Increased Serum Triglyceride Research Articles

The Physiological Effects of Visfatin on Immune Response and Inflammatory Impacts on Nephropathy.

Obesity triggers the development of adipokines such as leptin, resistin, and visfatin, which have been associated with the development of diabetic nephropathy and other vascular disorders. The main purpose of the current investigation was to identify the physiological impact of visfatin on immunological response and its inflammatory effects on nephropathy. Fifty Iraqi patients with chronic kidney disease (CKD) at various stages, as described by the National Kidney Foundation (NKF) and ranging in age from 48.367.56 to 53.68 8.46 years on average were considered. Prior to the start of the investigation, informed consent was obtained from all participants, and the ethics committee approved the study. Patients were classified into two groups: Group (A) comprised patients with a GFR higher than 60 mL/minute, and Group (B) comprised patients with a GFR of less than 60 mL/min. There was no considerable variance between the groups as regards visfatin, but a highly significant correlation between serum visfatin and CRP was observed. The results of the current investigation indicated that serum visfatin levels are significantly correlated with CRP in CKD patients; it is also correlated with deterioration of kidney function. Moreover, higher visfatin levels were accompanied by increased serum triglyceride and cholesterol levels. These findings would suggest that visfatin may perform an essential function in uremia-related inflammation and may serve as a potential target for treatment and prevention of renal associated complications. Future studies may delineate whether visfatin is a marker of disease activity and severity as well as a predictor of outcome in CKD.

Effects of Bacillus subtilis on growth performance, serum parameters, digestive enzyme, intestinal morphology, and colonic microbiota in piglets

The present study was conducted to investigate effects of Bacillus subtilis on growth performance, serum parameters, digestive enzymes, intestinal morphology, and colonic microbiota in piglets. A total of 72 piglets were weighed and randomly allotted into three treatments (four replication pens per treatment with six piglets/pen) for a 28-day experiment. The dietary treatments were as follows: basal diet (control group, CTR), basal diet supplementation with antibiotic (antibiotic group, ABT), and basal diet supplementation with 0.1% Bacillus subtilis (probiotic group, PBT). The average daily gain of body weight increased in both the ABT and PBT groups, and dietary antibiotics decreased the feed:gain ratio (F:G), as compared to the CTR group (P < 0.05). Both ABT and PBT piglets had increased serum triglycerides and lipase, amylase, maltase activities and villus height:crypt depth ratio (V/C) in ileum (P < 0.05). The PBT group also showed an increase in serum glucose and villus height in the ileum (P < 0.05). Dietary antibiotics increased Lactobacillus johnsonii, as compared to the CTR group, but decreased bacterial diversity and increased Escherichia coli, as compared to the PBT group (P < 0.05). Piglets dietary with B. subtilis modulated the microbiota by increasing the abundance of Firmicutes (L. johnsonii, L. reuteri) and decreasing the abundance of E. coli, as compared to the control group (P < 0.05). These results indicate that dietary of B. subtilis improves growth performance and intestinal health and can be a promising alternative to antibiotics in piglets diet.

Valine Supplementation Does Not Reduce Lipid Accumulation and Improve Insulin Sensitivity in Mice Fed High-Fat Diet.

Branched-chain amino acids (BCAAs), particularly leucine, were reported to decrease obesity and relevant metabolic syndrome. However, whether valine has a similar effect has rarely been investigated. In the present study, mice were assigned into four treatments (n = 10): chow diet supplemented with water (CW) or valine (CV) and high-fat diet supplemented with water (HW) or valine (HV). Valine (3%, w/v) was supplied in the drinking water. The results showed that valine treatment markedly increased serum triglyceride and insulin levels of chow diet-fed mice. The body weight, serum triglyceride level, white adipose tissue weight, and glucose and insulin intolerance were significantly elevated by valine supplementation in high-fat diet-fed mice. Metabolomics and transcriptomics showed that several genes related to fat oxidation were downregulated, and arachidonic acid and linoleic acid metabolism were altered in the HV group compared to the HW group. In conclusion, valine supplementation did not suppress lipid deposition and metabolic disorders in mice, which provides a new understanding for BCAAs in the modulation of lipid metabolism.

Inflammatory cytokines and lipid profile in children and adolescents with nephrotic syndrome receiving L. Plantarum: a randomized, controlled feasibility trial.

This study aimed to evaluate the efficacy of the action of the Lactobacillus Plantarum probiotic as a immunomodulatory and hypolipidemic agent in dyslipidemic nephrotic children and adolescents. This is a randomized, double-blind, placebo-controlled clinical trial in pediatric, compensated or partially compensated nephrotic syndrome and dyslipidemic subjects undergoing regular outpatient follow-up. Serum lipid and TNF-α (proinflammatory) and IL-10 (anti-inflammatory) cytokine variations were evaluated. Cytokines were analyzed by enzyme-linked immunosorbent assay (ELISA). In the probiotic group there was a tendency to reduce TNF-α levels and increase IL-10 levels when compared to controls. Regarding the lipid profile, there was a decrease in serum triglyceride (6.0 mg / dL) and total cholesterol (41.5 mg / dL) levels in the probiotic group when compared to baseline levels, while in the control group there was an increase in serum triglyceride (49.5 mg / dL) and total cholesterol (8.0 mg / dL) levels, respectively. Preliminary results suggest that L. Plantarum showed an immunomodulatory and hypolipidemic effect in nephrotic and dyslipidemic pediatric subjects.

Cryptotanshinone alleviates chemotherapy-induced colitis in mice with colon cancer via regulating fecal-bacteria-related lipid metabolism

Patients with colorectal cancer treated with 5-fluorouracil (5-FU) and irinotecan (CPT-11) exhibit a risk for chemotherapy-induced colitis (CIC) that may lead to fatal consequences. Cryptotanshinone (CTS) is a natural compound extracted from the root of Salvia miltiorrhiza Bunge that shows potent antitumor activities. We previously reported CTS relieved 5-FU/ CPT-11 induced colitis in tumor-free mice. In this study, we studied the effect of CTS on 5-FU/ CPT-11 induced colitis in mice with colitis associated colon cancer (CAC). The effects of CTS on CIC were evaluated by disease activity index (DAI) and histological assessment via hematoxylin-and-eosin staining. Serum lipids and lipid-metabolic enzymes were detected by commercial kits. Fecal microbial diversity was detected by 16S ribosomal RNA gene sequencing. To find the role of fecal bacteria in CAC mice with 5-FU/ CPT-11 induced colitis, pseudo-germ-free mice were established by intragastric administration of mixed antibiotics. Except for decreasing tumor number (3 ± 1 vs 6 ± 1, p < 0.05), CTS significantly alleviated DAI (1.9 ± 0.6 vs 2.6 ± 0.5, p < 0.05) and regulated serum lipids in CAC mice with 5-FU/ CPT-11induced colitis. Compared with model group, CTS significantly increased serum triglycerides (TG) (1.13 ± 0.26 mM vs 0.79 ± 0.03 mM, p < 0.05), high density lipoprotein (HDL) (3.88 ± 0.1 mM vs 3.28 ± 0.05 mM, p < 0.001) and oxidized low-density lipoprotein (oxLDL) (288.12 ± 65.92 ng/mL vs 150.72 ± 42.13 ng/mL, p < 0.05) level but decreased serum adiponectin level (1177.47 ± 179.2 pg/mL vs 1523.43 ± 91.8 pg/mL, p < 0.05). Among fecal bacteria significantly correlated with lipid metabolism, CTS significantly decreased the abundance of g__norank_f__Muribaculaceae (21.15 % ± 5.7 % vs 41.84 ± 12.0 %, p < 0.01) but increased that of g_Lactobacillus (11.13 % ± 6.6 % vs 5.7 % ± 4.6 %, p < 0.05), g__Alistipes (3.66 % ± 0.7 % vs 1.47 % ± 1,0%, p < 0.01) and g__Odoribacter (1.31 % ± 0.7 % vs 0.30 % ± 0.2 %, p < 0.01). In addition, the development of CIC and abnormal lipid metabolism were significantly prevented in pseudo-germ-free mice. Therefore, we concluded CTS alleviated 5FU/CPT-11 induced colitis in CAC mice via regulating fecal flora associated lipid metabolism.

Risk factors for subclinical renal damage and its progression: Hanzhong Adolescent Hypertension Study.

Chronic kidney disease (CKD) is a global public health problem, including in China. The aim of this study was to identify the risk factors for the development and progression of subclinical renal disease (SRD) in a Chinese population. We also examined whether the impact of the risk factors on SRD changed over time. To identify the predictors of SRD, we performed a cross-sectional study of the 2432 subjects in our Hanzhong Adolescent Hypertension Cohort. A subgroup of 202 subjects was further analyzed over a 12-year period from 2005 to 2017 to determine the risk factors for the development and progression of SRD. In cross-sectional analysis, elevated blood pressure, male gender, diabetes, body mass index, and triglyceride were independently associated with a higher risk of SRD. In longitudinal analysis, an increase in total cholesterol over a 4-year period and an increase in serum triglyceride over a 12-year period were independently associated with progression of albuminuria. Finally, increases in both total cholesterol and serum uric acid over a 4-year follow-up showed an independent association with a modest reduction in estimated glomerular filtration rate (eGFR). In this study of a Chinese cohort, we show several metabolic abnormalities as independent risk factors for subclinical renal disease in a Chinese cohort. In addition, we demonstrate that the effects of total cholesterol, triglycerides and uric acid on the development and progression of albuminuria or the decline in eGFR vary at different points of follow-up. These findings highlight the importance of early detection of metabolic abnormalities to prevent SRD.

Tobacco Smoking and Association between Betel Nut Chewing and Metabolic Abnormalities Among Military Males: The CHIEF Study.

To investigate the effect of smoking and alcohol intake on the association between betel nut chewing and each metabolic abnormality. Betel nut chewing has been associated with metabolic syndrome. Whether the association is affected by tobacco or alcohol use is not clarified so far. The authors conducted a cross-sectional study using 6,657 military males, aged 18-50 years in eastern Taiwan in 2013-2014. Metabolic syndrome was defined according to the International Diabetes Federation's ethnic criteria for Asians. The population was classified as non-betel nut chewers (N =5,749), current chewers with both tobacco and alcohol use (N =615), and current chewers without tobacco and/or alcohol use (N =293). Multiple logistic regression analyses were stepwise adjusted for the confounders including alcohol and tobacco use to determine the association of betel chewing with the metabolic abnormalities. As compared to the non-current chewers, the current chewers with both tobacco/alcohol use and those without had a higher risk of metabolic syndrome (odds ratios (OR) and 95% confidence intervals: 2.46 (2.00-3.02), and 2.04 (1.53-2.73), respectively) after controlling for age, service specialty, total cholesterol levels ≥200 mg/dL and exercise frequency (model 1). The association did not change much in the two chewing groups after additionally adjusting for alcohol consumption (model 2) (OR: 2.49 (1.99-3.12), and 2.04 (1.52-2.73), respectively), whereas the relationship reduced significantly in the chewers with both tobacco/alcohol use rather than those without after further adjusting for smoking (model 3) (OR: 2.18 (1.71-2.78) and 2.02 (1.51-2.71), respectively). This was in parallel with the pattern for the association of betel nut chewing with serum triglycerides >150 mg/dL in the chewers with both tobacco/alcohol use and those without in model 1 (OR: 2.90 (2.40-3.51) and 1.90 (1.45-2.49), respectively, p =0.011), in model 2 (OR: 2.82 (2.30-3.46) and 1.89 (1.44-2.49), respectively, p =0.040), and in model 3 (2.26 (1.81-2.81) and 1.87 (1.42-2.45), respectively, p =0.76). Our findings suggest that tobacco smoking but not alcohol intake could increase the relationship of betel nut chewing with metabolic syndrome, which is likely mediated by a synergic effect on increasing serum triglycerides levels.

Abstract 394: LXR agonist N,N-dimethyl-3-β-hydroxy-cholenamide, DMHCA, reduces ErbB2-dependent tumorigenesis and immune tolerance in a conditional model of mammary fibrosis

Abstract Background: One of the central challenges for cancer therapy is the identification of factors in the tumor microenvironment that increase tumor progression and prevent the immune system from eradicating the tumor. One such factor associated with breast cancer is stromal fibrosis, a histopathologic criterion for invasive cancer and poor survival. Fibrosis is caused by inflammatory factors and remodeling of the extracellular matrix, which results in excessive collagen deposition and an immune tolerant environment. Experimental Procedures: We developed a novel transgenic model representative of HER2/ErbB2+ breast cancer, termed NeuT/ATTAC, in which partial ablation of mammary fat resulted in its replacement with fibrotic tissue. NeuT/ATTAC mice were administered a diet supplemented with 0.04% DMHCA, a desmosterol-like pan agonist of the liver X receptor (LXR). Collagen deposition resulting from fibrosis was assessed by second harmonic generation (SHG) fluorescence microscopy and histological staining, immune cell subsets were analyzed by fluorescence-activated cell sorting and biomarkers of fibrosis, proliferation and immune tolerance were determined by IHC. Findings: Administration of DMHCA to NeuT/ATTAC mice beginning at two months of age reduced tumorigenesis, tumor multiplicity and suppressed fibrosis as shown by loss of collagen, fibroblast activation protein (FAP) and α-smooth muscle actin (SMA). These changes were accompanied by a marked reduction in the percentage of MDSC, and an increase in CD8+ effector T cells and PD1+/Foxp3+ CD4 T cells. Conclusion: Reduction of fibrosis, tumorigenesis and immune tolerance by DMHCA suggests that this LXR agonist may be useful for reducing tumor-associated fibrosis and in combination with immune checkpoint inhibitors that target PD1+ Treg cells for moderating immune tolerance. Unlike non-steroidal LXR agonists, DMHCA does not increase serum triglycerides or produce hepatic steatosis, and may therefore be a good candidate for clinical studies. Supported by a Sher Award, 1P30CA051008 from the NCI, NIH, to the Lombardi Comprehensive Cancer Center, and R01 HL133545 and R01 DK116567 from the NIH to M.L. Citation Format: Robert I. Glazer, Gao Sheng, Hongyan Yuan, Suman Ranjit, Jin Lu, Xun Lu, Moshe Levi. LXR agonist N,N-dimethyl-3-β-hydroxy-cholenamide, DMHCA, reduces ErbB2-dependent tumorigenesis and immune tolerance in a conditional model of mammary fibrosis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 394.

Evaluating acute inflammation's effects on hepatic triglyceride content in experimentally induced hyperlipidemic dairy cows in late lactation

Inflammation appears to be a predisposing factor and key component of hepatic steatosis in a variety of species. Objectives were to evaluate effects of inflammation [induced via intravenous lipopolysaccharide (LPS) infusion] on metabolism and liver lipid content in experimentally induced hyperlipidemic lactating cows. Cows (765 ± 32 kg of body weight; 273 ± 35 d in milk) were enrolled in 2 experimental periods (P); during P1 (5 d), baseline data were obtained. At the start of P2 (2 d), cows were assigned to 1 of 2 treatments: (1) intralipid plus control (IL-CON; 3 mL of saline; n = 5) or (2) intralipid plus LPS (IL-LPS; 0.375 μg of LPS/kg of body weight; n = 5). Directly following intravenous bolus (saline or LPS) administration, intralipid (20% fat emulsion) was intravenously infused continuously (200 mL/h) for 16 h to induce hyperlipidemia during which feed was removed. Blood samples were collected at -0.5, 0, 4, 8, 12, 16, 24, and 48 h relative to bolus administration, and liver biopsies were obtained on d 1 of P1 and at 16 and 48 h after the bolus. By experimental design (feed was removed during the first 16 h of d 1), dry matter intake decreased in both treatments on d 1 of P2, but the magnitude of reduction was greater in LPS cows. Dry matter intake of IL-LPS remained decreased on d 2 of P2, whereas IL-CON cows returned to baseline. Milk yield decreased in both treatments during P2, but the extent and duration was longer in LPS-infused cows. Administering LPS increased circulating LPS-binding protein (2-fold) at 8 h after bolus, after which it markedly decreased (84%) below baseline for the remainder of P2. Serum amyloid A concentrations progressively increased throughout P2 in IL-LPS cows (3-fold, relative to controls). Lipid infusion gradually increased nonesterified fatty acids and triglycerides in both treatments relative to baseline (3- and 2.5-fold, respectively). Interestingly, LPS infusion blunted the peak in nonesterified fatty acids, such that concentrations peaked (43%) higher in IL-CON compared with IL-LPS cows and heightened the increase in serum triglycerides (1.5-fold greater relative to controls). Liver fat content remained similar in IL-LPS relative to P1 at 16 h; however, hyperlipidemia alone (IL-CON) increased liver fat (36% relative to P1). No treatment differences in liver fat were observed at 48 h. In IL-LPS cows, circulating insulin increased markedly at 4 h after bolus (2-fold relative to IL-CON), and then gradually decreased during the 16 h of lipid infusion. Inducing inflammation with simultaneous hyperlipidemia altered the characteristic patterns of insulin and LPS-binding protein but did not cause fatty liver.

Lack of collagen XVIII leads to lipodystrophy and perturbs hepatic glucose and lipid homeostasis.

Lack of collagen XVIII leads to lipodystrophy and perturbs hepatic glucose and lipid homeostasis.

Reliability And Validity Of A Mobile Setup For Metabolic Syndrome Diagnosis Using Point-of-care Analyzers

The metabolic syndrome (MetS) is a worldwide public health concern and is characterized by having three or more of these risk factors: high blood glucose (Glc), increased waist circumference (WC), high blood pressure (BP), reduced serum high-density lipoprotein (HDL) and increased serum triglycerides (TG). As certain rural regions lack the required infrastructure for optimal medical care, mobile diagnostics using point-of-care analyzers could help by identifying people at risk for MetS. PURPOSE: Test the reliability and validity of MetS risk factor analysis using point-of-care analyzers in a mobile examination unit. METHODS: Fifty participants (18 test-retest; 52±7 y; 170±10 cm; 80±19 kg) were enrolled in the study. Agreement of Glc, HDL and TG of three point-of-care analyzers (A, B, C) against a reference lab (REF) were analyzed by Bland-Altman (bias, Limits of Agreement (LoA)) and McNemar’s test (MN). Further, MetS diagnosis by the mobile setup was tested for inter-session reliability by Spearman’s rho and test-retest variability (TRV%). RESULTS: The range of systematic bias was for Glc -21 to -8 mg/dl, for TG -90 to 3 mg/dl and for HDL -8 to 9 mg/dl. Device C was excluded from further analyses due to missing values. Device A was chosen for additional analysis based on smallest bias and LoA (Glc: -8 [LoA -27 to 11] mg/dl; TG: 3 [LoA -40 to 46] mg/dl; HDL: -3 [LoA -16 to 11] mg/dl) and best agreement of MetS diagnosis with REF (MN: A vs. REF: p>.05; B vs. REF: p<.05). Test-retest analysis for risk factor classification and MetS diagnosis was performed in a mobile examination unit using device A. No inter-session differences for risk factor and MetS diagnosis were shown (MN day 1 vs. 2: p>.05). Spearman’s rho and TRV for risk factors were: TG: r =.734 (p<.05); 3.3%; HDL: r =.893 (p<.05); 6.8%; Glc, r =.076; 1.9%; systolic BP: r =.372; 1.7%; diastolic BP: r =.457; 3.3% and WC: r =.950 (p<.05); 1.1%. CONCLUSIONS: The mobile setup showed no inter-session difference in MetS diagnosis. TRV was low for all risk factors and test-retest reliability was acceptable for TG, good for HDL and excellent for WC. Inter-session variations in Glc and BP did not influence the overall risk factor classification and MetS diagnosis. A mobile setup using a point-of-care analyzer for blood analysis is a valid and reliable method for a near-to-home MetS screening.

Genome-wide Association Study of the Postprandial Triglyceride Response Yields Common Genetic Variation in Hepatic Lipase (LIPC)

The increase in serum triglyceride (TG) concentrations in response to a meal is considered a risk factor for cardiovascular disease. We aimed to elucidate the genetics of the postprandial TG response through genome-wide association studies (GWAS). Participants of the NEO (Netherlands Epidemiology of Obesity) study (n=5630) consumed a liquid mixed meal after an overnight fast. GWAS of fasting and postprandial serum TG at 150 minutes were performed. To identify genetic variation of postprandial TG independent of fasting TG, we calculated the TG response at 150 minutes by the residuals of a nonlinear regression that predicted TG at 150 minutes as a function of fasting TG. Association analyses were adjusted for age, sex, and principal components in a linear regression model. Next, using the identified variants as determinants, we performed linear regression analyses on the residuals of the postprandial response of 149 nuclear magnetic resonance-based metabolite measures. GWAS of fasting TG and postprandial serum TG at 150 minutes resulted in completely overlapping loci, replicating previous GWAS. From GWAS of the TG response, we identified rs7350789-A (allele frequency=0.36), mapping to hepatic lipase (LIPC), to be associated with a smaller increase in TG concentrations at 150 minutes (β=-0.11; P-value=5.1×10-8). Rs7350789-A was associated with responses of 33 metabolite measures (P-value <1.34×10-3), mainly smaller increases of the TG-component in almost all HDL (high-density lipoprotein) subparticles (HDL-TG), a smaller decrease of HDL diameter and smaller increases of most components of VLDL (very low density lipoprotein) subparticles. GWAS of the TG response identified a variant near LIPC as a main contributor to postprandial TG metabolism independent of fasting TG concentrations, resulting in smaller increases of HDL-TG and VLDL subparticles.

Cottonseed Meal Bioactive Peptides as an Alternative to Antibiotic Growth Promoters in Broiler Chicks

The aim of this experiment was to evaluate the effects of bioactive peptides derived from enzymatic hydrolysis of cottonseed meal (CSBP) compared with zinc bacitracin, as an antibiotic growth promoter (AGP), on productive traits, serum lipid profile, and ileal microbial population in broiler chickens. A total number of 240-day-old broiler chicks (Ross 308) were allocated into 4 treatments, replicated 5 times based on a completely randomized design. The dietary treatments included a basal diet serving as control group, basal diet + 40 mg/kg zinc bacitracin as AGP group, and the basal diet supplemented with 15 or 20 g/kg CSBP substituting equal quantity of maize and soybean meal. Performance traits, including daily weight gain, feed intake, feed conversion ratio (FCR), and livability were recorded. At the end of the study, serum lipid parameters, ileal microbial population, and economical indices were determined. The results indicated that feed intake and FCR increased (P < 0.05) in birds receiving 20 g/kg CSBP over the entire period (1–35 days), but there was no significant effect of CSBP on body weight, although numerically higher than the control group. However, the antibiotic group showed a significant increase (P < 0.05) in body weight and feed intake. Livability, European Production Efficiency Factor (EPEF), and European Broiler Index (EBI) significantly improved in broiler chickens fed antibiotic and 15 g/kg CSBP supplement (P < 0.05). Adding 20 g/kg of CSBP to the diet significantly increased serum triglycerides and decreased low-density lipoproteins (LDL) compared to the control and antibiotic groups on day 35. The relative weight of abdominal fat and LDL to HDL ratio were significantly lower for CSBP and antibiotic treatments than the control group (P < 0.05). Supplementation of antibiotic and both graded levels of CSBP decreased the ileum population of Escherichia coli (P < 0.05). The current findings suggest that including CSBP in broiler diets may benefit production through improving growth rate of broilers and balancing gut microbiota population. In addition, CSBP could be considered as a potential alternative to antibiotics in an AGP free production system.

Lipid profile of regular kratom (Mitragyna speciosa Korth.) users in the community setting.

Background and aimKratom, or Mitragyna speciosa Korth., is a tropical plant that has been reported to exhibit opioid-like effects. Although opioids have been demonstrated to alter the lipid profile of regular users, data on the lipid-altering effects of kratom are scarce. This study aimed to compare the fasting lipid profile of regular kratom users to that of healthy subjects who do not use kratom. It also determined the association between various characteristics of kratom users and the serum triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels of regular kratom users.MethodsA total of 200 participants (n = 100 kratom users and n = 100 healthy subjects who do not use kratom) were recruited for this analytical cross-sectional study. Data on sociodemographic status, kratom use characteristics, cigarette smoking, physical activity, body mass index (BMI), fasting serum lipid profile, and liver function were collected from all participants.ResultsThe liver parameters of the study participants were within normal range. The serum total cholesterol and LDL of kratom users were significantly lower than those of healthy subjects who do not use kratom. There were no significant differences in the serum triglyceride and HDL levels. However, higher average daily frequency of kratom use and increasing age were associated with increased serum total cholesterol among kratom users. Other kratom use characteristics such as age of first kratom intake, duration of kratom use, and quantity of daily kratom intake were not associated with increased serum triglyceride, total cholesterol, LDL, and HDL levels.ConclusionsOur findings suggest regular kratom consumption was not linked to elevated serum lipids, except when there is a higher frequency of daily kratom intake. However, the study was limited by the small sample size, and hence a more comprehensive study with larger sample size is warranted to confirm the findings.

582-P: Triglycerides, Uric Acid, and Incidence of Type 2 Diabetes Mellitus in Northwest China: The Jinchang Cohort Study

Objective: To study the association of triglycerides(TG), uric acid and incidence of type 2 diabetes mellitus(T2DM), evaluate whether there would be an additive interaction between two factors. Methods: Based on the follow-up population of Jinchang cohort, an ongoing occupational-based prospective cohort study of 48,001 participants at baseline, the nested-case control study was used to explore the relationship of TG, uric acid and incidence of T2DM, and calculate the odds ratio(OR) and 95% confidence intervals(CI). The interaction additive model was used to evaluate whether there would be an additive interaction between two factors. Results: Among 18,195 participants with normal fasting plasma glucose(FPG) at baseline, there were 267 incident diabetes cases during a median of 2.2 years of follow-up. With the increase of serum TG and uric acid, the cumulative incidences of diabetes in people with normal FPG at baseline were all rising (P for trend&amp;lt;0.05). After multivariable adjustments, the risk factors of diabetes were overweight/obesity(OR=2.30, 95%CI:1.72-3.08), hypertension(OR=2.42, 95%CI:1.78-3.29),hypertriglyceridemia(OR=1.49,95%CI:1.11-2.00), hyperuricemia(OR=2.32,95%CI:1.62-3.30), hypo high density lipoprotein cholesterolemia(OR=2.35, 95%CI:1.60-3.46). There was a positive additive interaction between hypertriglyceridemia and hyperuricemia on the development of diabetes from normal FPG. When they were co-existing, the risk of diabetes(OR, 95%CI) in the total, male and female population were 7.13 (4.70-10.83), 8.42 (5.13-13.83) and 7.09 (2.94-17.14),respectively. Conclusion: Increased triglycerides and uric acid were strong risk factors of diabetes. Furthermore, there was a positive additive interaction between hypertriglyceridemia and hyperuricemia on the development of diabetes from normal fasting plasma glucose. Disclosure W. Huang: None. J. Yang: None. N. Liu: None. P. Huang: None. R. Zhang: None. R. Wang: None. Z. Bai: None. N. Cheng: None. M. Wang: None. S. Zheng: None. Y. Bai: None. Funding National Institutes of Health (1R01ES02908201A1); Lanzhou University (2018LDBRZD008)

Window of Opportunity: Targeting ANGPTL4 Improves Triglyceride Levels in Maternal Obesity During Pregnancy.

During pregnancy, maternal dyslipidemia is a physiological response that provides fuel and nutrients for both the placenta and the developing fetus (1). Although less appreciated than glucose and amino acids, maternal lipids promote fetal growth and are essential for normal development (2). During the first and second trimester of pregnancy, fat accumulates in maternal tissues, and by the third trimester of pregnancy, maternal hyperlipidemia, defined here as increased serum triglycerides (TG) and total cholesterol (TC), is significantly elevated due to moderately increased maternal insulin resistance and lipolysis of lipids in adipose tissues as well as attenuated lipid uptake by peripheral tissues (Fig. 1 A ). Both TG and TC are taken up by the placenta, and placental lipases can hydrolyze TG to free fatty acids for fetal-placental availability (3). It is important to note that while both TG and TC levels rise throughout pregnancy, the TG increase is disproportionately higher in comparison with other lipid fractions and subsequently falls precipitously to prepregnancy levels following delivery (4). Figure 1 Physiological elevation in maternal blood TG in pregnancy is regulated by increased ANGPTL4 expression in mice. A : During normal pregnancy, maternal blood TG concentrations are increased in part by insulin resistance in peripheral tissues to ensure TG supply for the placenta and fetus. These alterations result in increased adipose tissue lipolysis, increasing the release of free fatty acids (FAs) and glycerol from adipose tissue and their transfer to the liver and the placenta. During pregnancy, increased expression of ANGPTL4 inhibits LPL, regulating TG clearance from the blood serum. ANGPTL4 expression is increased during pregnancy in inguinal …

MON-642 Genetic Knockout of Intestinal Hexokinase Domain-Containing Protein 1 Affects Whole-Body Glycemic Control and Triglyceride Metabolism

Hexokinase domain-containing protein 1 (HKDC1) is a recently discovered putative fifth hexokinase that is widely expressed in a variety of human and mouse tissues. Previous work indicate that HKDC1 is important for whole-body glucose homeostasis and utilization in pregnancy and aging, and suggest roles for HKDC1 in nonalcoholic fatty liver disease development and progression of hepatocellular carcinoma. Prior work in the lab further showed that global heterozygous-deleted HKDC1 mice exhibit blunted uptake of triglycerides following an olive oil bolus compared to wild-type mice, suggesting a role for intestinal HKDC1 expression in intestinal lipid metabolism (unpublished results). To specifically study the significance of intestinal HKDC1 on whole-body glucose and lipid homeostasis, we utilized Cre-mediated recombination of HKDC1 in which Cre was expressed under the control of the villin gene promoter, creating a mouse model in which HKDC1 expression is specifically deleted in the intestinal epithelium. Quantitative RT-PCR data confirmed the knockout of HKDC1 within the mouse intestine in young and aged mice, while HKDC1 expression in other tissues was comparable to wild-type mice. Next, intestinal HKDC1 knockout mice and their wild-type littermate controls were either maintained on a normal diet or were switched to a high fat diet at 6 weeks of age to simulate the state of impaired glucose tolerance, and the effects of intestinal HKDC1 on glucose and lipid homeostasis were analyzed between 28-34 weeks of age. Mice fed a normal diet did not exhibit any differences in serum glucose or triglyceride during oral/intraperitoneal glucose tolerance tests or oral olive oil bolus, respectively, regardless of intestinal HKDC1 status. Interestingly, mice lacking intestinal HKDC1 that were on a high fat diet demonstrated improved overall glycemic control compared to wild-type mice after the administration of an oral glucose load, all while there were no changes in insulin levels, gluconeogenesis or insulin tolerance related to HKDC1 status. Additionally, introduction of an intraperitoneal glucose load to mice fed a high fat diet did not alter glucose control in the presence or absence of intestinal HKDC1. However, high fat diet-fed mice lacking intestinal HKDC1 did not have a significant increase in serum triglyceride following an oral olive oil bolus, while their stool fat and triglyceride content were comparable to wild-type. Collectively, these data indicate that intestinal HKDC1 has important roles in glucose and triglyceride metabolism within the intestinal epithelium, and further suggest a role in whole-body glucose homeostasis and in the development of insulin resistance and diabetes.

SUN-582 Effect of the Combination of Conjugated Estrogens and Bazedoxifene on Muscle and Serum Lipidome in Obese Postmenopausal Women: A Placebo-Controlled Randomized Pilot Trial

Background and Objectives: Menopause is characterized by estrogen deficiency and predisposes women to weight gain and metabolic disturbances including lipid abnormalities. Orally-administered estrogens increase high-density lipoprotein (HDL) and triglycerides (TG) cholesterol and decreases low-density lipoprotein (LDL) cholesterol levels. The increase in serum TGs is not well understood. The objective of this study was to assess the effect of CE/BZA on serum and skeletal muscle lipid species in obese postmenopausal women. Methods: Randomized double-blind crossover pilot trial in 8 obese postmenopausal women (53± 3 years, BMI 35.7±3.2 kg/m2) assigned to 8 weeks of CE/BZA or placebo with 8 weeks washout in between. At the end of each 8-week treatment period, intrahepatic and skeletal muscle lipids were measured by proton magnetic resonance spectroscopy (1H-MRS) while serum and skeletal muscle lipidomics were assayed by ultrahigh performance liquid chromatography/mass spectrometry (UHPLC/MS). Results: No treatment differences were observed in intrahepatic lipid, soleus intramyocellular lipid (IMCL) or extramyocellular lipid (EMCL) as well as tibialis anterior IMCL or EMCL.The serum metabolome and lipidome comprised a total of 2002 biochemicals. Treatment with CE/BZA was associated with higher levels of diacylglycerols (DAGs) and triacylglycerols (TAGs) composed of long-chain saturated fatty acids (SFA, palmitic C16:0 and arachidic C20:0), monounsaturated FAs (MUFA, palmitoleic C16:1, oleic C18:1 and ecosenoic C20:1), and polyunsaturated FAs (PUFA, linoleic C18:2, arachidonic C20:4, eicosapentaenoic C20:5, and docosahexaenoic C22:6) compared to placebo (all p<0.05). Treatment with CE/BZA was also associated with lower levels of several acylcarnitine species, which are markers of FA oxidation, including long-chain SFA (C14, C16 and C18), MUFA (C18:1 and C24:1) and PUFA (C18:2, C20:2 and C20:4). In addition, treatment with CE/BZA was associated with higher levels of phosphatidylcholines (PCs), phosphatidylinositols (PIs), phosphatidylethanolamines (PEs), sphingomyelins (SMs), and ceramides (CER), as well as lower levels of lysophophatidylcholines (LPCs). There were no treatment differences in carnitine or ketones levels. The skeletal muscle analysis comprised a total of 652 biochemicals, but unlike in serum, no significant treatment differences were observed in the skeletal muscle lipidome. Conclusions: Our lipidomic analysis supports a model in which CE/BZA (and likely all oral estrogens) increases hepatic de novo FA synthesis and esterification into TAGs for export into TAG-rich very low-density lipoproteins, as well as decreased FA oxidation, respectively. Although CE/BZA treatment inhibits FA oxidation, it is not associated with hepatic lipid accumulation as measured by MRS, or skeletal muscle lipid accumulation measured by MRS and lipidomics.

Health functionality of dietary oleogel in rats fed high-fat diet: A possibility for fat replacement in foods

This study was to determine the effect of oleogel on lipid metabolism in rats fed high-fat diet. Male SD rats (n = 32; 4-wk-old) and obese Zucker rats (n = 6) fed either beef tallow containing high fat diet (HFD) or beeswax oleogel containing canola oil (BOG) for 2 months. Substitution of 50% BT by BOG significantly reduced body weight. Increased serum triglyceride by HFD was reduced (P < 0.05) by BOG. Serum HDL cholesterol was increased (P < 0.05) by dietary BOG. HFD-induced increase in area of lipid and hepatic steatosis were decreased (P < 0.05) by BOG. Carnitine palmitoyltransferase-1 expression was upregulated in the visceral fat in BOG compare to HFD group. Angiogenesis genes, vascular endothelial growth factor and nitric oxide synthase, were also increased (P < 0.05) by BOG in Zucker rats. These results suggest that BOG effectively decreases adipogenesis and improves angiogenesis in obese rat model.

Inhibition of acetyl-CoA carboxylase by PP-7a exerts beneficial effects on metabolic dysregulation in a mouse model of diet-induced obesity.

Acetyl-coenzyme A carboxylase (ACC) is a critical regulator of fatty acid metabolism and represents a promising therapeutic target for metabolic diseases, including obesity, type 2 diabetes and non-alcoholic fatty liver disease. Recently, a novel ACC inhibitor, PP-7a, was developed by our group by utilizing a structure-based drug design. In the present study, the pharmacological effects of PP-7a on the metabolic dysregulation in mice with high-fat diet (HFD)-induced obesity and the underlying mechanisms were investigated. The inhibitory effect on ACC activities was confirmed by assessing the level of malonyl-CoA, a product synthesized by the catalyzation of ACC. Following 16 weeks of being fed an HFD, the mice were administered PP-7a (15, 45 or 75 mg/kg) for 4 weeks. The effects of PP-7a on weight gain, glucose intolerance, hepatic lipid accumulation and the increase of serum triglyceride (TG), total cholesterol (TC) and free fatty acids (FFA) in mice were assessed. CP-640186 was used as a positive control drug and administered in the same manner as PP-7a. Chronic administration of PP-7a lowered the malonyl-CoA levels in liver and heart tissues of mice in the HFD group. In addition, HFD-induced weight gain and glucose intolerance were improved by PP-7a treatment in the mice fed the HFD. Furthermore, PP-7a suppressed hepatic lipid accumulation and the increase in TG, TC and FFA levels. Taken together, these results suggest that ACC inhibition by PP-7a may have a beneficial effect on metabolic dysregulation in obese mice.