Camellia oil has become an important plant oil in China in recent years, but its effects on non-alcoholic fatty liver disease (NAFLD) have not been documented. In this study, the effects of camellia oil, soybean oil, and olive oil on NAFLD were evaluated by analyzing the fatty acid profiles of the plant oils, the serum lipids and lipoproteins of rats fed different oils, and by cytological and ultrastructural observation of the rats' hepatocytes. Analysis of fatty acid profiles showed that the polyunsaturated fatty acid (PUFA) n-6/n-3 ratio was 33.33 in camellia oil, 12.50 in olive oil, and 7.69 in soybean oil. Analyses of serum lipids and lipoproteins of rats showed that the levels of total cholesterol and low-density lipoprotein cholesterol in a camellia oil-fed group (COFG) were lower than those in an olive oil-fed group (OOFG) and higher than those in a soybean oil-fed group (SOFG). However, only the difference in total cholesterol between the COFG and SOFG was statistically significant. Cytological observation showed that the degree of lipid droplet (LD) accumulation in the hepatocytes in the COFG was lower than that in the OOFG, but higher than that in the SOFG. Ultrastructural analysis revealed that the size and number of the LDs in the hepatocytes of rats fed each of the three types of oil were related to the degree of damage to organelles, including the positions of nuclei and the integrity of mitochondria and endoplasmic reticulum. The results revealed that the effect of camellia oil on NAFLD in rats was greater than that of soybean oil, but less than that of olive oil. Although the overall trend was that among the three oil diets, those with a lower n-6/n-3 ratio were associated with a lower risk of NAFLD, and the effect of camellia oil on NAFLD was not entirely related to the n-6/n-3 ratio and may have involved other factors. This provides new insights into the effect of oil diets on NAFLD.
Animals ; Camellia/chemistry* ; Fatty Acids/analysis* ; Hepatocytes/ultrastructure* ; Lipid Droplets/physiology* ; Lipids/blood* ; Male ; Non-alcoholic Fatty Liver Disease/pathology* ; Plant Oils/administration & dosage* ; Rats ; Rats, Sprague-Dawley

Type 2 diabetes mellitus (T2DM) is recognized as one of the most prevalent metabolic diseases, and it is mostly associated with oxidative stress, atherosclerosis and dyslipidemia. Paraoxonase 2 (PON2) due to its antioxidant properties may play a role in the atherosclerosis development. Although long-chain omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) have been shown to reduce the risk of cardiovascular disease, the exact mechanism of action is still unknown. Our goal in this study was to determine the effect of EPA administration on gene expression of PON2 in patients with T2DM. Present study was a randomized, controlled double-blind trial. Thirty-six patients with T2DM were randomly allocated to receive 2 g/day EPA (n = 18) or placebo (n = 18) for 8 weeks. There were no significant differences between 2 groups concerning demographic or biochemical variables, and dietary intakes as well (p > 0.05). However, patients received EPA showed a significant increase in the gene expression of PON2 compared with placebo group (p = 0.027). In addition, high-density lipoprotein cholesterol increased and fasting blood sugar decreased significantly after EPA supplementation compared with control group. Taken together, supplementation with 2 g/day EPA could be atheroprotective via the upregulation of PON2 in patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03258840
Aryldialkylphosphatase* ; Atherosclerosis ; Blood Glucose ; Cardiovascular Diseases ; Cholesterol ; Diabetes Mellitus, Type 2* ; Dyslipidemias ; Eicosapentaenoic Acid* ; Fasting ; Fatty Acids, Unsaturated ; Gene Expression* ; Humans ; Lipoproteins ; Metabolic Diseases ; Oxidative Stress ; Up-Regulation

Free fatty acid (FFA) intake regulates blood pressure and vascular reactivity but its direct effect on contractility of systemic arteries is not well understood. We investigated the effects of saturated fatty acid (SFA, palmitic acid), polyunsaturated fatty acid (PUFA, linoleic acid), and monounsaturated fatty acid (MUFA, oleic acid) on the contractility of isolated mesenteric (MA) and deep femoral arteries (DFA) of Sprague–Dawley rats. Isolated MA and DFA were mounted on a dual wire myograph and phenylephrine (PhE, 1–10 µM) concentration-dependent contraction was obtained with or without FFAs. Incubation with 100 µM of palmitic acid significantly increased PhE-induced contraction in both arteries. In MA, treatment with 100 µM of linoleic acid decreased 1 µM PhE-induced contraction while increasing the response to higher PhE concentrations. In DFA, linoleic acid slightly decreased PhE-induced contraction while 200 µM oleic acid significantly decreased it. In MA, oleic acid reduced contraction at low PhE concentration (1 and 2 µM) while increasing it at 10 µM PhE. Perplexingly, depolarization by 40 mM KCl-induced contraction of MA was commonly enhanced by the three fatty acids. The 40 mM KCl-contraction of DFA was also augmented by linoleic and oleic acids while not affected by palmitic acid. SFA persistently increased alpha-adrenergic contraction of systemic arteries whereas PUFA and MUFA attenuated PhE-induced contraction of skeletal arteries. PUFA and MUFA concentration-dependent dual effects on MA suggest differential mechanisms depending on the types of arteries. Further studies are needed to elucidate underlying mechanisms of the various effects of FFA on systemic arteries.
Animals ; Arteries ; Blood Pressure ; Fatty Acids ; Fatty Acids, Unsaturated ; Femoral Artery ; Linoleic Acid ; Mesenteric Arteries ; Oleic Acid ; Oleic Acids ; Palmitic Acid ; Phenylephrine ; Rats ; Receptors, Adrenergic, alpha ; Vasoconstriction

BACKGROUND: Chronic inflammation has been linked to insulin resistance and type 2 diabetes mellitus (T2DM). High-fat diet (HFD)-derived fatty acid is associated with the activation of chronic inflammation in T2DM. PF-04620110, which is currently in phase 1 clinical trials as a selective acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) inhibitor, is a potent anti-diabetic agent that may be important for the regulation of chronic inflammation in T2DM. However, the mechanisms by which PF-04620110 regulates fatty acid-induced chronic inflammation remain unclear. METHODS: PF-04620110 was used in vitro and in vivo. DGAT1-targeting gRNAs were used for deletion of mouse DGAT1 via CRISPR ribonucleoprotein (RNP) system. The activation of NLRP3 inflammasome was measured by immunoblot or cytokine analysis in vitro and in vivo. RESULTS: Here we show that PF-04620110 suppressed fatty acid-induced nucleotide-binding domain, leucine-rich-repeat-containing receptor (NLR), pyrin-domain-containing 3 (NLRP3) inflammasome activation in macrophages. In contrast, PF-04620110 did not change the activation of the NLR family, CARD-domain-containing 4 (NLRC4), or the absent in melanoma 2 (AIM2) inflammasomes. Moreover, PF-04620110 inhibited K⁺ efflux and the NLRP3 inflammasome complex formation, which are required for NLRP3 inflammasome activation. PF-04620110 reduced the production of interleukin 1β (IL-1β) and IL-18 and blood glucose levels in the plasma of mice fed HFD. Furthermore, genetic inhibition of DGAT1 suppressed fatty acid-induced NLRP3 inflammasome activation. CONCLUSION: Our results suggest that PF-04620110 suppresses fatty acid-induced NLRP3 inflammasome activation.
Animals ; Blood Glucose ; Clinical Trials, Phase I as Topic ; Clustered Regularly Interspaced Short Palindromic Repeats ; Diabetes Mellitus, Type 2 ; Diacylglycerol O-Acyltransferase ; Diet, High-Fat ; Fatty Acids ; Humans ; In Vitro Techniques ; Inflammasomes ; Inflammation ; Insulin Resistance ; Interleukin-18 ; Interleukins ; Macrophages ; Melanoma ; Mice ; Plasma ; Ribonucleoproteins ; RNA, Guide

BACKGROUND/OBJECTIVES: The effects of fish consumption by subjects with prediabetes on the metabolic risk factors were examined based on the data from the 6th Korea National Health and Nutrition Examination Surveys in 2015. SUBJECTS/METHODS: A total of 1,520 subjects who agreed to participate in a blood test and dietary intake survey were divided into a prediabetes group and normal blood glucose group, and the level of the subjects' fish consumption was divided into ≤ 17.0 g/day, 18.0–93.0 g/day, and ≥ 94 g/day. The correlation between the level of fish intake and the metabolic risk factors was evaluated by multinomial logistic regression analysis. RESULTS: A significant difference in the gender distribution was observed in the prediabetes group, which is a group with a high risk of non-communicable diseases, according to the fish intake, and there were significant differences in the total energy intake, protein intake, n-3 fatty acids intake, and the intakes of sodium and micro-nutrients according to the intake group (P < 0.05). In addition, the blood total cholesterol (TC) decreased 0.422 fold in model 1 (unadjusted) [95% confidence interval (CI): 0.211–0.845] and 0.422 fold in model 2 (adjusted for sex) (95% CI: 0.210–0.846) in those with a fish intake of 18.0–93.0 g/day (P < 0.05) compared to those with a fish intake of ≤ 17.0 g/day. The blood TC decreased 0.555 fold (95% CI: 0.311–0.989) in model 1 and 0.549 fold (95% CI: 0.302–0.997) in model 2 in those with a fish intake of ≥ 94 g/day compared to those with a fish intake of ≤ 17.0 g/day (P < 0.05). CONCLUSIONS: Subjects with prediabetes or the metabolic risk factors can maintain their blood low density lipoprotein cholesterol (LDL-C) and blood TC concentrations at the optimal level by consuming fish (18.0–93.0 g/day).
Blood Glucose ; Cholesterol ; Cholesterol, LDL ; Eating ; Energy Intake ; Fatty Acids, Omega-3 ; Hematologic Tests ; Korea* ; Logistic Models ; Noncommunicable Diseases ; Nutrition Surveys ; Prediabetic State* ; Risk Factors* ; Sodium

Various endocrine dysfunctions occur during chemotherapy, including hypoglycemia. However, reports of hypoglycemia associated with 6-mercaptopurine (6-MP) are rare. Herein, we report an 8-year-old boy with severe symptomatic hypoglycemia likely due to 6-MP during chemotherapy. He had been diagnosed with acute lymphoblastic leukemia 3 years previously and was in the maintenance chemotherapy period. Treatment included oral dexamethasone, methotrexate, and 6-MP, of which only 6-MP was administered daily. Hypoglycemic symptoms appeared mainly at dawn, and his serum glucose dropped to a minimum of 37 mg/dL. Laboratory findings showed nothing specific other than increased serum cortisol, free fatty acids, ketone, alanine aminotransferase, and aspartate aminotransferase. Under the hypothesis of hypoglycemia due to chemotherapy drugs, we changed the time of 6-MP from evening to morning and recommended him to ingest carbohydrate-rich foods before bedtime. Hypoglycemia improved dramatically, and there was no further episode during the remaining maintenance chemotherapy period. To the best of our knowledge, this is the first report of this type of hypoglycemia occurring in an Asian child including Korean.
6-Mercaptopurine* ; Alanine Transaminase ; Asian Continental Ancestry Group ; Aspartate Aminotransferases ; Blood Glucose ; Child* ; Dexamethasone ; Drug Therapy* ; Fatty Acids, Nonesterified ; Humans ; Hydrocortisone ; Hypoglycemia* ; Maintenance Chemotherapy ; Male ; Methotrexate ; Precursor Cell Lymphoblastic Leukemia-Lymphoma*

OBJECTIVE: To investigate the effects of sera from rats fed with tablets (HGT) on endoplasmic reticulum (ER) stress in a steatotic hepatocyte model of free fatty acids (FFAs)-induced nonalcoholic fatty liver disease (NAFLD) and explore the possible mechanism. METHODS: FFAs prepared by mixing oleic acid and palmitic acid at the ratio of 2:1. HepG2 cells were treated with the sera from rats fed with low-, moderate-or high-dose HGT (HGT sera) or sera of rats fed with fenofibrate (fenofibrate sera), followed by treatment with 1 mmol/L FFAs for 24 h to induce hepatic steatosis. Oil red O staining was used to observe the distribution of lipid droplets in the cells. The biochemical parameters including triglyceride (TG), lactated hydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured using a commercial kit. The morphological changes of the ER in the cells were observed using transmission electron microscopy. The protein/mRNA expressions of ER stress-related signal molecules including GRP78, PERK, p-PERK, ATF6, ATF4, CASPASE-12, CHOP, XBP-1, PKC, and p-PKC-δ were detected using Western blotting and/or quantitative real-time PCR (qRT-PCR). The changes in the protein expressions of GRP78, p-PERK, CASPASE-12 and CHOP were also detected in cells with transient transfection of PKC-δ siRNA for PKC-δ knockdown. RESULTS: Compared with the control cells, the cells treated with FFAs showed significantly increased levels of TG, AST, and ALT ( < 0.05). Compared with FFAs-treated cells, the cells pretreated with HGT sera or fenofibrate sera all showed significantly decreased TG, AST and ALT levels ( < 0.05), reduced accumulation of the lipid droplets ( < 0.05), and lowered protein or mRNA expression levels of GRP78, p-PERK, ATF6, ATF4, CHOP, CASPASE-12, XBP-1 and p-PKC-δ ( < 0.05). PKC-δ knockdown caused significantly reduced protein expressions of GRP78, p-PERK, CASPASE-12 and CHOP in the cells with FFA-induced hepatic steatosis ( < 0.001); treatment with high-dose HGT serum more significantly reduced the expressions of GRP78 ( < 0.001) and P-PERK ( < 0.01) in FFAs-induced cells with PKC-δ knockdown. CONCLUSIONS HGT serum can effectively prevent FFAs-induced steatosis in HepG2 cells by alleviating ER stress, in which PKC-δ may act as an important target.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Endoplasmic Reticulum ; ultrastructure ; Endoplasmic Reticulum Stress ; drug effects ; Fatty Acids, Nonesterified ; Fenofibrate ; administration & dosage ; Hep G2 Cells ; Humans ; Hypolipidemic Agents ; administration & dosage ; Microscopy, Electron, Transmission ; Non-alcoholic Fatty Liver Disease ; blood ; etiology ; prevention & control ; RNA, Messenger ; blood ; Rats ; Serum ; Tablets ; Triglycerides ; blood

Animals ; Body Weight ; physiology ; Computational Biology ; methods ; Disease Models, Animal ; Doxorubicin ; toxicity ; Fatty Acids, Monounsaturated ; blood ; metabolism ; Glomerulosclerosis, Focal Segmental ; blood ; chemically induced ; metabolism ; Male ; Methoxyhydroxyphenylglycol ; analogs & derivatives ; blood ; metabolism ; Mice ; Mice, Inbred BALB C ; Pyridoxine ; blood ; metabolism ; Valine ; analogs & derivatives ; blood ; metabolism ; Vanillic Acid ; blood ; metabolism

Medium-chain fatty acids (MCFAs) are mostly generated from dietary triglycerides and can penetrate the blood-brain barrier. Astrocytes in the brain use MCFAs as an alternative energy source. In addition, MCFAs have various regulatory and signaling functions in astrocytes. However, it is unclear how astrocytes sense and take up MCFAs. This study demonstrates that decanoic acid (DA; C10), a saturated MCFA and a ligand of G(αs) protein-coupled receptors (G(αs)-GPCRs), is a signaling molecule in energy metabolism in primary astrocytes. cAMP synthesis and lactate release were increased via a putative G(αs)-GPCR and transmembrane adenylyl cyclase upon short-term treatment with DA. By contrast, monoamine oxidase B-dependent gamma-aminobutyric acid (GABA) synthesis was increased in primary cortical and hypothalamic astrocytes upon long-term treatment with DA. Thus, astrocytes respond to DA by synthesizing cAMP and releasing lactate upon short-term treatment, and by synthesizing and releasing GABA upon long-term treatment, similar to reactive astrocytes. Our data suggest that astrocytes in the brain play crucial roles in lipid-sensing via GPCRs and modulate neuronal metabolism or activity by releasing lactate via astrocyte-neuron lactate shuttle or GABA to influence neighboring neurons.
Adenylyl Cyclases ; Animals ; Astrocytes* ; Blood-Brain Barrier ; Brain ; Energy Metabolism ; Fatty Acids ; gamma-Aminobutyric Acid* ; Lactic Acid* ; Metabolism ; Mice* ; Monoamine Oxidase ; Neurons ; Triglycerides

BACKGROUND: The levels of erythrocyte polyunsaturated fatty acids (FAs) may be associated with obesity, metabolic syndrome, and cancer. Thus, we investigated the association between erythrocyte n−3 and n−6 FA composition, body mass index (BMI), and biochemical profiles. METHODS: The body composition, dietary intake, and blood parameters, including serum lipid, glucose, insulin, adipokines, oxidative stress, and erythrocyte FA, were assessed in 66 overweight and obese women (average age, 43.4 years). We also classified the participants into the overweight, obese, and morbidly obese (MO) groups based on the BMI values of 23, 25, and 30 kg/m₂, respectively. Erythrocyte FA was measured via gas chromatography. RESULTS: The serum glucose, triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels of the participants in the overweight, obese, and MO groups were not significantly different. However, the serum insulin, high-density lipoprotein, cholesterol and leptin levels were significantly different. The erythrocyte n−6/n−3 ratios of the overweight, obese, and MO groups were 2.4, 2.5, and 2.8, respectively. These data were consistent with the dietary n−6/n−3 ratio findings. Moreover, the erythrocyte n−6/n−3 ratio was correlated with serum insulin levels. CONCLUSIONS: As the severity of obesity increased, the levels of insulin and leptin and the ratio of dietary n−6/n−3 increased, which was consistent with erythrocyte FA. These results indicate that erythrocyte FA may be a predictive biomarker for the increased prevalence of obesity, insulin resistance, leptin resistance, and risk of developing metabolic disorders.
Adipokines ; Blood Glucose ; Body Composition ; Cholesterol ; Chromatography, Gas ; Erythrocyte Membrane* ; Erythrocytes* ; Fatty Acids ; Fatty Acids, Unsaturated* ; Female ; Glucose ; Humans ; Insulin ; Insulin Resistance ; Leptin ; Lipoproteins ; Obesity ; Overweight* ; Oxidative Stress ; Prevalence ; Triglycerides