Weight Triglyceride Research Articles

Food security association with some risk factors of obesity-related diseases in Ardabil-Iran population

The aim of the study is the assessment of the food security status and its association with some risk factors of chronic obesity-related diseases in Ardabil-Iran population. METHODS: This cross-sectional study was done between 500 adults of Ardabil that were selected by random sampling from Persian cohort study participants, in January 2019. Food insecurity of study participants was measured using the United States Department of Agriculture 18-item questionnaire. Some risk factors of chronic diseases including fasting blood glucose, lipid profile, liver enzymes, and dietary information were measured on the day of the interview. To assess the association between variables the correlation and linear regression tests were used. RESULTS: Forty-eight and six percent of the study participants were food secure and 51.4% were in food insecurity status. There were a significant difference in weight, blood glucose, blood pressure, and serum triglyceride levels between the food security status groups (P < 0.05). The food insecurity score had significant association with participants, weight (p = 0.005,β= 1.66), serum triglycerides (p = 0.022,β= 0.027), body mass index (p = 0.003,β= 0.645) and fasting blood sugar (p = 0.0001,β= 0.664). CONCLUSION: About half of the participants were in food insecurity status. Food insecurity status can be associated with obesity and some risk factors of chronic obesity-related diseases. This problem requires main food policies to reduce food insecurity in the community.

Abstract 1463: Impaired reciprocal regulation between SIRT6 and TGF-β signaling as a potential mechanism for development and progression of fatty liver

Abstract Background: Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of fibrotic liver disease and hepatocellular carcinoma (HCC). Dysregulated TGF-β signaling and loss of SIRT6 activity are implicated in fatty liver disease. SIRT6 limits fibrosis by inhibiting SMAD3 activity and limits de novo lipogenesis by inhibiting SREBP1 and SREBP2 activity. We hypothesized that altered reciprocal regulation between TGF-β signaling and SIRT6 contributes to NAFLD and its progression. The goal of this study was to identify regulatory crosstalk between SIRT6 and SMAD3 and SPTBN1, a regulator of SMAD3 activity. Methods: We used bioinformatics and chromatin immunoprecipitation (ChIP) with HepG2 cells to examine the binding of SMAD3 or CTCF to the SIRT6 gene in the presence or absence of TGF-β. Using cultured cells, we examined the effect of altering SPTBN1 or SMAD3 on SIRT6 abundance, and of altering SIRT6 on SPTBN1 and SMAD3 abundance. We examined liver phenotypes of SPTBN1+/- mice fed either a normal chow diet or a high-fat diet (HFD) and monitored body weight and serum total cholesterol and triglyceride concentrations, as well as analyzed liver tissue for SIRT6 abundance. Results: We identified two consensus SMAD-binding elements and two consensus CTCF binding sites in the SIRT6 promoter and showed by ChIP that TGF-β stimulated SMAD3 and CTCF binding to the promoter region of SIRT6. We found that deficiency in SMAD3 or SPTBN1 reduced SIRT6 mRNA and protein abundance. Overexpression of SIRT6 reduced expression of selected TGF-β-induced genes. Knockdown of SIRT6 increased SPTBN1 but not SMAD3 abundance and overexpression of SIRT6 reduced only SPTBN1 abundance. We found that fatty liver and associated metabolic changes induced by HFD is worse in SPTBN1+/- mice than in control mice. Furthermore, this condition was associated with reduced SIRT6 protein abundance in the liver. Conclusions: We found a reciprocal regulatory mechanism involving SPTBN1 through which SIRT6 can influence TGF-β signaling and identified SIRT6 as a target of TGF-β-SMAD3 signaling. The development of liver steatosis with reduced SIRT6 in SPTBN1+/- mice suggested that impaired induction of SIRT6 contributes to the severe liver phenotype, which resembles nonalcoholic steatohepatitis (NASH). Future investigation may yield opportunities to intervene and prevent NAFLD from progressing to NASH and thus reduce the risk of HCC. Citation Format: Kazufumi Ohshiro, Xiyan Xiang, David Bernstein, James M. Crawford, Bibhuti Mishra, Patricia S. Latham, Nancy R. Gough, Shuyun Rao, Lopa Mishra. Impaired reciprocal regulation between SIRT6 and TGF-β signaling as a potential mechanism for development and progression of fatty liver [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1463.

Effects of ALT-801, a GLP-1 and glucagon receptor dual agonist, in a translational mouse model of non-alcoholic steatohepatitis

Body weight loss of ≥ 10% improves the metabolic derangements and liver disease in the majority of non-alcoholic steatohepatitis (NASH) patients, suggesting metabolic modulators may be effective in controlling disease. The pharmacodynamics of ALT-801, a GLP-1/glucagon receptor dual agonist optimized for NASH and weight loss, were compared to semaglutide (GLP-1 receptor agonist) and elafibranor (peroxisome proliferator-activated receptor, PPAR-α/δ, agonist) in a biopsy-confirmed, diet-induced obese (DIO) mouse model of NASH (DIO-NASH). Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks. Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet. Study endpoints included body and liver weight, liver and plasma total cholesterol and triglycerides, plasma aminotransferases, histological analysis of liver steatosis, inflammation (galectin-3) and fibrosis (collagen type 1 alpha 1), and evaluation of individual animal changes in composite Non-alcoholic Fatty Liver Disease Activity Score (NAS), and fibrosis stage. ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor. ALT-801 significantly reduced the inflammation marker galectin-3 and the fibrosis marker collagen type 1 alpha 1 vs. vehicle (p < 0.05), with ALT-801 producing greater reductions in galectin-3 vs. elafibranor (p < 0.05). Importantly, all animals treated with ALT-801 significantly improved composite NAS compared to the active controls. This study provides evidence for a potential role for ALT-801 in the therapeutic treatment of NASH.

Desempenho, qualidade da carne e lipidemia de codornas de corte alimentadas com rações contendo óleos essenciais

ABSTRACT: This study evaluated the effect of essential oil (ESOL) of Mentha piperita and Melaleuca alternifolia on meat-type quails. To examine performance, a completely randomized design was used, with four treatments and eight repetitions each, using seven birds per repetition. To assess lipidemia, a completely randomized design in a 4 × 2 factorial scheme was used, with four treatments and two collection conditions using eight repetitions and one bird per repetition. Weight gain, feed intake, feed conversion, carcass yield, cholesterol, high-density lipoporteins, triglycerides, pH, and brightness of quail breast meat were assessed. The data were analyzed for homoscedasticity and normality, and the means were subjected to analysis of variance. Adding M. piperita and M. alternifolia ESOL to the diets of meat-type quails can improve performance, carcass yield, and meat quality characteristics, comparable to the use of performance-enhancing antibiotics. The use of zinc bacitracin, M. piperita, and M. alternifolia under different collection conditions did not increase the serum levels of low-density and very low-density lipoproteins. The variation coefficients measured after 12 hours of fasting were 86% lower than without fasting.

Should we really avoid fat in diet? The beneficial effects of low carbohydrate diet versus low fat diet on cardiovascular health: a systematic review and meta-analysis

Abstract Background European Society of Cardiology and the American College of cardiology recommend a diet that is considerably low in fat (&amp;lt;35%) and high in carbohydrates (45–55%) for cardiovascular disease (CVD) prevention. However, recent evidence suggests that low-carbohydrate diets (LCD) can provide similar, if not, better CVD protection. Design Systematic review and meta-analysis Methods 3 databases were screened until 17th of August 2020 for randomized controlled trials (RCTs). Two investigators selected studies, extracted data, and assessed risk of bias. Certainty of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Weighted mean differences and 95% confidence intervals were calculated. Results 25 trials with a total of 2438 patients were included. LCD resulted in greater reductions in body weight (WMD −1.93 (95% CI −2.69, −1.16) kg; p&amp;lt;0.0001), triglycerides (WMD −26.13 (95% CI −23.45, −14.29) mg/dL; p&amp;lt;0.0001), TNF-alpha (WMD −0.5 (95% CI −0.82, −0.17) pg/mL; p=0.003) and IL-6 (95% CI −2.29, −0.59) pg/mL; p=0.0009) with a greater increase in HDL-C (WMD 3.73 (95% CI 2.92, 4.54) mg/dL; p&amp;lt;0.ehab724.24271) and LDL-C (WMD 5.07 (95% 1.9, 8.23) mg/dL; p=0.002) compared to low fat diet (LFD). There was no statistical difference in systolic (WMD 0.5 (95% CI −1.06, 2.05) mmHg; p=0.53) and diastolic blood pressure reduction (WMD −0.22 (95% CI −1.35, 0.91) mmHg; p=0.70). Conclusions Obese patients with other cardiovascular risk factors assigned to an LCD achieved greater reductions in weight loss and triglycerides levels with a greater increase in HDL-C levels and a more pronounced anti-inflammatory state than patients assigned to an LFD. Hence, low carbohydrate diets could be an alternative tool for cardiovascular protection in selected patients. Funding Acknowledgement Type of funding sources: None.

Prevalence Rate and Correlation Between Triglyceride Level and Human Body Mass Index in Sulaimani Province, Iraq

The condition of elevated concentrations of ‎triglyceride in ‎the blood is called hypertriglyceridemia, which ‎triggers the onset of some physiological disorder. This study was carried out to find the ‎correlation between body weight and ‎hypertriglyceridemia. ‎Out of 518 cases, 342 individuals were underweight, with body ‎mass index (BMI) values of ≤18, while their mean ‎serum triglyceride level was 172.4 ± 25.2mg/dl. In addition, 99 cases had normal BMI of &gt;18, whereas 60 were overweight (‎BMI = 25-29), with mean serum triglyceride level of 182.3 ± 15.9. Also, 17 cases were obese (BMI &gt;30), where the ‎mean triglyceride level was 202 ± 25.6. The results showed no significant differences in terms of weight categories and triglyceride levels, whereas significant ‎effects of marital status, daily exercise, and diet on elevated triglyceride ‎levels were observed. These findings conclude that underweight and ‎normal BMI individuals were as much at risk of elevated level of triglyceride as overweight and obese ones, which are mostly at higher risk. Moreover, daily exercise and supplementary nutrient have significant effects on triglyceride level.

Diet-induced prediabetes: effects of exercise treatment on risk factors for cardiovascular complications

BackgroundAn animal model of prediabetes that has been developed in our laboratory using a high fat high carbohydrate diet and lack of physical activity displays risk factors for cardiovascular complications. The effect of exercise against these risk factors in this animal model remains unknown. Therefore, we evaluated the effect of intermittent and regular exercise treatment on the risk factors for cardiovascular complications in this animal model of prediabetes.MethodsFollowing prediabetes induction, animals were randomly assigned to the following groups (n = 6): non-diabetic, prediabetic, intermittently exercising prediabetic and regularly exercising prediabetic. Exercise exposure was 7 weeks long. Body weight changes, caloric intake, blood glucose, total cholesterol, and triglyceride concentration was measured after 20 and 29 weeks while blood pressure was only measured after 29 weeks. Plasma endothelial nitric oxide synthase, malonaldehyde, glutathione peroxidase, tumour necrosis factor-alpha and C-reactive protein concentration from the heart were measured 2 weeks post-exercise termination (week 30).ResultsWe found increased body weight, caloric intake and mean arterial pressure in the prediabetic group by comparison to the non-prediabetic group. The same trend was observed in blood glucose and triglyceride concentrations. However, all of these parameters were reduced in the intermittently exercising prediabetic and regularly exercising prediabetic groups. This reduction was further accompanied by a decrease in the endothelial nitric oxide synthase, tumour necrosis factor-alpha and C-reactive protein concentration with improved oxidative stress biomarkers.ConclusionsThe progression of pre-diabetes to diabetes is slowed or possibly stopped by exercise (regular or intermittent). Additionally, biomarker profiles indicative of cardiovascular disease in pre-diabetics are improved by exercise.

Combined extracts of Moringa oleifera, Murraya koeingii leaves, and Curcuma longa rhizome increases energy expenditure and controls obesity in high-fat diet-fed rats

BackgroundLI85008F is a proprietary combination of leaf extracts of Moringa oleifera, Murraya koeingii, and extract of Curcuma longa rhizome. This herbal extract combination is an effective weight loss supplement for overweight and obese subjects. The present study aimed to investigate the thermogenic potential of the LI85008F in high-fat diet (HFD)-induced obese Sprague Dawley rats.MethodsSeven rats received a regular diet (RD), and twenty-one rats received a high-fat diet (HFD) for 56 days. On day 28, the HFD-fed rats were randomized into three groups (n = 7). Starting from day 29 through day 56, one HFD-fed group received daily oral gavage of 0.5% Carboxymethylcellulose Sodium (CMC) alone (HFD), and the remaining two groups received 100 and 250 mg/kg LI85008F (LI85008F-100 and LI85008F-250, respectively).Body weight, fat mass, fat cell size, liver weight, liver triglyceride were measured. The energy metabolism parameters were measured using indirect calorimetry. In serum, the metabolic and endocrine markers were analyzed. The adipogenic and thermoregulatory proteins expression in the white adipose tissue (WAT) were analyzed using an immunoblot assay.ResultsSupplementation with both doses of LI85008F significantly increased resting energy expenditure (REE) in the obese rats. The LI85008F-250 rats showed significant up-regulation of uncoupling protein-1 (UCP-1) expression, as compared with the HFD rats. LI85008F significantly reduced body weight gain, fat mass, fat cell size, liver weight, and hepatic triglycerides. Serum triglyceride, total cholesterol, glucose, leptin, and fat cell markers were significantly reduced in LI85008F-supplemented rats compared to the HFD rats.ConclusionThe present data suggest that LI85008F reduces body fat mass and controls body weight gain via increasing energy metabolism in combination with reduced lipogenesis in diet-fed obese rats.

Matrix Metalloproteinases in Obesity After Gastric Bypass Surgery—an Experimental Study

Matrix metalloproteinases (MMPs) are enzymes involved in the modulation of extracellular matrix (ECM) and adipocytes and preadipocyte differentiation. The pathophysiology of obesity has characterized by many cellular and molecular processes such as inflammatory processes, macrophage infiltration of adipose tissue, and remodeling of ECM via MMP. The purpose of the study was to determine if we can consider MMPs as a marker of effectiveness in bariatric surgery and if sulodexide administration pre- and postoperative has a benefit in terms of tissue remodeling of weight loss. An experimental study has performed using 40 obese Wistar rats (10 rats in the control group and 30 obese rats in study groups). Those in the study group were divided into three groups and underwent gastric bypass (B group), sulodexide administration (S group), gastric bypass, and sulodexide administration (BS group). Sulodexide was administered because of its antithrombotic effect in the procoagulant status of obese subjects. The pre- and postoperative weight, glucose level, cholesterol, triglycerides, MMP-2, and MMP-9 were analyzed. We compared the results to see if bariatric surgery modifies the MMPs status and if there is a correlation between the weight loss and the other parameters and also if sulodexide has any contribution to the results. The MMP-2 and MMP-9 activities were detectable, but MMP-2 was significantly higher than MMP-9. MMP-2 correlates with body weight parameters before surgery and after surgery, after significant bodyweight reduction as a result of bariatric surgery (r = 0.478, p = 0.017). There is a strong correlation between the weight loss, glucose level, and cholesterol and the values of MMP-2 (r = 0.92, p = 0.022, respectively, r = 0.759, p = 0.033). MMP-9 is correlated with weight loss and triglycerides level. But it was not as sensitive as MMP-2. Sulodexide administration in group S had a positive influence on the MMP-2 and MMP-9 compared with the values of groups B and C but without statistical significance. MMP-2 and MMP-9 are the two most important ECM enzymes involved in adipose tissue remodeling after bariatric surgery. The correlations between cholesterol, triglycerides, glucose, weight loss, excess weight, and body mass index (BMI) parameters and MMPs level demonstrate the direct relationship of these enzymes in obesity. Although we believe that more in-depth studies are required, MMPs may be considered a marker of the effectiveness of bariatric surgery.

Ganoderma lucidum culture supplement ameliorates dyslipidemia and reduces visceral fat accumulation in type 2 diabetic rats

ABSTRACT Diabetic rats were daily fed with a high-cholesterol diet containing 1% or 3% freeze-dried whole submerged G. lucidum culture or its mycelia for 5 weeks. Body weight, adipose tissue weight and plasma triglyceride levels were reduced, while high-density lipoprotein-cholesterol levels were elevated in rats fed with G. lucidum powder supplement diets. Notably, G. lucidum supplements downregulated the activities of hepatic acetyl-CoA carboxylase, fatty acid synthase and lipoprotein lipase, but upregulated the activity of hormone-sensitive lipase in the perirenal adipose tissues. Moreover, G. lucidum supplements increased the faecal triglyceride excretion. Therefore, daily supplementation of submerged G. lucidum culture, especially mycelia, can ameliorate dyslipidemia and reduce visceral fat accumulation in diabetic rats fed with a high-fat diet, which is closely related to the modulation of lipid synthesis, metabolism, and excretion.

Effect of Dietary Supplementation of Sea Buckthorn Leaf Meal in Coloured Breeder and Their Post Hatch Chicks on Growth Performance and Serum Biochemical Attributes During Summer Season

The present experiment was conducted to study the effect of dietary supplementation of sea buckthorn leaf meal (SBTLM) in breeder chicken and their post hatch growth performance and serum biochemical attributes during summer season. Ninety coloured Chabro breeder hens and eighteen viable cocks in 1:5 sex ratio were randomly distributed into three treatment groups: Control (Basal), standard breeder diet (BB); basal+0.5% and basal+1.0% SBTLM. Thereafter, ninety chicks from each breeder groups were further subdivided into three groups: Control (Basal), Broiler starter till 4 weeks, broiler finisher till 8 weeks of age, (BP); basal+0.5% supplementation and basal+1.0% supplementation of SBTLM. The weekly body weight gain (g) was significantly higher (plessthan0.05) in 0.5% SBTLM supplemented breeder group during 0-4 week and significantly higher plessthan0.01) in 0.5% SBTLM supplemented post hatch group during 0-8 week of the study period. Similarly, weekly FCR were also significantly better (plessthan0.05) in 0.5% SBTLM supplemented breeder group during 0-4 week and significantly higher (plessthan0.01) in 0.5% SBTLM supplemented post hatch group during 0-8 week of the study period. Serum HDL was significantly higher (plessthan0.05), where as serum cholesterol was significantly lower (plessthan0.05) and serum triglyceride was significantly lower plessthan0.01) in both post hatch SBTLM supplemented groups as compared to control group. No significant difference were observed in other serum biochemical attributes viz. total protein, albumin, globulin, A/G ratio, uric acid, creatinine, SGOT, SGPT and ALP among the treatment groups. Thus, it may be concluded that dietary supplementation of sea buckthorn leaf meal in coloured chicken @ 0.5% resulted in higher phase wise body weight gain, FCR, serum HDL, lower cholesterol and triglyceride without any adverse effect on other biochemical attributes.

2076-P: Time Restricted Eating (TRE) Promotes Weight Loss, Alters Body Composition, and Improves Metabolic Parameters in Overweight Humans

TRE, restriction of the eating window, reduces weight in animals and humans. We performed a randomized clinical trial examining the effect of TRE on body composition and glycemic measures in overweight humans without diabetes. We hypothesized that TRE will reduce weight and alter body composition compared with unrestricted feeding (non-TRE). 21 overweight subjects [18F/3M, mean(SE), age: 44.7 years (2.7), BMI:34.6 kg/m2(1.7) with a prolonged eating window:15.6 hours (0.2)] were randomized to either 12 weeks of TRE [n=11 (goal 8 hours)] or non-TRE [n=10]. All oral intake was logged using the myCircadianClock smart phone application to remotely monitor TRE adherence. Subjects also underwent: 2-hour oral glucose tolerance test, 2-week continuous glucose monitoring (Freestyle Libre), and 2-week activity tracking (Actigraph Link) pre and post intervention. Compared with the non-TRE group [eating window 15.2 hours (0.3)] post-intervention, the TRE group [eating window 10.4 hours (0.6)] decreased weight [-3.6 kg(0.6) vs. -1.4 kg(0.7)], visceral fat [-260 g(110) vs. 38 g(56)], lean mass [-1450 g(389) vs. -95.5 g(351)] and triglycerides [-23.6%(6.8) vs. -0.57%(7.6)] (all p≤0.05). Relative to baseline, the TRE group decreased: weight, fasting glucose, fat mass, lean mass, visceral fat, and fasting triglyceride levels (all p&amp;lt;0.05). This was not observed in the non-TRE group. TRE-related weight loss was associated with lower: fat mass [-4%(0.9)], visceral fat [-11%(4.0)], and lean mass [-3%(0.8)] relative to baseline (all p&amp;lt;0.05). All TRE-related effects were not significant after adjusting for weight loss. Neither intervention significantly altered physical activity. In overweight subjects, TRE reduced weight and improved metabolic parameters (triglycerides, fasting glucose). However, the TRE-related weight loss included both lean and fat mass loss. Further investigation into the translational aspects of TRE to treat obesity-related disorders is warranted. Disclosure L.S. Chow: Research Support; Self; Eli Lilly and Company. E. Manoogian: None. A.C. Alvear: None. Q. Wang: None. S. Panda: Other Relationship; Self; PenguinRandomHouse. D.G. Mashek: Consultant; Self; Eli Lilly and Company. Research Support; Self; Eli Lilly and Company. Funding University of Minnesota Healthy Foods Healthy Lives (17SFR-2YR50LC)

The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and NASH when fed a Western diet supplemented with fructose

BackgroundMetabolic disorders such as insulin resistance, obesity, and hyperglycemia are prominent risk factors for the development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH). Dietary rodent models employ high fat, high cholesterol, high fructose, methionine/choline deficient diets or combinations of these to induce NAFLD/NASH. The FATZO mice spontaneously develop the above metabolic disorders and type 2 diabetes (T2D) when fed with a normal chow diet. The aim of the present study was to determine if FATZO mice fed a high fat and fructose diet would exacerbate the progression of NAFLD/NASH.MethodsMale FATZO mice at the age of 8 weeks were fed with high fat Western diet (D12079B) supplemented with 5% fructose in the drinking water (WDF) for the duration of 20 weeks. The body weight, whole body fat content, serum lipid profiles and liver function markers were examined monthly along with the assessment of liver histology for the development of NASH. In addition, the effects of obeticholic acid (OCA, 30 mg/kg, QD) on improvement of NASH progression in the model were evaluated.ResultsCompared to normal control diet (CD), FATZO mice fed with WDF were heavier with higher body fat measured by qNMR, hypercholesterolemia and had progressive elevations in AST (~ 6 fold), ALT (~ 6 fold), liver over body weight (~ 2 fold) and liver triglyceride (TG) content (1.4–2.9 fold). Histological examination displayed evidence of NAFLD/NASH, including hepatic steatosis, lobular inflammation, ballooning and fibrosis in FATZO mice fed WDF. Treatment with OCA for 15 weeks in FATZO mice on WDF significantly alleviated hypercholesterolemia and elevation of AST/ALT, reduced liver weight and liver TG contents, attenuated hepatic ballooning, but did not affect body weight and blood TG levels.ConclusionWDF fed FATZO mice represent a new model for the study of progressive NAFLD/NASH with concurrent metabolic dysregulation.

Effects of Laparoscopic Sleeve Gastrectomy on Insulin Secretion Patterns in Young Obese Patients with Acanthosis Nigricans

Background: Acanthosis nigricans (AN) is a skin condition commonly often accompanied by insulin resistance and hyperinsulinemia. Patients with AN are prone to diabetes, especially in young obesity. Metformin were usually used to treat these patients. However, reports about the effectiveness of LSG surgery on young obese patients with AN are rare. Objective: The aim of our study was to evaluate the efficacy of LSG surgery on insulin secretion patterns and anthropometric variables for obese patients with AN. Methods: 30 young obese patients with AN were recruited for this study. Before and at 12 months after the LSG surgery, BMI and blood samples were collected. OGTT were used to evaluate the insulin level and its rhythm of secretion. AN extent and AN texture were determined according to the scale developed and validated. Results: For these patients, BMI decreased from 40.98±4.93 kg/m2 to 27.27±4.13 kg/m2 at 12 months after surgery. Along with weight loss, triglycerides and total cholesterol decreased significantly, and high-density lipoprotein cholesterol (HDL-C) increased significantly as of 12 months after surgery. But the change of low-density lipoprotein cholesterol (LDL-C) is not obvious. A significant decrease in insulin resistant (HOMA-IR) was observed. The insulin release curves showed hyperinsulinemia and abnormal rhythm of secretion before surgery. At 12 months after surgery the fasting, 2h postprandial insulin levels and the rhythm of insulin secretion were restored to normal level. But the insulin levels at 30min and 60min were higher than before surgery. The extent of AN for most patients were improved. Only 23.4% patients still were severe (vs. 59.3% before surgery). More than 50% patients were remission. Conclusion: In this study of LSG in obesity patients with AN, we found significant improvements in weight, dyslipidemia, hyperinsulinemia and AN extent. LSG will be a new effective therapeutic approach for young obesity patients with AN. Disclosure C. Qian: None. S. Qu: None. C. Zhu: None. J. Gao: None. F. Mei: None. L. Bu: None.

Exenatide Treatment Improves Mitochondrial Metabolism and Hepatic Insulin Sensitivity in Mice with Nonalcoholic Steatohepatitis (NASH)

Exenatide (Exe) is a glucagon-like peptide-1agonist (GLP-1) that enhances insulin production, slows gastric emptying and reduces appetite. Nonalcoholic fatty liver disease (NAFLD), and its more severe form known as NASH, are frequent complications of T2DM. As mitochondrial dysfunction and lipotoxicity are central features of NASH, we tested whether Exe improved mitochondrial oxidative function and hepatic insulin resistance in this setting. Mice (C57/BL6) were fed either a high-fructose, high trans-fat (TFD) diet for 24 weeks to induce NASH or a control diet. After 16 weeks, mice were randomly assigned for the final 8 weeks to subcutaneous Exe (30 µg/kg/day) or vehicle. After an overnight fast, mice received an i.v. infusion of [13C3] propionate and [3,4-13C2] glucose to evaluate mitochondrial metabolism by NMR-based 13C-isotopomer analysis. Targeted metabolic analysis of lipids was measured by LC-MS/MS. Exenatide reduced liver weight and intrahepatic triglyceride content (TFD: 287±23 vs. Exe: 198±27 mg/g liver, p=0.03). Fasting plasma glucose, insulin, FFA and TGs were all significantly lower with Exe. Expression of lipogenic genes and inflammatory markers were significantly lowered by Exe. Moreover, Exe reduced hepatic glucose production, TCA cycle flux, anaplerosis and pyruvate cycling. Exenatide administration improved the lipidomic profile, and decreased hepatic byproducts resulting from incomplete fat oxidation (typically associated with insulin resistance/lipotoxicity), such as diacylglycerols (TFD: 111±13 vs. Exe: 64±13 µmol/g protein, p=0.02) and ceramides (TFD: 1.6±0.1 vs. Exe: 1.3±0.1 µmol/g protein, p=0.02). Conclusion: In an animal model of NASH, Exe improves hepatic insulin sensitivity, mitochondrial TCA cycle flux and reduces toxic lipid metabolites resulting in an improvement of mitochondrial function. Taken together, these results suggest that Exe may be of clinical value in the management of NASH. Disclosure S. Kalavalapalli: None. F. Bril: None. A. Vergara: None. N. Sunny: None. K. Cusi: Consultant; Self; Janssen Global Services, LLC., Eli Lilly and Company. Research Support; Self; Cirius Therapeutics. Other Relationship; Self; Nordic Bioscience. Research Support; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc.. Other Relationship; Self; Quest Diagnostics. Research Support; Self; Zydus Pharmaceuticals (USA) Inc.. Other Relationship; Self; OWL metabolomics, Echosens. Research Support; Self; Janssen Global Services, LLC.. Consultant; Self; Tobira Therapeutics, Pfizer Inc..

Abstract 169: Lipoproteins and their Modified Forms Regulate Smooth Muscle Cell Calcification

Background: Vascular calcification (VC), alongside atherogenic lipoprotein profiles, have been correlated with poor cardiovascular outcome, however there is a paucity of literature exploring the relationship between the two regarding VC progression. We therefore aim to examine the roles of lipoprotein species and their oxidised forms on both medial and intimal VC. Methods: Human aortic smooth muscle cells (HAoSMC) were pre-treated with 200 μg/ml high (HDL), low (LDL) and very low (VLDL) density lipoproteins for 24 hours before treating cells with a calcification medium (CM; Ca 2.7mM, PO 4 2.0 mM). Cells were harvested using an alizarin red (ARS) calcification assay, or at various time points for qPCR analysis. In parallel, in vivo studies using apolipoprotein E knock-out mice were fed an atherogenic diet for 40 weeks and received reconstituted HDL (rHDL) infusions containing apoA-I (20mg/kg) and 1-palmitoyl-2-linoleoyl phosphatidylcholine during the final 4 weeks of the study. Tissues were harvested and stained for plaque assessment (H&amp;E) and calcium deposits (ARS). Results: Pre-treatment of HAoSMC with rHDL inhibited calcification (43.9%, p&lt;0.001), whereas ox-rHDL removed its protective effects. Likewise, ox-LDL (77.1%, p&lt;0.05) also upregulated calcium deposition and interestingly ox-VLDL significantly decreased calcification (70.5%, p&lt;0.05) with their native counterparts having no effects. PCR measures of calcification markers Runx2, RANKL and alkaline phosphatase show a time-dependent increase in expression as calcification occurs. In animal studies, no change in weight gain, cholesterol or triglyceride levels were observed with treatment. In addition, rHDL infusions did not alter plaque size however ARS staining of the brachiocephalic artery demonstrated a significant reduction (6.58%, p&lt;0.05) in calcification present in the atherosclerotic plaque. Conclusions: This study is the first to demonstrate the effects of lipoproteins on VC in vitro and the effects of rHDL on in vivo VC. Somewhat in accordance to the roles of lipoproteins in atherosclerosis, HDL and ox-VLDL show a reduction of calcification, where-as ox-LDL enhances calcification of HAoSMC.

Adherence to Mediterranean and low-fat diets among heart and lung transplant recipients: a randomized feasibility study

BackgroundHeart and lung transplant recipients are at a substantially increased risk of cardiovascular disease (CVD). Since both low-fat and Mediterranean diets can reduce CVD in immunocompetent people at high risk, we assessed adherence among thoracic transplant recipients allocated to one or other of these diets for 12 months.MethodsForty-one transplant recipients (20 heart; 21 lung) randomized to a Mediterranean or a low-fat diet for 12 months received diet-specific education at baseline. Adherence was primarily assessed by questionnaire: 14-point Mediterranean diet (score 0–14) and 9-point low-fat diet (score 0–16) respectively, high scores indicating greater adherence. Median scores at baseline, 6 months, 12 months, and 6-weeks post-intervention were compared by dietary group. We further assessed changes in weight, body mass index (BMI) and serum triglycerides from baseline to 12 months as an additional indicator of adherence.ResultsIn those randomized to a Mediterranean diet, median scores increased from 4 (range 1–9) at baseline, to 10 (range 6–14) at 6-months and were maintained at 12 months, and also at 6-weeks post-intervention (median 10, range 6–14). Body weight, BMI and serum triglycerides decreased over the 12-month intervention period (mean weight − 1.8 kg, BMI –0.5 kg/m2, triglycerides − 0.17 mmol/L). In the low-fat diet group, median scores were 11 (range 9–14) at baseline; slightly increased to 12 (range 9–16) at 6 months, and maintained at 12 months and 6 weeks post-intervention (median 12, range 8–15). Mean changes in weight, BMI and triglycerides were − 0.2 kg, 0.0 kg/m2 and − 0.44 mmol/L, respectively.ConclusionsThoracic transplant recipients adhered to Mediterranean and low-fat dietary interventions. The change from baseline eating habits was notable at 6 months; and this change was maintained at 12 months and 6 weeks post-intervention in both Mediterranean diet and low-fat diet groups. Dietary interventions based on comprehensive, well-supported education sessions targeted to both patients and their family members are crucial to success. Such nutritional strategies can help in the management of their substantial CVD risk.Trial registrationThe IRAS trial registry (ISRCTN63500150). Date of registration 27 July 2016. Retrospectively registered.

Can voluntary exercise improve renal changes in offspring induced by maternal obesity

Obesity in the mother is known to affect offspring, making them more prone to obesity, diabetes, and kidney disease. A recent study reported that children of obese mothers have a 22% increased risk of developing kidney disease suggesting that its development may be programmed in utero. However, the link between maternal obesity and offspring kidney disease remains unclear. Exercise is known to be beneficial in kidney disease, but whether it impacts renal effects of maternal obesity is not known. Thus we studied the impact of maternal obesity on siblings that were either sedentary or given access to a running wheel. Female Sprague‐Dawley rats were fed either chow diet or high‐fat diet (HFD) for 6 weeks before mating. Female offspring were weaned onto either chow diet or HFD and after 7 weeks, half of offspring were exercised for 5 weeks. Offspring were killed at 15 weeks; kidneys were collected for gene expression. The body weight, kidney mass, and kidney triglyceride levels were measured. Offspring of obese mothers had significantly increased body weight which was reduced by exercise in offspring consuming HFD. Kidney weight was significantly increased by maternal diet and post‐weaning HFD. Maternal diet was associated with a significant increase in kidney triglyceride accumulation; chow fed offspring of obese mother showed a 91% increase in renal triglyceride content (P&lt;0.001). Post‐weaning HFD consumption also increased kidney triglyceride content by 37% and 20% in offspring of lean and obese mothers, respectively (P&lt;0.01). However, exercise also increases renal triglyceride accumulation in offspring of both obese and lean mother consuming HFD. Lipid accumulation was associated with dysregulation of lipid metabolism genes. Maternal diet was associated with an upregulation of fatty acid transporter Cd36. Ldl receptor (Ldlr), involved in uptake of fat, was significantly upregulated by both post‐weaning HFD and exercise. Downregulation of renal lipoprotein lipase (Lpl) which is involved in hydrolyzing circulating triglyceride was observed by current HFD and upregulated by exercise. Sterol regulatory element binding protein 1 (Srebp 1) and acetyl‐CoA carboxylase alpha (Acaca), involve in lipogenesis, were upregulated by exercise. Significant upregulation of kidney injury molecule 1 (Kim 1) and neutrophil gelatinase‐associated lipocalin (Ngal) was also induced by post‐weaning HFD. Our data suggest that maternal diet has a greater effect than current HFD consumption on triglyceride accumulation in offspring kidney. Voluntary exercise in offspring did not reduce this triglyceride content in the kidney. Dysregulation of lipid metabolism genes may explain renal lipid accumulation which may further result in renal injury.Support or Funding InformationThis research was funded by a project grant from the National Health and Medical Research Council of Australia to M.J.M. S.S.C. was supported by University International Postgraduate Award of UNSW Australia.

Intact parathyroid hormone levels and primary hyperparathyroidism

ABSTRACTObjective: The aim of this article is to compare clinical characteristics and lab values for metabolic syndrome between primary hyperparathyroidism (PHPT) patients with different levels of serum intact parathyroid hormone (iPTH) and to determine correlation between different clinical characteristics among PHPT patients Methods: We reviewed charts of 212 PHPT patients in this retrospective study. Patients were divided into two groups according to their initial serum iPTH levels. Student’s t-tests were used to compare the two groups for differences in clinical characteristics and laboratory values. Pearson’s correlation coefficients were used to assess associations. Results: Of the 212 PHPT patients, 100 were classified as m-iPTH group (serum iPTH < 140 pg/mL), whereas 112 patients were defined as h-iPTH group (serum iPTH ≥ 140 pg/mL). The h-iPTH patients were younger, had higher serum calcium and alkaline phosphatase levels, but exhibited lower 25(OH)-vitamin D and HDL levels, when compared with those of m-iPTH patients. Adenoma weights in the h-iPTH group tended to be higher than that in the m-iPTH group. Furthermore, association studies revealed that the iPTH level was positively correlated with adenoma weight and serum calcium and triglyceride (TG) levels but negatively correlated with HDL level. Conclusion: Our study supports the hypothesis that iPTH level is associated with TG and HDL levels and should be a factor to consider in the management of PHPT patients.

Effect of neonatal overfeeding on associated enzymes of lipid metabolism in rat liver

Objective To investigate the effect of neonatal overfeeding on the expression of lipid metabolic associated enzymes and molecular mechanisms in the livers of rats. Methods Male Sprague-Dawley rats were randomly assigned to litter sizes of three group (small litters, SL group) or ten (normal litters, NL group) on postnatal day 3.Body weight, milk intake, liver and fat pad (epididymal and retroperitonea) weight, and hepatic histological analysis were recorded in week 2 and week 3, respectively.The levels of lipids were detected by the automatic biochemical analyzer.The mRNA expressions of acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), liver-type fatty acid-binding protein (L-FABP), carnitine palmitoyltransferase 1(CPT1), microsomal triglyceride transfer protein (MTP), sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator activated receptor α (PPARα)in liver were determined by real time PCR; the protein expressions of SREBP-1c and PPARα were determined by Western lot. Results As early as week 2, the body weight of rats in SL group began to elevate (t=-5.997, P<0.001) and food intake (t=-3.462, P=0.002) compared with the rats in NL group, and persistent to weaning (body weight: t=-17.019, P<0.001; food intake: t=-2.276, P=0.031). By the time of 3 weeks old, SL rats increased visceral fat pad [retroperitonea (t=-7.643, P<0.001), epididymal (t=5.997, P=0.001)], liver weight (t=-7.812, P<0.001), hepatosomatic index (t=-3.829, P=0.003) and serum triglyceride (TG) level (t=-2.703, P=0.022) compared with those of NL rats, as well as the level of hepatic ACC mRNA (t=-3.751, P=0.007), LPL (t=-2.721, P=0.017) and L-FABP mRNA (t=-2.521, P=0.026) .While CPT1 mRNA (t=-1.531, P=0.155) and MTP mRNA (t=-1.741, P=0.098) levels remained unchanged in both groups.Hepatic SREBP-1c mRNA expression increased in SL rats after 2 to 3 weeks (t=-2.836, P=0.016), paralleled with ACC and LPL mRNA expression; while the mRNA and protein expression of PPARα remained unchanged (t=-0.854, P=0.411). Conclusions Postnatal overfeeding can promote higher liver pad and dyslipidemia at the time of weaning.The process may be regulated by up-regulated expression of ACC, LPL and L-FABP.SREBP-1c may be participated in the regulation of ACC, a rate-limiting enzyme involved in lipogenesis. Key words: Nutritional programming; Liver; Lipid metabolism; Rat