to inflammation and fibrosis in the liver. Administration of palmitate in high fat diet (HFD)-fed but not basal diet (BD)-fed mice resulted in an increase in serum alanine aminotransferase (ALT) levels. Surprisingly, combined administration of very low dose lipopolysaccharide in palmitate-treated mice led to a marked increase in serum ALT levels despite BD-fed conditions. Administration of palmitate alone in BD-fed mice caused inflammatory cell infiltration and liver fibrosis mediated by the toll-like receptor 4 pathway without ALT elevation. In addition, a significant correlation between serum free fatty acid levels and liver fibrosis stage was observed in patients with NAFLD. These results indicate that palmitate may play crucial roles in the pathogenesis of NAFLD in the presence of gut-derived endotoxin.

Diagnostic value of serum lipoprotein (a) and free fatty acid in patients with type 2 diabetic nephropathy

Objective To investigate the clinical value of serum lipoprotein (a) and free fatty acid (FFA) in the diagnosis of type 2 diabetic nephropathy (DN). Methods From January to October of 2016, 120 cases with type 2 diabetes in the Second People's Hospital of Lianyungang were selected.According to urinary albumin creatinine ratio (UACR), the patients were divided into three groups: normal albuminuria group (NA), microalbuminuria group (MA) and macroalbuminuria group(LA). And 40 healthy subjects were selected as control group.The levels of serum lipoprotein (a) and FFA were measured, and the correlation was analyzed by Pearson analysis.Furthermore, the receiver operating curve was used to evaluate the positive diagnostic rate of DN. Results The levels of lipoprotein (a) in the NA, MA, LA and control group were (212.8±69.0)mg/L, (281.7±70.5)mg/L, (337.2±71.5)mg/L and (187.4±74.0)mg/L, respectively.The levels of lipoprotein (a) in the MA and LA groups were significantly higher than those in the NA and control groups(F=35.08, P<0.05). The levels of FFA in the four groups were (0.63±0.15)mmol/L, (0.84±0.13)mmol/L, (1.07±0.19)mmol/L and (0.47±0.10)mmol/L, respectively.The level of FFA in the DN group was higher than that of the control group, the difference was statistically significant (F=102.13, P<0.05), and increased with the progression of DN.Pearson correlation analysis showed that the serum lipoprotein (a) was positively correlated with FFA (r=0.64, P<0.05). The positive rates of serum lipoprotein (a) and FFA were 64.2% and 73.3% in early diagnosis of DN, the positive rate of combined detection was 84.2% (P<0.05). Conclusion Serum lipoprotein (a) and FFA levels are significantly increased in diabetic patients with renal injury.Both of them have important clinical value in early diagnosis of type 2 DN. Key words: Diabetic nephropathy; Lipoprotein (a); Free fatty acid

Adipocyte Lipolysis Triggers CD11c-ATM Inflammation in Lean Females and Obese Males and Females

Men and post-menopausal women are at greater risk for cardiovascular diseases and diabetes than younger women. In obese rodent models, males exhibit profound adipose tissue macrophage (ATM) accumulation in gonadal white adipose tissue (GWAT) linked to insulin resistance, while females are protected even with enhanced adiposity. We hypothesize that these inflammatory differences may be a result of altered lipolysis responses and that females would have enhanced ATM accumulation when lipolysis is induced. Lipolysis was stimulated with a beta3 adrenergic receptor (ADRB3) agonist CL-316, 243 in C57Bl6/j male and female mice fed 16 weeks of 60% high fat diet (HFD). GWAT leukocytes were isolated after 18 h and evaluated by flow cytometry. Lipogenic, lipolytic, oxidative and inflammatory gene expression along with immunofluorescence were performed. ADRB3 activation did not alter adipose tissue weights, but significantly reduced liver weights in obese females. Obese CL treated female mice showed elevated serum free fatty acid (FFA) and triglyceride (TG) levels compared to levels induced in males. Lipid overload impaired TG storage and utilization genes- Lpl, Fasn, Acsl1, Hsl, and Glut4 expression in obese females. Lipolysis promoted appearance of crown like structures (CLS) in males and females but only induced Il6 proinflammatory cytokine and Mcp1 chemokine expression in obese female GWAT. Activated lipolysis triggered CD11c- ATM accumulation in lean females but in both obese male and female GWAT. Obese males showed a marked reduction in GWAT dendritic cells (DC) but a significant reduction in both GWAT and inguinal WAT DCs of obese females. While obese females are resistant to inflammation, this study shows that induced lipolysis elevates FFA levels, alters lipid metabolism and increased CD11c- ATMs and CLSs in obese females. Elucidating the link between lipolysis and inflammation can better explain sex differences in overall metabolic health leading to targeted treatment strategies. Disclosure M. Varghese: None. S. Abrishami: None. K. Singer: None.

Associations between hypertension and the peroxisome proliferator-activated receptor-\u03b4 (PPARD) gene rs7770619 C>T polymorphism in a Korean population

BackgroundOxidative stress is associated with the increased risk of hypertension (HTN). This cross-sectional study is aimed to identify the association between the peroxisome proliferator-activated receptor-δ (PPARD) polymorphism and plasma malondialdehyde (MDA), an oxidative stress marker which is related to HTN development, and to determine whether PPARD gene is a candidate gene for HTN.ResultsOne thousand seven hundred ninety-three individuals with normal blood pressure (BP) and HTN were included in this cross-sectional study. The Korean Chip was used to obtain genotype data. Through the analysis, the ten most strongly associated single-nucleotide polymorphisms (SNPs) were nominated for an MDA-related SNP. Among them, the rs7770619 polymorphism was identified in the PPARD gene. The CT genotype of the PPARD rs7770619 C>T polymorphism was associated with a lower risk of HTN before and after adjustments for age, sex, body mass index, smoking, and drinking. Significant associations were observed between plasma MDA and the PPARD rs7770619 C>T polymorphism and between systolic BP and the PPARD rs7770619 SNP in the controls. The CT controls showed significantly lower systolic BP and plasma MDA than the CC controls. Additionally, in both controls and HTN patients, the CT subjects showed significantly lower serum glucose and higher adiponectin levels than the CC subjects. Furthermore, the CT subjects showed significantly higher serum free fatty acid levels than the CC subjects among the HTN patients.ConclusionThis is a new finding that the PPARD rs7770619 C>T SNP is a novel candidate variant for HTN based on the association between PPARD and plasma MDA in a Korean population.

A study on the relationship between waist phenotype, hypertriglyceridemia, coronary artery lesions and serum free fatty acids in adult and elderly patients with coronary diseases

BackgroundAbdominal obesity is an independent risk factor for coronary heart disease (CHD) and high serum triglyceride (TG) and free fatty acid levels may precipitate or aggravate CHD.MethodsWe enrolled patients with coronary heart disease in our hospital from October 2008 to July 2009. Patients with high TG and increased WC, i.e. waist phenotype WP were included in group A. In group B, were included patients with high TG but not WP. Group C consisted of patients with WP but not high TG. Finally, Group D was composed of patients without high TG or WP. Serum FFA levels for all patients were measured by ELISA. The relationship between TG levels, WC, FFA levels, and coronary artery score was analysed by a single variable regression.ResultsGroup A had a significantly higher FFA level than the other groups. Regression analysis showed that FFA, TG, WC, hip circumference, waist-to-height ratio, systolic blood pressure, pulse pressure index, and low-density lipoprotein cholesterol all positively correlated with CAS (r = 0.160 ~ 0.415, P = 0.000 ~ 0.032). After we controlled for traditional risk factors for cardiovascular disease, FFA levels remained positively correlated to the CAS (r = 0.365, P < 0.001).ConclusionThe serum FFA level for patients with complications of both increased WC and high TG levels was significantly higher than that of patients without either of these complications. The close correlation between the CAS and FFA levels showed by regression analysis suggested that inflammation in these patients was more serious. Increased WC and high TG levels as well as FFA level are valuable for the prediction of cardiovascular disease and can be applied as a clinical guidance for early intervention in the treatment of coronary heart diseases.

Jelly-type carbohydrate supplement in healthy subjects suppresses the catabolism of adipose tissue and muscle protein and improves their satisfactions

Summary Background & aims Many studies have reported the effects of preoperative clear fluid carbohydrate supplements; however, few studies have reported the effects of preoperative jelly-type carbohydrate supplements. This study aimed to assess the effect of a jelly-type oral nutritional supplement (ONS) on metabolism, redox balance by using various surrogate markers and to evaluate its excretion from the stomach. Methods This study was conducted according to a crossover design. Participants underwent a control experiment whereby they fasted after dinner and only ingested water until the experiment. The remaining participants underwent an ONS experiment whereby they ingested 400 g of ONS before bed and another 400 g at 7:00 am. Blood samples were collected at 9:00 am. After a break of at least 24 h, participants underwent the alternate experiment. Results Thirty minutes after intake of jelly, the gastric antrum appeared flat (the same result as that at baseline) on ultrasonography. The ONS group showed significantly lower serum free fatty acid levels (100 μEq/L, p = 0.027, vs. 327 μEq/L, n = 6), total ketone bodies levels, 3-MH/creatinine levels, and oxidative stress surrogate markers. Serum insulin levels were significantly higher and participant's satisfaction was improved in the ONS group. Conclusions We have the limitations of our methodologies as surrogate markers, compared with direct measurement of lipolysis, proteolysis and redox balance regulation. But Jelly-type ONS suppresses the catabolism of adipose tissue and muscle protein, decreases oxidative stress and improves patient satisfaction in healthy participants, without any increased risk of aspiration.

Epigallocatechin gallate suppresses hepatic cholesterol synthesis by targeting SREBP-2 through SIRT1/FOXO1 signaling pathway.

This study aims to explore the effect of epigallocatechin gallate (EGCG) on blood lipids, liver lipids, and cholesterol synthesis in hyperlipidemic rats. SREBP-2 transgenic rats were used to investigate the transcriptional level of SREBP-2 regulated by SIRT-1/FOXO1 and the molecular mechanism of rate-limiting enzyme HMGCR that affects cholesterol synthesis. Rat models of hyperlipidemia were established and administered EGCG. Cholesterol synthesis was observed. Enzyme linked immunosorbent assay was used to determine serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), superoxide dismutase (SOD), malondialdehyde (MDA), and T-AOC contents. Hematoxylin-eosin staining and oil red O staining were utilized to observe the histological changes in the liver. Biochemical method was applied to measure serum ALT and AST changes. Western blot assay and qRT-PCR were employed to detect the changes in SIRT1/FOXO1 pathway-related proteins, cholesterol synthesis-related genes, and SREBP-2. EGCG 50mg/kg could obviously decrease the liver weight and liver coefficient, reduce serum TG, TC, LDL-C, and FFA levels (P < 0.05), and increase serum HDL-C levels in hyperlipidemic rats. EGCG could diminish hyperlipidemia-induced liver injury and reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Oil red O staining results demonstrated that the number of red lipid droplets in hepatocytes reduced to varying degrees, especially high-dose EGCG. EGCG remarkably diminished MDA content in the liver with hypercholesterolemia and increased T-AOC and SOD activity. In the model group, SIRT1 expression increased, and FOXO1 expression decreased. EGCG activated SIRT1 and increased FOXO1 expression, whose expression trend was consistent with the fenofibrate group. HMGCR, FDPS, SS, and ABCA1 expression increased, and ACAT2 expression noticeably reduced in SREBP-2+/+ transgenic rats. EGCG could reverse the expression trend of each gene. Simultaneously, EGCG increased FOXO1 expression, and decrease SREBP-2 expression; however, no significant changes in these expression were found in SREBP-2-/- rats. EGCG can alleviate liver injury and oxidative stress in hyperlipidemic rats. EGCG can activate SIRT1, activate FOXO1 protein, regulate SREBP-2 protein, and inhibit hepatic cholesterol synthesis.

Apelin-13 treatment enhances the stability of atherosclerotic plaques.

Apelin is an endogenous peptidergic system which modulates cardiovascular function. Recent studies pointed out a fundamental contribution of apelin on atherosclerosis development; however, such reports revealed contradictory data, and to date, it is difficult to accurately define a beneficial or deleterious role. To better understand apelin function on atherosclerosis, we aimed to investigate apelin-13 treatment effects on atherosclerotic plaques composition. Apolipoprotein E gene-deleted mice were fed on Western-type diet for 11 weeks. Atherosclerotic plaque formation was induced in the carotid artery by a shear stress modifier device, which exposes the same vessel to distinct patterns of shear stress enabling the formation of plaques with different composition. Mice were treated with apelin-13 (2 mg kg-1 day-1 ) or vehicle for the last 3 weeks. Apelin-13 treatment did not alter the lipid content of low shear stress- and oscillatory shear stress-induced plaques in the carotid. However, apelin-13 greatly ameliorated plaque stability by increasing intraplaque collagen content and reducing MMP-9 expression. Furthermore, apelin-13 decreased the infiltration of inflammatory cells (neutrophil and macrophage) and intraplaque reactive oxygen species content. Interestingly, apelin-13 treatment reduced total cholesterol, LDL levels and free fatty acid serum levels, while HDL, triglycerides serum levels were not significantly changed. Apelin-13 treatment for 3 weeks did not alter the lesion size, but it significantly enhanced the stable phenotype of atherosclerotic plaques and improved serum lipid profile. These results indicate that activation of apelin system decreases plaque vulnerability.

Epicardial Fat Thickness and Free Fatty Acid Level are Predictors of Acute Ischemic Stroke with Atrial Fibrillation.

BACKGROUNDIncreased epicardial fat is known to be associated with the presence and chronicity of atrial fibrillation (AF). Free fatty acids (FFAs) are major components of epicardial fat; however, their potential association with AF in ischemic stroke has not been investigated. We aimed to assess the performance of echocardiographic epicardial fat thickness (EFT) and plasma FFA level in identifying patients with ischemic stroke and AF.METHODSWe enrolled a total of 214 consecutive patients (mean age, 66.8 ± 12.3 years; 39.7% women) diagnosed with acute ischemic stroke between March 2011 and June 2014. The patients were divided into two groups: ischemic stroke with AF (n = 35, 16.4%) and ischemic stroke without AF (n = 179, 83.6%).RESULTSThe ischemic stroke with AF group showed significantly higher serum FFA level (1379.7 ± 717.5 vs. 757.8 ± 520.5 uEq/L, p < 0.0001) and EFT (6.5 ± 1.2 vs. 5.3 ± 1.2 mm, p < 0.001) than the group without AF. Multivariable logistic regression analysis demonstrated that age (odds ratio [OR], 1.112), serum FFA level (OR, 1.002), and EFT (OR, 1.740) were independently associated with the ischemic stroke group with AF. EFT and FFA significantly improved the goodness-of-fit and discriminability of the simple regression model including age as a covariate (log likelihood difference, 21.35; p < 0.001; c-index difference, 17.9%; p < 0.001).CONCLUSIONSHigh EFT and serum FFA level were associated with ischemic stroke in patients with AF. Echocardiographic EFT and serum FFA level can play a significant role in identifying ischemic stroke with AF.

Relationships between serum free fatty acid and pulse pressure amplification in overweight/obese men: insights from exercise training and dietary modification.

Pulse pressure amplification (i.e., the ratio of peripheral to central pulse pressure) is a strong predictor of cardiovascular events. Circulating free fatty acid, which is a major cause of insulin resistance, has been reported to favorably be associated with pulse pressure amplification in the arm (from the aorta to brachial artery). We hypothesized that this paradoxical relationship depended on an evaluating site of pulse pressure amplification and investigated whether serum free fatty acid level is related to pulse pressure amplification in the arm or trunk (from the aorta to femoral artery) in overweight/obese men. In a cross-sectional study, 85 men participated, and regression analyses revealed that serum free fatty acid level was significantly and independently associated with pulse pressure amplification in the arm but not the trunk. In a longitudinal study, 33 men completed a 12-week lifestyle intervention that involved both exercise training and dietary modification. The lifestyle intervention-induced change in serum free fatty acid level was significantly correlated to that in pulse pressure amplification in the arm but not the trunk. These results support our hypothesis and suggest that pulse pressure amplification should be measured in the trunk instead of the arm in overweight/obese men to simplify its interpretation.

Qizhi Decoction may Protect Diabetic Nephropathy Through Decrease Lipid and Inflammation

Diabetic nephropathy (DN) affects approximately one-third of individuals with diabetes mellitus. Many patients develop kidney damage despite modern pharmacologic therapies available for DN treatment. Chinese medicine is a good choice for patients with DN. The aim of this study is to study the effect and safety of Qizhi decoction on patients with diabetic nephropathy. Approximately 255 men and women aged ≥18 to ≤80 years with DN were enrolled and randomized to two groups. The experimental intervention accepted Qizhi decoction in addition to their usual Novolin 50R penfill regimen. The control intervention accepted only Novolin 50R penfill. All participants receive their regimen for 12 weeks. Estimated glomerular filtration rate (eGFR), serum free fatty acid (FFA) level, the urine protein/creatinine ratio (U/C), plasma cystatin C (Cyst), Plasma C-reactive protein (CRP), hemoglobin A1c, serum uric acid, dyslipidemia were tested before entering the group. At the end of this study the index above and safety were measured again. Urine albumin levels, U/C, Cyst, CRP, FFA, TNF-α and MCP-1 levels decreased in both groups after 12 weeks of treatment. The eGFR, Cyst improved after12 weeks of treatment. Compared to the control, urine albumin levels, U/C, Cyst, CRP, FFA, TNF-α and MCP-1 levels decreased obviously in treatment group after 12 weeks of treatment. The kidney function, as measured by the eGFR, Cyst, significantly improved after12 weeks of treatment. The results indicate that combined Chinese and western medicine should be the better choice of patients with DN. QZD may protect Diabetic nephropathy through decrease lipid and inflammation.

Exenatide ameliorates hepatic steatosis and attenuates fat mass and FTO gene expression through PI3K signaling pathway in nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with metabolic syndrome and can lead to life-threatening complications like hepatic carcinoma and cirrhosis. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist antidiabetic drug, has the capacity to overcome insulin resistance and attenuate hepatic steatosis but the specific underlying mechanism is unclear. This study was designed to investigate the underlying molecular mechanisms of exenatide therapy on NAFLD. We used in vivo and in vitro techniques to investigate the protective effects of exenatide on fatty liver via fat mass and obesity associated gene (FTO) in a high-fat (HF) diet-induced NAFLD animal model and related cell culture model. Exenatide significantly decreased body weight, serum glucose, insulin, insulin resistance, serum free fatty acid, triglyceride, total cholesterol, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in HF-induced obese rabbits. Histological analysis showed that exenatide significantly reversed HF-induced lipid accumulation and inflammatory changes accompanied by decreased FTO mRNA and protein expression, which were abrogated by PI3K inhibitor LY294002. This study indicated that pharmacological interventions with GLP-1 may represent a promising therapeutic strategy for NAFLD.

Effects of Exogenous Lysolecithin Emulsifier Supplementation on the Growth Performance, Nutrient Digestibility, and Blood Lipid Profiles of Broiler Chickens.

This study aimed to evaluate the effects of dietary supplementation of lysolecithin emulsifier on growth performance, nutrient digestibility, and blood lipid profiles in growing broiler chickens. In total, 1,020 1-day-old male Ross 308 broiler chickens with an average initial live weight of 43±1.2 g were randomly allotted to five dietary treatments for a 35 d experiment. The treatments included: (1) NC, negative control (metabolizable energy (ME)=3,100 kcal/kg for phase 1 and phase 2), (2) PC, positive control (ME=3,200 kcal/kg), (3) T1, NC+0.03% lysolecithin, (4) T2, NC+0.06% lysolecithin, and (5) T3, NC+0.09% lysolecithin. During days 1–35, the feed conversion ratios (FCR) of broiler chickens fed with T2 and T3 diets were lower than those of broiler chickens fed with NC diet (P<0.05). On day 35, the total tract nutrient retention (TTNR) of gross energy and ether extract of broiler chickens fed with PC and T3 diets was higher than those fed with NC diet (P<0.05). However, serum total cholesterol, triglyceride, and free fatty acid levels were not influenced by lysolecithin supplementation. In conclusion, lysolecithin supplementation improved FCR and TTNR of energy and ether extract when broiler chickens were offered a reduced energy diet.

Effect of hemodialysis on serum free fatty acids levels in septic patients with acute renal failure

Zika virus (ZIKV) was first detected in Brazil in May 2015 and the country experienced an explosive epidemic. However, recent studies indicate that the introduction of ZIKV occurred in late 2013. Cases of microcephaly and deaths associated with ZIKV infection were identified in Brazil in November, 2015.To determine the etiology of three fatal adult cases.Here we report three fatal adult cases of ZIKV disease. ZIKV infection in these patients was confirmed by cells culture and/or real-time reverse transcriptase polymerase chain reaction (RT-qPCR) and by antigen detection using immunohistochemical assay. Samples of brain and other selected organs taken at autopsy from three patients were also analyzed by histopathological and immunohistological examination.The first patient, a 36-year-old man with lupus and receiving prednisone therapy, developed a fulminant ZIKV infection. At autopsy, RT-qPCR of blood and tissues was positive for ZIKV RNA, and the virus was cultured from an organ homogenate. The second patient, a previously healthy female, 16 years of age, presented classic symptoms of Zika fever, but later developed severe thrombocytopenia, anemia and hemorrhagic manifestations and died. A blood sample taken on the seventh day of her illness was positive RT-PCR for ZIKV RNA and research in the serum was positive for antinuclear factor fine speckled (1/640), suggesting Evans syndrome (hemolytic anemia an autoimmune disorder with immune thrombocytopenic purpura) secondary to ZIKV infection. The third patient was a 20-year-old woman hospitalized with fever, pneumonia and hemorrhages, who died on 13 days after admission. Histopathological changes were observed in all viscera examined. ZIKV antigens were detected by immunohistochemistry in viscera specimens of patients 1 and 3. These three cases demonstrate other potential complications of ZIKV infection, in addition to microcephaly and Guillain-Barre syndrome (GBS), and they suggest that individuals with immune suppression and/or autoimmune disorders may be at higher risk of developing severe disease, if infected with ZIKV.

Adipose Triglyceride Lipase Gene Polymorphisms is Not Associated with Free Fatty Acid Levels in Chinese Han Population.

Elevated levels of free fatty acids (FFAs) play a role in the pathogenesis of insulin resistance and atherosclerosis. Adipose triglyceride lipase (also defined as patatin-like phospholipase domain containing 2 or PNPLA2) has been demonstrated to contribute to the release of FFA. The aim of this study was to investigate the association of PNPLA2 gene variations with FFA levels in healthy Chinese Han population. Single-nucleotide polymorphisms of PNPLA2 were genotyped using TaqMan method to perform association studies with serum level of FFA and other lipid parameters in 1765 subjects among healthy Chinese Han population. All the subjects were divided into two groups: normal FFAs group (FFAs ≤0.88 mmol/L) and high FFAs group (FFAs >0.88 mmol/L). Neither rs7925131 nor rs7942159 was significantly associated with FFA level. We observed no difference in the genotype frequency of rs7925131 or rs7942159 between the normal FFA group and the high FFA group. Our results do not support an association of rs7925131 or rs7942159 with the FFA levels among the Chinese Han population.

COMP-angiopoietin-1 mitigates changes in lipid droplet size, macrophage infiltration of adipose tissue and renal inflammation in streptozotocin-induced diabetic mice.

Adipose tissue is considered to be an endocrine organ, and adipocyte size correlates with insulin resistance and metabolic parameters in obesity. There is little data on the effects of angiopoietin-1 in adipose tissue and kidney in streptozotocin (STZ)-induced diabetes. In this study, we investigated the protective effect of COMP-angiopoietin-1 (COMP-Ang1), a potent variant of angiopoietin-1, on vascular endothelial cells in epididymal adipose tissue and its regulatory effect on other metabolic parameters, such as lipid droplet diameter, macrophage infiltration, and renal inflammation in STZ-treated mice. Our data showed that COMP-Ang1 increased the density of platelet endothelial cell adhesion molecule-1 (PECAM-1)-1-positive vascular endothelial cells in adipose tissue, which were significantly decreased by treatment with STZ. COMP-Ang1 ameliorated the STZ–induced decrease in lipid droplet diameter and increase in macrophage infiltration in adipose tissue. Serum free fatty acid and triglyceride levels were decreased after administration of COMP-Ang1. There was a beneficial effect on serum insulin levels after treatment with COMP-Ang1 in STZ-induced diabetic mice. Fasting blood glucose levels in COMP-Ang1-treated mice were significantly lower than those of LacZ-treated mice. Cotreatment with COMP-Ang1 and STZ also had similar effects on the above parameters. Administration of soluble Tie2, an inhibitor of angiopoietin-1, reversed the effects of COMP-Ang1. COMP-Ang1 was found to ameliorate the up-regulation of proinflammatory molecules and F4/80-positive macrophage infiltration in the kidneys of STZ-treated mice. COMP-Ang1 increased the phosphorylation of Akt in epididymal adipose tissue and kidneys of STZ-induced diabetic mice. These data indicate that COMP-Ang1 regulates lipogenic effects in adipose tissue and renal inflammation in STZ-induced diabetic mice.

Correlation study on the serum uric acid and free fatty acid levels of Shandong coastal inhabitants

To evaluate the correlation of the serum uric acid and free fatty acid(FFA)levels in Shandong coastal residents. To investigate the correlation between serum uric acid and FFA based on 3 860 individuals who have been long staying in Qingdao, Yantai, Weihai, Rizhao with a randomized, stratified cluster sampling method. According to FFA quartile, subjects were divided into four groups: group Q1 of 908, group Q2 1 016, group Q3 958, and group Q4 978 cases. The prevalence of hyperuricemia and serum uric acid levels increased with the increasing FFA quartile. Compared with Q1, Q2, and Q3 groups, the prevalence of hyperuricemia in Q4 group and the increase of serum uric acid were statistically significant(P<0.05). And in the group Q4, hyperuricemia prevalence is twice as the group A. According to the serum uric acid level, subjects were divided into the normal uric acid group(n=3 331)and the hyperuricemia group(n=529). In the hyperuricemia group, their systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, triglycerides, total cholesterol, low density lipoprotein-cholesterol(LDL-C), glucose, uric acid, FFA, body mass index etc. were significantly higher than those of the normal uric acid group(all P<0.01), while the high density lipoprotein-cholesterol(HDL-C), cystatin, glomerular filtration rate(eGFR)are significantly lower than those of the normal uric acid group(all P<0.01). Serum uric acid levels are positively correlated with systolic and diastolic blood pressures, waist and hip circumferences, triglycerides, total cholesterol, LDL-C, FFA, blood glucose, body mass index(all P<0.01); and negatively correlated with eGFR(P<0.01). Multiple regression analysis showed that systolic blood pressure, FFA, total cholesterol, triglycerides, LDL-C, blood glucose, body mass index, eGFR were factors influencing serum uric acid independently. Multivariate binary logistic regression analysis showed that systolic blood pressure, waist circumference, total cholesterol, blood glucose, and FFA are independent risk factors to predict hyperuricemia onset while eGFR is a protective factor. Serum uric acid level is closely related to the free fatty acid, and FFA seems to be involved in the development and progression of hyperuricemia. (Chin J Endocrinol Metab, 2017, 33: 765-768) Key words: Uric acid; Free fatty acid; Risk factor

Adipose and Liver Function in Primate Offspring with Insulin Resistance Induced by Estrogen Deprivation in Utero

We recently demonstrated that offspring delivered to baboons deprived of estrogen during the second half of gestation exhibited insulin resistance. Therefore, because skeletal muscle accounts for >80% of insulin dependent glucose disposal, we suggested that estrogen in utero programs factors in fetal skeletal muscle important for insulin sensitivity in offspring. However, liver and adipose are also sites of insulin action and adipose insulin resistance can increase serum free fatty acid (FFA) levels and thereby reduce skeletal muscle insulin sensitivity. Therefore, in the current study we determined whether estrogen-deprived offspring exhibit normal adipose and hepatic function. The fasting serum levels of adiponectin, leptin, glucose, and analytes of liver function as well as the basal levels of serum FFA were similar in offspring of estrogen replete/suppressed baboons. Moreover, the normal glucose-induced decline in serum FFA levels measured in untreated offspring was also measured in offspring of letrozole-treated baboons. Fetal serum levels of adiponectin and leptin in late gestation also were similar and expression of nitrotyrosine negligible in fetal liver and adipose of untreated and letrozole-treated animals. These results indicate that offspring of letrozole-treated baboons have normal adipose and liver function and do not exhibit adipose insulin resistance. Therefore, we suggest that the insulin resistance observed in estrogen-deprived offspring primarily reflects a decline in insulin-stimulated glucose clearance by skeletal muscle and which supports our original suggestion that estrogen in utero programs factors in fetal skeletal muscle that promote insulin sensitivity in offspring.

EVALUATION OF SPIRULINA ALGAE (SPIRULINA PLATENSIS) AS A FEED SUPPLEMENT FOR JAPANESE QUAIL: NUTIRITIONAL EFFECTS ON GROWTH PERFORMANCE, EGG PRODUCTION, EGG QUALITY, BLOOD METABOLITES, SPERM-EGG PENETRATION AND FERTILITY

This study aimed to evaluate the nutritional impacts of Spirulina platensis supplementation in the feed and drinking water of the Japanese quail during the growing and laying periods. One-hundred-twenty Japanese quails (14 days old) were housed in twelve battery cages, which were randomly corresponded to three treatments: a basal mash diet (BMD) (control group), a BMD plus 1% Spirulina platensis, and a BMD plus 0.25% of Spirulina in the drinking water. The growth performance was evaluated between the 2nd and 6th week of age, then the egg production parameters and fertility rates were investigated during the following seven weeks. The Spirulina powder used in this study had 95.40% dry matter, 54.70% crude protein, 2.58% ether extract, and 1.58% crude fiber. During the growing period, the results showed that the birds provided with Spirulina powder at 1% in the feed (T1) and at 0.25% in the drinking water (T2) had higher (P<0.05) body weight (BW) and body weight gain (BWG) values than those of the control group. The total FI of T1 was higher (P<0.05) than those of the control and T2 (505.1 vs. 515.6 and 504.9 g). Besides, both of Spirulina treatments had better feed conversion ratios than that of the control group (3.3 and 3.3 versus 3.6 feed: gain). During the laying period, the Spirulina supplementation in feed or in water did not show significant (P≥0.05) effects on the egg laying rate, egg weight, daily egg mass, feed intake, feed conversion (g feed: g egg) as compared with the control group. Finally, the birds supplemented with Spirulina treatments had lesser serum cholesterol and free fatty acid levels, and displayed higher fertility values (P<0.05) than that of the control group. In conclusion, the addition of Spirulina to the feed and/ or to the drinking water of the Japanese quail had beneficial effects on growth performance and fertility, while it did not show any significant (P≥0.05) impact on the egg production, egg quality, or dressing percentage.