Serum Free Fatty Acid Levels Research Articles

Moderate quantity of lard mixed with sunflower oil attenuate lipid accumulation in mice

Lard, a fat rich in saturated fatty acids (SFAs), is regarded as a risk factor for metabolic diseases. In the present study, effect of different lard blended with sunflower oil diets on lipid accumulation in adipose tissue, liver, and serum by mouse model was researched. Body weight, body fat percentage, cross-sectional area of adipocytes, liver triglycerides (TGs), and oil red stained area in mice liver of lard blend sunflower oil (L-SFO) group were significantly lower than those of sunflower oil (SFO) group, whereas no significant differences were observed between mice of lard and L-SFO groups. Serum TG and free fatty acid levels were significantly lower in L-SFO group than in other two groups. Furthermore, data showed that sunflower oil decreased contents of hormone-sensitive lipase and carnitine palmitoyl transferase 1 (CPT-1) and increased fatty acid synthase activity in liver tissue. A mixture of lard and sunflower oil rather than only sunflower oil or lard might promote body fat loss and reduce lipid accumulation in adipose tissue, serum, and liver by promoting hydrolysis of TG, increasing β-oxidation of fatty acids. These data suggested that mixing lard and vegetable oil (e.g. sunflower oil) for cooking, or alternate using lard and vegetable oil could be beneficial for reducing body fat.

Berberine attenuates non-alcoholic steatohepatitis by regulating chemerin/CMKLR1 signalling pathway and Treg/Th17 ratio.

To observe the therapeutic effect of berberine (BBR) on non-alcoholic steatohepatitis (NASH) in rats and the underlying mechanism. A rat model of NASH was established by a high-fat diet, and BBR was used as treatment. Haematoxylin-eosin staining and Oil Red O staining were used to observe the pathological changes in the liver tissue. Western blotting and real-time PCR were used to measure the mRNA and protein levels in the liver. Flow cytometry was performed to detect the number of intrahepatic lymphocyte subtypes. The expression of pro-inflammatory cytokines in the peripheral blood was measured by ELISA. An automatic biochemical method was used to examine the level of blood lipids in the blood. Compared with the rats in the model group, the rats in the BBR group showed significantly improved liver histopathology and serum pro-inflammatory cytokines and free fatty acid (FFA) levels. Moreover, the protein and mRNA expression of chemerin, CMKLR1 and CCR2 in the liver were obviously reduced by BBR treatment. In addition, the high-fat diet remarkably reduced the intrahepatic Treg/Th17 ratio, which could be recovered by BBR treatment. Berberine can ameliorate non-alcoholic steatohepatitis, and its mechanism may be related to restoring the Treg/Th17 ratio, regulating the chemerin/CMKLR1 signalling pathway to reduce liver inflammation and reducing lipid deposition.

Role of serum periostin in severe obstructive sleep apnea with albuminuria: an observational study

BackgroundPeriostin is a matricellular protein and is a useful marker in respiratory diseases. However, the roles of periostin in patients with obstructive sleep apnea (OSA) remain unclear. Several in vitro studies have suggested that mechanical stress, hypoxia, impaired metabolism, and kidney injury, which often accompany OSA, may upregulate the expression of periostin. Meanwhile, serum periostin level has been negatively associated with body mass index (BMI) in the general population. In this study, we hypothesized that a high level of serum periostin despite being overweight/obese may discriminate severe OSA or OSA with comorbidities from mild OSA with obesity alone. We aimed to clarify the roles of periostin in patients with OSA to assist in elucidating the heterogeneity of OSA with comorbidities.MethodsAmong patients diagnosed as OSA, we examined the associations between serum periostin levels and clinical indices, including the severity of OSA, BMI, and comorbidities, using a multifaceted approach. The serum periostin levels and clinical indices were assessed after 3 months of continuous positive airway pressure (CPAP) treatment.ResultsIn 96 patients with OSA, serum periostin level was negatively correlated with BMI, albeit marginally, and tended to be higher in severe OSA than in others when adjusted for BMI. Cluster analysis identified four clusters, including two severe OSA clusters, one of which was characterized by high serum periostin levels and the presence of comorbidities, including albuminuria. In a comparative analysis of severe OSA cases (n = 53), the level of serum-free fatty acids and the frequency of albuminuria were higher in patients with high serum periostin level of ≥87 ng/mL, which was the highest quintile among all participants, than in those with low serum periostin levels (< 87 ng/mL, n = 41). In patients with severe OSA and high serum periostin levels, the levels of serum periostin and urinary albumin significantly decreased after 3 months of CPAP treatment.ConclusionsElevated serum periostin in patients with OSA despite being overweight/obese may be an indicator of severe OSA with comorbidities, particularly albuminuria.

2268-PUB: Relationship between Serum Free Fatty Acid and Proinsulin Concentrations

Background: The causes of pancreatic beta-cell dysfunction include glucose toxicity and lipotoxicity. Basic research has suggested that free fatty acids (FFAs) damage pancreatic beta-cells. However, the relationship between FFAs and pancreatic beta-cell dysfunction has not been clarified in humans. Therefore, we investigated the relationship between the serum concentrations of FFA and proinsulin (PI), a marker of pancreatic beta-cell dysfunction, in a general Japanese population. Methods: This was a cross-sectional study of 489 people (226 men, 263 women; age 35-79 years) from a rural community in Hokkaido, Japan who were not taking diabetic medication and who provided fasting blood samples. Serum PI was measured by a radioimmunoassay, and was compared among quartiles defined with respect to FFA concentration. Because the serum FFA and PI levels showed skewed distributions, univariable and multivariable regression analyses were performed after logarithmic transformation. Results: PI, age, body mass index, and fasting blood glucose and insulin were positively associated with serum FFA quartile: for PI, median (first quartile, third quartile): Q1 8.1 (6.0, 11.7), Q2 8.5 (6.9, 13.1), Q3 9.2 (6.7, 14.5), and Q4 11.2 (7.6, 16.7); p&amp;lt;0.01. Univariable regression analysis showed that ln(FFA) was positively associated with ln(PI) (partial regression coefficient: 0.19, 95% confidence interval (CI): 0.07, 0.31, p&amp;lt;0.01). This positive association remained after adjustment for age and sex (partial regression coefficient: 0.19, 95% CI: 0.07, 0.31, p&amp;lt;0.01), and also after adjustment for age, sex, and HbA1c (partial regression coefficient: 0.12, 95% CI: 0.01, 0.23, p&amp;lt;0.05). Conclusion: Serum FFA was positively associated with PI in a general Japanese population. Thus, FFA may play a role in pancreatic beta-cell dysfunction. Disclosure K. Chiba: None. A. Nakamura: None. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., MDS CO. LTD., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd. S. Ukawa: None. K. Nakamura: None. T. Nakagawa: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk A/S, Sanofi. Consultant; Self; Astellas Pharma Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Medscape, Medtronic, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. A. Tamakoshi: None. T. Atsumi: Consultant; Self; Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline plc., Pfizer Inc., UCB Japan Co. Ltd. Speaker’s Bureau; Self; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB Japan Co. Ltd.

SUN-603 Electronic Cigarette Exposure Induces Pro-Inflammatory Changes in Adipose Tissue in Apolipoprotein E (APOE) Knockout Mice

Electronic nicotine delivery systems or electronic cigarettes (e-cigarettes) are becoming exceptionally popular in the world as an alternative to conventional nicotine cigarettes, both in smokers and people who have never smoked. Nicotine can induce lipolysis in adipose tissue, leading to increased serum free fatty acids (FFA). Increased levels of FFA are one of the key elements in inducing a pro-inflammatory response and lead to ectopic lipid accumulation, lipotoxicity, mitochondrial dysfunction and metabolic disease. Our laboratory has shown that chronic e-cigarette exposure induces cardiac dysfunction, atherosclerosis and hepatic steatosis in the ApoE knockout (KO) model associated with increased levels of serum FFA. In this study, we investigated the role of adipose tissue in the metabolic changes associated with e-cigarette exposure. ApoE KO mice were exposed to saline, e-cigarette without nicotine [e-cigarette (0%)] and e-cigarette with 2.4% nicotine [e-cigarette (2.4%)] aerosol for 12 weeks. Western blot analyses from adipose tissue showed that mice treated with e-cigarette (2.4%) had decrease levels of SIRT1 when compared to mice treated with saline or e-cigarette (0%). Transcriptomic analysis of the differentially expressed genes shows a differential transcriptional response to e-cigarette (2.4%) in adipose tissue in comparison with e-cigarette (0%) or saline. The RNA-seq examination using ingenuity pathway analysis (IPA) software, revealed dysregulation of fibrosis, agranulocyte and granulocyte adhesion and diapedesis pathways in e-cigarette (2.4%) -exposed adipose tissue. Overall, we found an inflammatory phenotype associated with decreased levels of SIRT1 in adipose tissue of mice treated with e-cigarette (2.4%). Understanding the consequences of e-cigarette use on metabolic disease is directly relevant to the development of policies related to e-cigarette use.

Shenmai Injection Improves Energy Metabolism in Patients With Heart Failure: A Randomized Controlled Trial.

BackgroundIn recent years, the application of Shenmai (SM) injection, a traditional Chinese medicine (TCM), to treat heart failure (HF) has been gradually accepted in China. However, whether SM improves energy metabolism in patients with HF has not been determined due to the lack of high-quality studies. We aimed to investigate the influence of SM on energy metabolism in patients with HF.MethodsThis single-blind, controlled study randomly assigned 120 eligible patients equally into three groups receiving SM, trimetazidine (TMZ), or control in addition to standard medical treatment for HF for 7 days. The primary endpoints were changes in free fatty acids (FFAs), glucose, lactic acid (LA), pyroracemic acid (pyruvate, PA) and branched chain amino acids (BCAAs) in serum. The secondary outcomes included the New York Heart Association (NYHA) functional classification, TCM syndrome score (TCM-s), left ventricular injection fraction (LVEF), left ventricular internal diastolic diameter (LVIDd), left ventricular internal dimension systole (LVIDs), and B-type natriuretic peptide (BNP).ResultsAfter treatment for 1 week, the NYHA functional classification, TCM-s, and BNP level gradually decreased in the patients in all three groups, but these metrics were significantly increased in the patients in the SM group compared with those in the patients in the TMZ and control groups (P < 0.05). Moreover, energy metabolism was improved in the NYHA III–IV patients in the SM group compared with those in the patients in the TMZ and control groups as evidenced by changes in the serum levels of FFA, LA, PA, and BCAA.ConclusionsIntegrative treatment with SM in addition to standard medical treatment for HF was associated with improved cardiac function compared to standard medical treatment alone. The benefit of SM in HF may be related to an improvement in energy metabolism, which seems to be more remarkable than that following treatment with TMZ.

Effects of maternal vitamin D3 during pregnancy on FASN and LIPE mRNA expression in offspring pigs

AbstractIn this study, sows were fed 200 (LD), 800 (ND) and 3200 (HD) IU of vitamin D3/kg basal diet during pregnancy (from 41 d to birth), respectively. All their offspring pigs were fed the same vitamin D3 replete die. At 150 days of age, a total of 18 offspring pigs (six offspring pigs per maternal diet group, sex balance) were weighed and slaughtered to investigate effects of maternal vitamin D3 during pregnancy on fatty acids synthase (FASN) and hormone-sensitive lipase (LIPE) expression in offspring pigs. The results showed that LD offspring pigs had higher FASN mRNA expression and the ratio of FASN/LIPE mRNA expression in subcutaneous adipose tissue, as well as higher LIPE mRNA expression of longissimus dorsal muscle, whereas, had lower the ratio of FASN/LIPE mRNA expression in longissimus dorsal muscle compared with ND or HD offspring pigs, respectively. Meanwhile, LD offspring pigs had higher carcass fat, average backfat thickness (ABFT), serum insulin and leptin levels, lower intramuscular fat (IMF), serum free fatty acid and triglycerol levels compared with ND or HD offspring pigs. In addition, the ratio of FASN/LIPE mRNA expression was negatively correlated with IMF content, and positively correlated to carcass fat content and ABFT in offspring pigs. Meanwhile, FASN mRNA expression was positively correlated with carcass fat content, while negatively correlated with ABFT in offspring pigs. These results suggested that maternal vitamin D3 affected fat accumulation and meat quality by regulating FASN and LIPE mRNA expression in offspring pigs.

Growth hormone upregulates ANGPTL4 mRNA and suppresses lipoprotein lipase via fatty acids: Randomized experiments in human individuals

ObjectivesLipoprotein lipase (LPL) catalyzes the hydrolysis of circulating triglycerides into free fatty acids (FFA) and thereby promotes FFA uptake in peripheral tissues. LPL is negatively regulated by angiopoietin-like protein 4 (ANGPTL4) presumably by an FFA-dependent mechanism. Growth hormone (GH) suppresses LPL activity, but it is unknown whether this is mediated by FFA and ANGPTL4. Therefore, we investigated the concerted effect of GH on ANGPTL4 and LPL in the presence and absence of lipolysis in two in vivo studies in human subjects. MethodsIn a randomized, placebo-controlled, cross-over study, nine obese men were examined after injection of 1) a GH bolus, and 2) a GH-receptor antagonist followed by four adipose tissue biopsies obtained over a 5-h period. In a second study, nine hypopituitary men were examined in a 2 × 2 factorial design including GH and acipimox (an anti-lipolytic agent), with biopsies from adipose tissue and skeletal muscle obtained during a basal period and a subsequent hyperinsulinemic-euglycemic clamp. The mRNA expression of ANGPTL4 and LPL as well as LPL activity were analyzed in the biopsies. ResultsIn both studies, GH increased serum FFA levels, upregulated ANGPTL4 mRNA expression and suppressed LPL activity. In study 2, acipimox completely suppressed FFA levels and antagonized the effects of GH on ANGPTL4 and LPL. ConclusionsThese human in vivo studies demonstrate that GH upregulates ANGPTL4 mRNA and suppresses LPL activity via an FFA-dependent mechanism.

Anti-depressive effects of Kai-Xin-San on lipid metabolism in depressed patients and CUMS rats using metabolomic analysis

Ethnopharmacological relevanceIn this study, in order to explore potential depressive biomarkers and potential regulatory targets of KXS on depression, we assessed the effects of Kai-Xin-San (KXS) on lipid metabolism in depressed patients (DPs) and rats exposed to chronic and unpredictable mild stress (CUMS). Materials and methodsSerum samples were collected from DPs, DPs with 8 weeks of KXS treatment (KXS) and healthy controls (HCs), and non-targeted lipidomics was used to analyze the effect of KXS on serum lipid metabolites in DPs. Based on UPLC-Q-TOF/MS technology, differential metabolites were validated in a large sample size. The potential regulatory network of KXS was analyzed by bioinformatic analysis, and the expressions of proteins in serum were verified using western boltting analysis. Moreover, effects of KXS on serum lipid and lipid metabolism-related hormone levels in CUMS rats were detected by enzyme-linked immunosorbent assay and enzymatic method. ResultsWe validated that the levels of six serum lipid metabolites (N-Desmethylcitalopram (HMDB14021), PC(14:1(9Z)/24:0) (HMDB07926), PC(P-18:1(11Z)/20:0) (HMDB11281), PC(O-18:0/20:4(8Z,11Z,14Z,17Z)) (HMDB13420), PC(16:0/P-18:0) (HMDB07995) and PC(16:0/P-18:1(11Z)) (HMDB07996)) between HC/DP groups and between DP/KXS groups were significantly different. Among these six metabolites, HMDB07995, HMDB07996, HMDB13420 and HMDB11281 were highly sensitive and specific for depression and KXS treatment by receiver operating characteristic (ROC) curve analysis. matrix metalloproteinases (MMPs) including MMP2 and MMP9, apolipoproteins (Apo) including APOA1 and APOC1 were up-regulated and apolipoproteins (Apo) including APOB, APOD and APOE, phospholipid transfer protein (PLTP), Paraoxonase 1 (PON1) were down-regulated in DPs, and KXS treatment could reverse these changes. In CUMS rats, KXS could increase the open-field score, sucrose preference and body weight, and reduce immobility time. Furthermore, KXS increased the serum levels of the above-mentioned six metabolites, reduced serum total cholesterol (TCH), triglyceride (TG) and free fatty acid (FFA) levels and increased the serum high-density lipoprotein cholesterol (HDL-C) level in CUMS rats. In addition, leptin and ghrelin were down-regulated by KXS. ConclusionsThe results suggested that KXS exerted antidepressant effects by regulating the signaling pathways involved in lipid metabolism disorders. The lipid metabolites might be potential biomarkers of depression and possible targets for KXS-based treatment of depression.

L-Carnitine Is Involved in Hyperbaric Oxygen-Mediated Therapeutic Effects in High Fat Diet-Induced Lipid Metabolism Dysfunction.

Lipid metabolism dysfunction and obesity are serious health issues to human beings. The current study investigated the effects of hyperbaric oxygen (HBO) against high fat diet (HFD)-induced lipid metabolism dysfunction and the roles of L-carnitine. C57/B6 mice were fed with HFD or normal chew diet, with or without HBO treatment. Histopathological methods were used to assess the adipose tissues, serum free fatty acid (FFA) levels were assessed with enzymatic methods, and the endogenous circulation and skeletal muscle L-carnitine levels were assessed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, western blotting was used to assess the expression levels of PPARα, CPT1b, pHSL/HSL, and UCP1. HFD treatment increased body/adipose tissue weight, serum FFA levels, circulation L-carnitines and decreased skeletal muscle L-carnitine levels, while HBO treatment alleviated such changes. Moreover, HFD treatment increased fatty acid deposition in adipose tissues and decreased the expression of HSL, while HBO treatment alleviated such changes. Additionally, HFD treatment decreased the expression levels of PPARα and increased those of CPT1b in skeletal muscle, while HBO treatment effectively reverted such changes as well. In brown adipose tissues, HFD increased the expression of UCP1 and the phosphorylation of HSL, which was abolished by HBO treatment as well. In summary, HBO treatment may alleviate HFD-induced fatty acid metabolism dysfunction in C57/B6 mice, which seems to be associated with circulation and skeletal muscle L-carnitine levels and PPARα expression.

Structural characteristic of a sulfated polysaccharide from Gracilaria Lemaneiformis and its lipid metabolism regulation effect.

A sulfated polysaccharide extracted from Gracilaria lemaneiformis (GLP) with a prominent effect in regulating lipid metabolism was isolated. The molecular weight was 31.5 kDa and it was composed mainly of galactose, glucose and xylose. Fourier-transform infrared (FT-IR) spectrum and nuclear magnetic resonance (NMR) analysis suggested that GLP was composed of the following repeating unit: [3-β-Gal-4(OSO3)-1→4-α-3,6-anhydrogal-2(OSO3)-1→]. GLP could significantly decrease serum total cholesterol, triglyceride and free fatty acid levels and lower alanine aminotransferase and aspartate aminotransferase activities in high-fat-diet mice. Additionally, GLP could keep the body weight and attenuate accumulation of fat surrounding the liver and epididymis induced by high-fat diet. Results of RT-PCR indicated that GLP might regulate lipid metabolism and accelerate free fatty acid oxidation by up-regulating the expression of the PPARα, ACS and CPT1a gene. The present study suggests that GLP may be potentially useful for regulating lipid metabolism.

Standardized rice bran extract improves hepatic steatosis in HepG2 cells and ovariectomized rats.

BACKGROUD/OBJECTIVESHepatic steatosis is the most common liver disorder, particularly in postmenopausal women. This study investigated the protective effects of standardized rice bran extract (RBS) on ovariectomized (OVX)-induced hepatic steatosis in rats.MATERIALS/METHODSHepG2 cells were incubated with 200 µM oleic acid to induce lipid accumulation with or without RBS and γ-oryzanol. OVX rats were separated into three groups and fed a normal diet (ND) or the ND containing 17β-estradiol (E2; 10 µg/kg) and RBS (500 mg/kg) for 16 weeks.RESULTSRBS supplementation improved serum triglyceride and free fatty acid levels in OVX rats. Histological analysis showed that RBS significantly attenuated hepatic fat accumulation and decreased hepatic lipid, total cholesterol, and triglyceride levels. Additionally, RBS suppressed the estrogen deficiency-induced upregulation of lipogenic genes, such as sterol regulatory element-binding protein 1 (SREBP1), acetyl-CoA carboxylase 1, fatty acid synthase, glycerol-3-phosphate acyltransferase, and stearoyl-CoA desaturase 1.CONCLUSIONSRBS and γ-oryzanol effectively reduced lipid accumulation in a HepG2 cell hepatic steatosis model. RBS improves OVX-induced hepatic steatosis by regulating the SREBP1-mediated activation of lipogenic genes, suggesting the benefits of RBS in preventing fatty liver in postmenopausal women.

Pathogenetic aspects of the effects of the bacterial overgrowth syndrome on metabolism of free fatty acids in patients with chronic diffusive liver diseases

Objective — to investigate blood serum levels of free fatty acids of patients with chronic diffusive liver diseases (CDLD) depending on the etiology and microbiocenosis disturbances.Materials and methods. The study involved 98 patients with CDLD aged 59.2 ± 2.4 years. Depending on the etiological factors of liver injury, they were divided into five groups: group I consisted of 14 patients with non‑alcoholic fatty liver disease (NAFLD); group II — 31 patients with non‑alcoholic steatohepatitis (NASH); III — 12 persons with chronic viral hepatitis associated with C virus (CHC); IV — 24 patients with alcoholic liver disease (ALD); V — 17 patients with toxic hepatitis (TH). The control group included 16 practically healthy subjects. The diagnosis of bacterial overgrowth syndrome (BOS) was based on the glucose breath test results with the use of «Gastro» Gastrolyzer (Bedfont Scientific Ltd, UK). Blood serum levels of free fatty acids (FFAs) and their fractions were measured with gas chromatography.Results. The mean level of exhaled hydrogen in all groups was higher than normal, thus confirming the BOS in patients with CDLD. Thus index was significantly higher in patients with ALD (10.9 ± 1.6 ppm) and TH (13.1 ± 2.8 ppm) in comparison with subjects with NAFLD (6.6 ± 1.0 ppm; р &lt; 0.05). The FFA spectrum in blood serum revealed multidirectional changes depending on the etiological factor. The significant increase of FFA levels vs control groups has been established in patients with NAFLD, NASH and ALD, and patients with CHC and TH demonstrated a tendency to its reduction when compared with the control group.Conclusions. The changes in the small intestine microflora was observed in 64.3 % of CDLD patients, predominantly at alcoholic liver disease (79.2 %), and more are at NAFLD (57.1 %). The serum FFA levels were increased in patients with NAFLD, NASH and ALD at both BOS presence and absence, the most intensive it was at SOP absence.

Daisaikoto Prevents Post-dieting Weight Regain by Reversing Dysbiosis and Reducing Serum Corticosterone in Mice.

Weight loss is often temporary and is generally followed by recurrent weight gain and a relapse of metabolic complications, whose severity may be even greater upon recurrence. Preventing recurrent obesity, understanding the control of the energy balance subsequent to weight loss, and reversing the predisposition to obesity are critical factors that warrant an in-depth study. Several Kampo medicines, including daisaikoto, have traditionally been used to manage obesity, but their mechanisms of action are not well studied and their effects on weight regain are unknown. Here, we investigated the therapeutic potential and mechanism of action of daisaikoto in a mouse model of recurrent obesity. The mouse model was established by feeding mice a high-fat diet, followed by a normal chow, and a second course of the high-fat diet. Daisaikoto inhibited not only obesity and regaining of weight post-dieting, but also dysbiosis, thereby overcoming the predisposition to obesity. Furthermore, we found that recurrent obesity or long-term consumption of the high-fat diet elevated serum glucose, insulin, and corticosterone levels, and that daisaikoto lowered serum cholesterol and free fatty acid levels. These results are consistent with the hypothesis that this medication may inhibit lipid absorption by inhibiting pancreatic lipase. However, daisaikoto had no effect on the body weight of lean mice fed a normal chow, suggesting that although this medicine prevents lipid absorption, it does not cause excessive weight loss. In conclusion, our results elucidate the mechanisms underlying daisaikoto activity, and suggest that it may serve as a safe and effective anti-obesity drug.

Evidence in obese children: contribution of tri-ponderal mass index or body mass index to dyslipidemia, obesity-inflammation, and insulin sensitivity.

Background Chronic inflammation plays a critical role in the development of obesity-related metabolic dysfunction. The tri-ponderal mass index (TMI) may be more effective than body mass index (BMI) for estimating body fat levels. This study compared the efficacy of BMI and TMI in screening for dyslipidemia, insulin sensitivity, and inflammation in childhood obesity. Methods This study included 80 children who were classified as normal weight, overweight or obese using standardized BMI (BMI standard deviation score [SDS]) and TMI measurements. Fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), triglycerides, total cholesterol, liver function enzymes, leptin, serum free fatty acid (FFA), fetuin-A, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6 levels were evaluated using both classification systems. Results LDL-C levels significantly differed within the groups by BMI, and serum FFA levels differed only according to the TMI. Serum MCP-1, TNF-α, IL-6, and fetuin-A levels showed no difference according to the TMI or BMI SDS. Fetuin-A levels did not differ between the insulin-resistant and non-resistant cases. Fetuin-A was the only inflammatory marker positively correlated with BMI. No inflammatory markers correlated with TMI. Fetuin-A, MCP-1, TNF-α, and IL-6 correlated with each other, but not with metabolic parameters. Conclusions BMI SDS and TMI were associated with metabolic disturbances in childhood obesity. Weight versus heightn values may be related more to metabolic parameters than to inflammatory changes.

PSIV-B-34 Late-Breaking: Targeted metabolomics analysis reveals that dietary super-nutritional selenium regulates energy metabolism homeostasis in pig liver

Abstract Energy metabolism is a major mechanism of power reduction needed to maintain the redox state in an organism. By using a selenium (Se)-deficiency model we have previously demonstrated that Se can shift glycolysis by regulating the redox state in pig skeletal muscle. How dietary super-nutritional Se affects the energy metabolism in pig liver remains unknown. In the present study, super-nutritional Se supplementation (as selenomethionine) effects on liver selenoprotein expression and energy metabolite profiles in pigs were evaluated. In total, 36 castrated male pigs (Duroc × Landrace × Yorkshire, 62.3 ± 3.3 kg) were randomly assigned to two treatment groups with six replicates of three pigs per replicate. The two treatment groups received the same basal diet supplemented with different levels of selenomethionine: Se adequate (Se-A, 0.25 mg Se/kg) and Se supra-nutritional (2.5 mg Se/kg) for 60 days. Animals were then scarified and their livers were sampled for Se content, selenotranscriptome, and energy-targeted metabolite profile analysis. Super-nutritional Se supplementation increased the levels of serum fasting glucose, insulin, and free fatty acid levels (P &amp;lt; 0.05), as well as elevated the total Se liver content (P &amp;lt; 0.05). Glutathione peroxidase 4 mRNA expression was upregulated, while thioredoxin reductase 1 and selenoprotein W mRNA expression levels were downregulated in the super-nutritional Se group. LC-MS-based target metabolomics showed that high Se supplementation increased the levels of most metabolites involved in glycolysis, pentose phosphate pathway, tricarboxylic acid cycle, and acylcarnitine metabolism. These results indicated that dietary super-nutritional Se can regulate energy metabolism homeostasis in the pig liver.

A high serum-free fatty acid level is associated with cancer

PurposeThe objectives of this work were to investigate whether the serum-free fatty acid (FFA) level is meaningful in cancer patients and its role in cancer diagnosis.MethodsA total of 2206 patients were divided into a cancer group (n = 1019) and a noncancer group (n = 1187). Age, sex, body mass index (BMI), and serum FFA and serum albumin levels were collected. Cancer patients were divided into subgroups according to the location of the cancer. We then compared serum FFA levels among the tumor subgroups. A receiver operating characteristic (ROC) curve analysis was performed to further evaluate the diagnostic ability of the FFA level. SPSS 22.0 software was used to analyze the results.ResultsThe FFA level was higher in the cancer group than in the noncancer group. According to the multivariate analysis, there was also an increased risk of cancer associated with a high FFA level after adjusting for old age, female sex, and a low BMI. In the subgroup analysis, the FFA level in patients with lung cancer, gastric cancer, thyroid cancer, rectal cancer, colon cancer, and ovarian cancer was significantly higher than that in noncancer patients. The area under the effect–time curve (AUC) of FFAs in the whole cancer group was 0.58, while the thyroid cancer, rectal cancer, and ovarian cancer subgroups had AUCs > 0.6.ConclusionOur study provides clinical evidence to support that fatty acid metabolism is associated with cancers and demonstrates that a high FFA level in the serum may be an indicator of cancer.

Sesamol intervention ameliorates obesity-associated metabolic disorders by regulating hepatic lipid metabolism in high-fat diet-induced obese mice.

BackgroundObesity has currently become a serious social problem to be solved. Sesamol, a natural bioactive substance extracted from sesame oil, has shown multiple physiological functions, and it might have an effect on the treatment of obesity.ObjectiveThis study was conducted to investigate the therapeutic effect and potential mechanisms of sesamol on the treatment of obesity and metabolic disorders in high-fat diet (HFD)-induced obese mice.MethodsC57BL/6J male mice were fed HFD for 8 weeks to induce obesity, followed by supplementation with sesamol (100 mg/kg body weight [b.w.]/day [d] by gavage) for another 4 weeks. Hematoxylin and eosin staining was used to observe lipid accumulation in adipose tissues and liver. Chemistry reagent kits were used to measure serum lipids, hepatic lipids, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. ELISA kits were used to determine the serum insulin and free fatty acid (FFA) levels. Western blotting was used to detect the protein levels involved in lipid metabolism in the liver.ResultsSesamol significantly reduced the body weight gain of obese mice and suppressed lipid accumulation in adipose tissue and liver. Sesamol also improved serum and hepatic lipid profiles, and increased insulin sensitivity. In the sesamol-treated group, the levels of serum ALT and AST decreased significantly. Furthermore, after sesamol treatment, the hepatic sterol regulatory element binding protein-1 (SREBP-1c) decreased, while the phosphorylated hormone sensitive lipase (p-HSL), the carnitine palmitoyltransferase 1α (CPT1α), and the peroxisome proliferator-activated receptor coactivator-1α (PGC1α) increased, which were responsible for the fatty acid synthesis, lipolysis, and fatty acid β-oxidation, respectively.ConclusionsSesamol had a positive effect on anti-obesity and ameliorated the metabolic disorders of obese mice. The possible mechanism of sesamol might be the regulation of lipid metabolism in the liver.

Characterization of the duration of treatment with diazoxide in infants with prolonged hyperinsulinism (PHI).

Background Prolonged neonatal hyperinsulinism (PHI) causes hypoglycemia in the neonatal period and is associated with perinatal stress. Even though diazoxide is an effective treatment option for PHI, it has serious adverse effects making an argument for safe yet expeditious wean off of diazoxide while ensuring normoglycemia. The objective of this study was to characterize clinical course, dose requirement and duration of treatment with diazoxide in our cohort of infants diagnosed with PHI. Methods A retrospective chart review of infants diagnosed with PHI during a 6-year period was done documenting the diagnostic workup and the duration of treatment with diazoxide. Results PHI was diagnosed (n = 20; mean ± standard deviation [SD]) at 14.3 ± 22.4 days. Elevated insulin (8.3 ± 8.4 mIU/L), normal cortisol (15.5 ± 6.6 μg/dL [6-21]), normal growth hormone (18.8 ± 15.7 ng/mL [0.1-6.2]) and inappropriate low serum free fatty acids (0.3 ± 0.2 mmol/L [>1.5]) levels were measured during hypoglycemia (plasma glucose <50 mg/dL). Detectable insulin at the time of hypoglycemia was measured in 17 of 20 infants while the same number (17/20) of infants had a positive glucagon stimulation test (GST). The dose of diazoxide was 10 ± 3.7 mg/kg/day and duration of treatment was 44.9 ± 27.9 days. Conclusions This study illustrates that the duration of treatment with diazoxide in infants with PHI can be shorter than previously reported in the literature. We speculate that active tapering of diazoxide started within a week after discharge from hospital as well an outpatient tapering of diazoxide based on glucose monitoring were possible reasons for this outcome.

Effect of Chinese Herbal Monomer Hairy Calycosin on Nonalcoholic Fatty Liver Rats and its Mechanism

Chinese herbal monomer hairy Calycosin is a flavonoid extracted from Radix astragali. The aim of the research was to investigate the effect and mechanism of Hairy Calycosin on Non-Alcoholic Fatty Liver Dieases (NAFLD) in rats. 60 rats were randomly divided into 6 groups, then NAFLD rat models were prepared and treated with different doses of Hairy Calycosin (0.5, 1.0, 2.0 mg/kg) or Kathyle relatively. Both 1.0 mg/kg and 2.0 mg/kg Hairy Calycosin treatment could significantly increase the serum Superoxide Dismutase (SOD) content of the model rats and reduce the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Free Fatty Acid (FFA), IL-6, tumor necrosis factor-alpha (TNF-α) and liver homogenate malondialdehyde (MDA), while 2.0 mg/kg Hairy Calycosin can down-regulate liver tissue cytochrome p450 2E1 (CYP2E1). In the electron microscope, compared with the model control group, the mitochondrial swelling in the hepatocytes of Hairy Calycosin (1.0, 2.0 mg/kg) treatment group was significantly reduced, the ridge on the inner membrane of mitochondria increased, and the lipid droplets became much smaller. Hairy Calycosin can effectively control the lipid peroxidation in liver tissues of rats with NAFLD, and reduce the levels of serum TNF-α, IL-6, MDA and FFA, effectively improve the steatosis and inflammation of liver tissue, and down-regulate the expression of CYP2E1, inhibit apoptosis of hepatocytes.